Editorial

3 pages, 175 KiB

Open AccessEditorial

Editorial of the Special Issue Titled “Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases”

by Nikolaos P. E. Kadoglou

Pharmaceuticals 2024, 17(4), 417; https://doi.org/10.3390/ph17040417 - 26 Mar 2024

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Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, with high social–economic costs [...] Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

Research

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16 pages, 1654 KiB

Open AccessArticle

Hemodynamic and Rhythmologic Effects of Push-Dose Landiolol in Critical Care—A Retrospective Cross-Sectional Study

by Sebastian Schnaubelt, Felix Eibensteiner, Julia Oppenauer, Daniel Tihanyi, Marco Neymayer, Roman Brock, Andrea Kornfehl, Christoph Veigl, Valentin Al Jalali, Sonja Anders, Barbara Steinlechner, Hans Domanovits and Patrick Sulzgruber

Pharmaceuticals 2023, 16(2), 134; https://doi.org/10.3390/ph16020134 - 17 Jan 2023

Cited by 3 | Viewed by 1954

Abstract

Background: The highly β1-selective beta-blocker Landiolol is known to facilitate efficient and safe rate control in non-compensatory tachycardia or dysrhythmia when administered continuously. However, efficacy and safety data of the also-available bolus formulation in critically ill patients are scarce. Methods: We conducted a [...] Read more.

Background: The highly β1-selective beta-blocker Landiolol is known to facilitate efficient and safe rate control in non-compensatory tachycardia or dysrhythmia when administered continuously. However, efficacy and safety data of the also-available bolus formulation in critically ill patients are scarce. Methods: We conducted a retrospective cross-sectional study on a real-life cohort of critical care patients, who had been treated with push-dose Landiolol due to sudden-onset non-compensatory supraventricular tachycardia. Continuous hemodynamic data had been acquired via invasive blood pressure monitoring. Results: Thirty patients and 49 bolus applications were analyzed. Successful heart rate control was accomplished in 20 (41%) cases, rhythm control was achieved in 13 (27%) episodes, and 16 (33%) applications showed no effect. Overall, the heart rate was significantly lower (145 (130–150) vs. 105 (100–125) bpm, p < 0.001) in a 90 min post-application observational period in all subgroups. The median changes in blood pressure after the bolus application did not reach clinical significance. Compared with the ventilation settings before the bolus application, the respiratory settings including the required FiO₂ after the bolus application did not differ significantly. No serious adverse events were seen. Conclusions: Push-dose Landiolol was safe and effective in critically ill ICU patients. No clinically relevant impact on blood pressure was noted. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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12 pages, 1657 KiB

Open AccessCommunication

Vascular Effects of the Fetal Hemoglobin Inducer Agent 3-(1,3-Dioxoisoindolin-2-yl) Benzyl Nitrate

by Barbara Terroni, Luis Henrique Oliveira de Moraes, Aline Renata Pavan, Gerson Jhonatan Rodrigues and Jean Leandro Dos Santos

Pharmaceuticals 2022, 15(11), 1311; https://doi.org/10.3390/ph15111311 - 24 Oct 2022

Viewed by 1148

Abstract

Vascular endothelium is a protective layer of cells lining the lumen of blood vessels that plays important roles by releasing factors responsible for controlling the vascular tone, regulating the expression of pro-inflammatory cytokines, and expressing adhesion molecules involved in vascular hemostasis. Imbalance of [...] Read more.

Vascular endothelium is a protective layer of cells lining the lumen of blood vessels that plays important roles by releasing factors responsible for controlling the vascular tone, regulating the expression of pro-inflammatory cytokines, and expressing adhesion molecules involved in vascular hemostasis. Imbalance of vascular properties leads to endothelial dysfunction (ED) and cardiovascular damage. Some diseases, such as sickle cell anemia, are characterized by ED with reduction in the levels of nitric oxide (NO). Previously, we have shown that the fetal hemoglobin inducer agent 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate (Lapdesf-4c) could act as NO donor, inhibiting platelet aggregation and reducing the inflammation associated with SCA. However, the vascular effect of this compound was not yet studied. Herein, we evaluated the effects of Lapdesf-4c in vascular reactivity experiments using aortic rings from male Wistar rats (300 g/90 days). We have found that Lapdesf-4c induced vasodilation in the presence (E+) or absence of endothelium (E−) with an average of EMax values of 101.8 ± 3.33% and 111.8 ± 3.21%. The mechanism of action was studied using 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), L-N^G-nitroarginine methyl ester (L-NAME), and hydroxocobalamin. The EMax values for those pathways were hydroxocobalamin (30.6 ± 2.21%), ODQ (4.75 ± 0.51%), and L-NAME (109 ± 3.65), suggesting that Lapdesf-4c exhibits NO-dependent mechanisms. Lapdesf-4c was able to prevent angiotensin-induced ED after incubation of aorta rings for 1 h. We found based on the concentration–effect curve using acetylcholine (ACh) that pEC50 values for the control, Ang II, and combination of (Ang II + Lapdesf-4c) were 6.73, 6.46, and 7.15, respectively. In conclusion, Lapdesf-4c has emerged as a new drug candidate that can promote vasodilation and act as a protective agent against ED, being useful to prevent vascular damage. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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16 pages, 2712 KiB

Open AccessArticle

Citicoline Modifies the Expression of Specific miRNAs Related to Cardioprotection in Patients with ST-Segment Elevation Myocardial Infarction Subjected to Coronary Angioplasty

by Alejandro Silva-Palacios, Miguel Arroyo-Campuzano, Mirthala Flores-García, Mariana Patlán, Adrián Hernández-Díazcouder, Diego Alcántara, Ixchel Ramírez-Camacho, Dana Arana-Hidalgo, Elizabeth Soria-Castro, Fausto Sánchez, Héctor González-Pacheco and Cecilia Zazueta

Pharmaceuticals 2022, 15(8), 925; https://doi.org/10.3390/ph15080925 - 27 Jul 2022

Cited by 6 | Viewed by 1702

Abstract

Extracellular vesicles are recognized as signaling mediators between cells both in physiological and pathological communication. In this work, we explored the potential effect of citicoline to modify relevant proteins or miRNAs for cardioprotection in the smallest population of such microvesicles; i.e., in exosomes [...] Read more.

Extracellular vesicles are recognized as signaling mediators between cells both in physiological and pathological communication. In this work, we explored the potential effect of citicoline to modify relevant proteins or miRNAs for cardioprotection in the smallest population of such microvesicles; i.e., in exosomes from patients diagnosed with ST-segment elevation myocardial infarction (STEMI) undergoing coronary angioplasty. The plasma-exosome-enriched fraction from these patients was characterized. Their cellular origin was assessed by flow cytometry and Western blot, whereas miRNA expression was evaluated by real-time polymerase chain reaction (qRT-PCR). The content of caveolin-1, caveolin-3, and hnRNPA2B1, which play a relevant role in selective transport of miRNAs into microvesicles, along with the effect on cell viability of the exosomes obtained from citicoline-treated and untreated groups were also analyzed. Our results showed that hypoxic stress increases exosome release into the circulation. Moreover, we found that CD146+ increased in exosomes from citicoline-treated patients, while CD142+ decreased in these patients compared to the placebo group. No changes were detected in the protein levels of caveolin-1, caveolin-3, and hnRNPA2B1. Citicoline administration modified the expression of miR233-3p, miR92, and miR21-5p in exosomes. Cell viability decreased in the presence of exosomes from infarcted patients, while incubation of H9c2 cells with exosomes from patients reperfused with citicoline did not affect cell viability. In conclusion, citicoline administration modifies the expression of specific miRNAs related to cardioprotection in exosomes. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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13 pages, 1197 KiB

Open AccessArticle

The Role of Interventional Irisin on Heart Molecular Physiology

by Foad Alzoughool, Mohammad Borhan Al-Zghoul, Bayan Y. Ghanim, Michael Gollob, Nasir Idkaidek and Nidal A. Qinna

Pharmaceuticals 2022, 15(7), 863; https://doi.org/10.3390/ph15070863 - 14 Jul 2022

Cited by 3 | Viewed by 2118

Abstract

Irisin, encoded by the FNDC5 (fibronectin type III domain containing 5) gene, is a novel myokine that has been implicated as an essential mediator of exercise benefits. Effects of irisin on heart physiology is still ambiguous. This study aimed to evaluate the impact [...] Read more.

Irisin, encoded by the FNDC5 (fibronectin type III domain containing 5) gene, is a novel myokine that has been implicated as an essential mediator of exercise benefits. Effects of irisin on heart physiology is still ambiguous. This study aimed to evaluate the impact of exogenous administration of irisin on heart physiology and the pharmacokinetic profile of pump-administered irisin. To do so, Sprague Dawley rats were implanted with an irisin-loaded osmotic pump (5 μg/kg/day) for 42 days, and other animals were administered with single bolus subcutaneous injections of irisin (5 µg/kg). Body weights and blood samples were collected weekly for 42 days for serum irisin quantification and histopathology. Clinical biochemistry analyses were performed. Heart mRNA expression was assessed in 26 selected genes. Chronic interventional exogenous irisin significantly reduced body weight without affecting the heart myocyte size and significantly reduced creatine kinase enzyme level. Blood CBC, serum biochemistry, and heart morphology were normal. Gene expression of FNCD5, Raf1, CPT1, IGF-1, and CALCIN, encoding for heart physiology, increased while PGC1, Nox4, and Mfn1 significantly decreased. Nevertheless, irisin increased the expression of cardioprotective genes and inhibited some genes that harm heart physiology. Administration of irisin promotes myocardial functions and could be translated into clinical settings after preclinical profiling. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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10 pages, 786 KiB

Open AccessArticle

Impact of PCSK9 Inhibition on Proinflammatory Cytokines and Matrix Metalloproteinases Release in Patients with Mixed Hyperlipidemia and Vulnerable Atherosclerotic Plaque

by Marcin Basiak, Michal Kosowski, Marcin Hachula and Boguslaw Okopien

Pharmaceuticals 2022, 15(7), 802; https://doi.org/10.3390/ph15070802 - 27 Jun 2022

Cited by 12 | Viewed by 1614

Abstract

Atherosclerosis is a disorder in which, in addition to high cholesterol levels, several plasma factors play a significant role in its development. Among these cytokines and molecules are interleukin 6 (IL-6), interleukin 18 (IL-18), tumor necrosis factor α (TNF-α), metalloproteinase 2 (MMP-2), and [...] Read more.

Atherosclerosis is a disorder in which, in addition to high cholesterol levels, several plasma factors play a significant role in its development. Among these cytokines and molecules are interleukin 6 (IL-6), interleukin 18 (IL-18), tumor necrosis factor α (TNF-α), metalloproteinase 2 (MMP-2), and metalloproteinase 9 (MMP-9), all of which may contribute to the stabilization of atherosclerotic plaque. The purpose of this study was to determine the effect of advanced lipid-lowering therapy on the levels of these determinants by utilizing proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors in patients with verified high-risk atherosclerotic plaque. Methods: The study involved patients with dyslipidemia who had the presence of unstable atherosclerotic plaque verified by ultrasonography and who were eligible to begin alirocumab treatment. The levels of IL-6, IL, 18, TNF-α, and MMPs were determined in this group before and after three months of therapy. After treatment, a statistically significant decrease in concentrations of Il-18, Il-6, TNF-α (p < 0.001) and MMP-2 (p < 0.05) was observed. Additionally, we observed that the concentrations of these markers were significantly higher in the group of patients prior to initiating therapy than in the control group. Our study’s results suggest that PCSK-9 inhibitor therapy significantly reduces the concentration of factors influencing the stability of atherosclerotic plaque, which may explain their essential importance in reducing cardiovascular risk in patients receiving this treatment. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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11 pages, 19798 KiB

Open AccessArticle

A Selective Inhibitor of Cardiac Troponin I Phosphorylation by Delta Protein Kinase C (δPKC) as a Treatment for Ischemia-Reperfusion Injury

by Nir Qvit, Amanda J. Lin, Aly Elezaby, Nicolai P. Ostberg, Juliane C. Campos, Julio C. B. Ferreira and Daria Mochly-Rosen

Pharmaceuticals 2022, 15(3), 271; https://doi.org/10.3390/ph15030271 - 22 Feb 2022

Cited by 5 | Viewed by 4247

Abstract

Myocardial infarction is the leading cause of cardiovascular mortality, with myocardial injury occurring during ischemia and subsequent reperfusion (IR). We previously showed that the inhibition of protein kinase C delta (δPKC) with a pan-inhibitor (δV1-1) mitigates myocardial injury and improves mitochondrial function in [...] Read more.

Myocardial infarction is the leading cause of cardiovascular mortality, with myocardial injury occurring during ischemia and subsequent reperfusion (IR). We previously showed that the inhibition of protein kinase C delta (δPKC) with a pan-inhibitor (δV1-1) mitigates myocardial injury and improves mitochondrial function in animal models of IR, and in humans with acute myocardial infarction, when treated at the time of opening of the occluded blood vessel, at reperfusion. Cardiac troponin I (cTnI), a key sarcomeric protein in cardiomyocyte contraction, is phosphorylated by δPKC during reperfusion. Here, we describe a rationally-designed, selective, high-affinity, eight amino acid peptide that inhibits cTnI’s interaction with, and phosphorylation by, δPKC (ψTnI), and prevents tissue injury in a Langendorff model of myocardial infarction, ex vivo. Unexpectedly, we also found that this treatment attenuates IR-induced mitochondrial dysfunction. These data suggest that δPKC phosphorylation of cTnI is critical in IR injury, and that a cTnI/δPKC interaction inhibitor should be considered as a therapeutic target to reduce cardiac injury after myocardial infarction. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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13 pages, 723 KiB

Open AccessArticle

Apremilast Improves Endothelial Glycocalyx Integrity, Vascular and Left Ventricular Myocardial Function in Psoriasis

by Ignatios Ikonomidis, George Pavlidis, Nikolaos Kadoglou, George Makavos, Konstantinos Katogiannis, Aikaterini Kountouri, John Thymis, Gavriella Kostelli, Irini Kapniari, Konstantinos Theodoropoulos, John Parissis, Pelagia Katsimbri, Evangelia Papadavid and Vaia Lambadiari

Pharmaceuticals 2022, 15(2), 172; https://doi.org/10.3390/ph15020172 - 30 Jan 2022

Cited by 4 | Viewed by 3233

Abstract

The phosphodiesterase 4 inhibitor apremilast is used for the treatment of psoriasis. We investigated the effects of apremilast on endothelial glycocalyx, vascular and left ventricular (LV) myocardial function in psoriasis. One hundred and fifty psoriatic patients were randomized to apremilast (n = [...] Read more.

The phosphodiesterase 4 inhibitor apremilast is used for the treatment of psoriasis. We investigated the effects of apremilast on endothelial glycocalyx, vascular and left ventricular (LV) myocardial function in psoriasis. One hundred and fifty psoriatic patients were randomized to apremilast (n = 50), anti-tumor necrosis factor-α (etanercept; n = 50), or cyclosporine (n = 50). At baseline and 4 months post-treatment, we measured: (1) Perfused boundary region (PBR), a marker of glycocalyx integrity, in sublingual microvessels with diameter 5–25 μm using a Sidestream Dark Field camera (GlycoCheck). Increased PBR indicates damaged glycocalyx. Functional microvascular density, an index of microvascular perfusion, was also measured. (2) Pulse wave velocity (PWV-Complior) and (3) LV global longitudinal strain (GLS) using speckle-tracking echocardiography. Compared with baseline, PBR_{5–25 μm} decreased only after apremilast (−12% at 4 months, p < 0.05) whereas no significant changes in PBR_{5–25 μm} were observed after etanercept or cyclosporine treatment. Compared with etanercept and cyclosporine, apremilast resulted in a greater increase of functional microvascular density (+14% versus +1% versus −1%) and in a higher reduction of PWV. Apremilast showed a greater increase of GLS (+13.5% versus +7% versus +2%) than etanercept and cyclosporine (p < 0.05). In conclusion, apremilast restores glycocalyx integrity and confers a greater improvement of vascular and myocardial function compared with etanercept or cyclosporine after 4 months. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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14 pages, 2532 KiB

Open AccessArticle

A Novel Statin Compound from Monacolin J Produced Using CYP102A1-Catalyzed Regioselective C-Hydroxylation

by Ngoc Tan Cao, Ngoc Anh Nguyen, Chan Mi Park, Gun Su Cha, Ki Deok Park and Chul-Ho Yun

Pharmaceuticals 2021, 14(10), 981; https://doi.org/10.3390/ph14100981 - 26 Sep 2021

Cited by 4 | Viewed by 2147

Abstract

Statins inhibit the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), which is the rate-limiting enzyme in cholesterol biosynthesis. Statin therapy reduces morbidity and mortality in those who are at high risk of cardiovascular disease. Monacolin J is a statin compound, which is an intermediate in [...] Read more.

Statins inhibit the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), which is the rate-limiting enzyme in cholesterol biosynthesis. Statin therapy reduces morbidity and mortality in those who are at high risk of cardiovascular disease. Monacolin J is a statin compound, which is an intermediate in the lovastatin biosynthesis pathway, in the fungus Aspergillus terreus. It is also found in red yeast rice, which is made by culturing rice with the yeast Monascus purpureus. Monacolin J has a hydroxyl substituent at position C’-8 of monacolin L. Here, a new statin derivative from monacolin J was made through the catalysis of CYP102A1 from Bacillus megaterium. A set of CYP102A1 mutants of monacolin J hydroxylation with high catalytic activity was screened. The major hydroxylated product was C-6′a-hydroxymethyl monacolin J, whose structure was confirmed using LC–MS and NMR analysis. The C-6′a-hydroxymethyl monacolin J has never been reported before. It showed a greater ability to inhibit HMG-CoA reductase than the monacolin J substrate itself. Human liver microsomes and human CYP3A4 also showed the ability to catalyze monacolin J in producing the same product of the CYP102A1-catalyzed reaction. This result motivates a new strategy for the development of a lead for the enzymatic and chemical processes to develop statin drug candidates. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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Review

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17 pages, 1056 KiB

Open AccessReview

Role of Trientine in Hypertrophic Cardiomyopathy: A Review of Mechanistic Aspects

by Fitri Fareez Ramli, Syed Alhafiz Syed Hashim, Betty Raman, Masliza Mahmod and Yusof Kamisah

Pharmaceuticals 2022, 15(9), 1145; https://doi.org/10.3390/ph15091145 - 14 Sep 2022

Cited by 7 | Viewed by 2075

Abstract

Abnormality in myocardial copper homeostasis is believed to contribute to the development of cardiomyopathy. Trientine, a copper-chelating drug used in the management of patients with Wilson’s disease, demonstrates beneficial effects in patients with hypertrophic cardiomyopathy. This review aims to present the updated development [...] Read more.

Abnormality in myocardial copper homeostasis is believed to contribute to the development of cardiomyopathy. Trientine, a copper-chelating drug used in the management of patients with Wilson’s disease, demonstrates beneficial effects in patients with hypertrophic cardiomyopathy. This review aims to present the updated development of the roles of trientine in hypertrophic cardiomyopathy. The drug has been demonstrated in animal studies to restore myocardial intracellular copper content. However, its mechanisms for improving the medical condition remain unclear. Thus, comprehending its mechanistic aspects in cardiomyopathy is crucial and could help to expedite future research. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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16 pages, 408 KiB

Open AccessReview

Looking beyond the Skin: Pathophysiology of Cardiovascular Comorbidity in Psoriasis and the Protective Role of Biologics

by Isabel Andújar, Juan V. Esplugues and Patricia García-Martínez

Pharmaceuticals 2022, 15(9), 1101; https://doi.org/10.3390/ph15091101 - 03 Sep 2022

Cited by 5 | Viewed by 2475

Abstract

Psoriasis is a chronic systemic inflammatory disease associated with a higher incidence of cardiovascular disease, especially in patients with moderate to severe psoriasis. It has been estimated that severe psoriasis confers a 25% increase in relative risk of cardiovascular disease, regardless of traditional [...] Read more.

Psoriasis is a chronic systemic inflammatory disease associated with a higher incidence of cardiovascular disease, especially in patients with moderate to severe psoriasis. It has been estimated that severe psoriasis confers a 25% increase in relative risk of cardiovascular disease, regardless of traditional risk factors. Although the underlying pathogenic mechanisms relating psoriasis to increased cardiovascular risk are not clear, atherosclerosis is emerging as a possible link between skin and vascular affection. The hypothesis that the inflammatory cascade activated in psoriasis contributes to the atherosclerotic process provides the underlying basis to suggest that an anti-inflammatory therapy that improved atherosclerosis would also reduce the risk of MACEs. In this sense, the introduction of biological drugs which specifically target cytokines implicated in the inflammatory cascade have increased the expectations of control over the cardiovascular comorbidity present in psoriasis patients, however, their role in vascular damage processes remains controversial. The aim of this paper is to review the mechanistic link between psoriasis and cardiovascular disease development, as well as analyzing which of the biological treatments could also reduce the cardiovascular risk in these patients, fueling a growing debate on the modification of the general algorithm of treatment. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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23 pages, 1250 KiB

Open AccessReview

Potential Pharmaceutical Applications of Quercetin in Cardiovascular Diseases

by Paraskevi Papakyriakopoulou, Nikolaos Velidakis, Elina Khattab, Georgia Valsami, Ioannis Korakianitis and Nikolaos PE Kadoglou

Pharmaceuticals 2022, 15(8), 1019; https://doi.org/10.3390/ph15081019 - 18 Aug 2022

Cited by 29 | Viewed by 4232

Abstract

Quercetin, as a member of flavonoids, has emerged as a potential therapeutic agent in cardiovascular diseases (CVDs) in recent decades. In this comprehensive literature review, our goal was a critical appraisal of the pathophysiological mechanisms of quercetin in relation to the classical cardiovascular [...] Read more.

Quercetin, as a member of flavonoids, has emerged as a potential therapeutic agent in cardiovascular diseases (CVDs) in recent decades. In this comprehensive literature review, our goal was a critical appraisal of the pathophysiological mechanisms of quercetin in relation to the classical cardiovascular risk factors (e.g., hyperlipidemia), atherosclerosis, etc. We also assessed experimental and clinical data about its potential application in CVDs. Experimental studies including both in vitro methods and in vivo animal models mainly outline the following effects of quercetin: (1) antihypertensive, (2) hypolipidemic, (3) hypoglycemic, (4) anti-atherosclerotic, and (5) cardioprotective (suppressed cardiotoxicity). From the clinical point of view, there are human studies and meta-analyses implicating its beneficial effects on glycemic and lipid parameters. In contrast, other human studies failed to demonstrate consistent favorable effects of quercetin on other cardiometabolic risk factors such as MS, obesity, and hypertension, underlying the need for further investigation. Analyzing the reason of this inconsistency, we identified significant drawbacks in the clinical trials’ design, while the absence of pharmacokinetic/pharmacodynamic tests prior to the studies attenuated the power of clinical results. Therefore, additional well-designed preclinical and clinical studies are required to examine the therapeutic mechanisms and clinical efficacy of quercetin in CVDs. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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21 pages, 555 KiB

Open AccessReview

Pharmaceutical Prevention and Management of Cardiotoxicity in Hematological Malignancies

by Anastasia Stella Perpinia, Nikolaos Kadoglou, Maria Vardaka, Georgios Gkortzolidis, Apostolos Karavidas, Theodoros Marinakis, Chrysostomi Papachrysostomou, Panagiotis Makaronis, Charikleia Vlachou, Marina Mantzourani, Dimitrios Farmakis and Konstantinos Konstantopoulos

Pharmaceuticals 2022, 15(8), 1007; https://doi.org/10.3390/ph15081007 - 16 Aug 2022

Cited by 4 | Viewed by 2473

Abstract

Modern treatment modalities in hematology have improved clinical outcomes of patients with hematological malignancies. Nevertheless, many new or conventional anticancer drugs affect the cardiovascular system, resulting in various cardiac disorders, including left ventricular dysfunction, heart failure, arterial hypertension, myocardial ischemia, cardiac rhythm disturbances, [...] Read more.

Modern treatment modalities in hematology have improved clinical outcomes of patients with hematological malignancies. Nevertheless, many new or conventional anticancer drugs affect the cardiovascular system, resulting in various cardiac disorders, including left ventricular dysfunction, heart failure, arterial hypertension, myocardial ischemia, cardiac rhythm disturbances, and QTc prolongation on electrocardiograms. As these complications may jeopardize the significantly improved outcome of modern anticancer therapies, it is crucial to become familiar with all aspects of cardiotoxicity and provide appropriate care promptly to these patients. In addition, established and new drugs contribute to primary and secondary cardiovascular diseases prevention. This review focuses on the clinical manifestations, preventive strategies, and pharmaceutical management of cardiotoxicity in patients with hematologic malignancies undergoing anticancer drug therapy or hematopoietic stem cell transplantation. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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19 pages, 2298 KiB

Open AccessReview

A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block

by Nikolaos P. E. Kadoglou, Chrystalla Panayiotou, Michail Vardas, Nikolaos Balaskas, Nikolaos G. Kostomitsopoulos, Alexandra K. Tsaroucha and Georgia Valsami

Pharmaceuticals 2022, 15(5), 538; https://doi.org/10.3390/ph15050538 - 27 Apr 2022

Cited by 9 | Viewed by 3207

Abstract

Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical [...] Read more.

Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical cardiovascular risk factors (e.g., diabetes mellitus, etc.). We also assessed their potential protective and/or therapeutic application in cardiovascular diseases (CVDs), based on experimental and clinical studies. Pre-clinical studies including in vitro tests or animal models have predominantly implicated the following effects of silymarin and its constituents: (1) antioxidant, (2) hypolipidemic, (3) hypoglycemic, (4) anti-hypertensive and (5) cardioprotective. On the other hand, a direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration seems weak based on scarce data. In clinical trials, the most important findings are improved (1) glycemic and (2) lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while (3) the anti-hypertensive effects of silibinin/silymarin seem very modest. Finally, the changes in clinical endpoints are not robust enough to draw a firm conclusion. There are significant limitations in clinical trial design, including the great variety in doses and cohorts, the underlying conditions, the small sample sizes, the short duration and the absence of pharmacokinetic/pharmacodynamic tests prior to study commitment. More data from well-designed and high-quality pre-clinical and clinical studies are required to firmly establish the clinical efficacy of silibinin/silymarin and its possible therapeutic application in cardiovascular diseases. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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22 pages, 1116 KiB

Open AccessReview

Repurposing Dimethyl Fumarate for Cardiovascular Diseases: Pharmacological Effects, Molecular Mechanisms, and Therapeutic Promise

by Shilu Deepa Thomas, Niraj Kumar Jha, Bassem Sadek and Shreesh Ojha

Pharmaceuticals 2022, 15(5), 497; https://doi.org/10.3390/ph15050497 - 19 Apr 2022

Cited by 8 | Viewed by 3321

Abstract

Dimethyl fumarate (DMF) is a small molecule that has been shown to assert potent in vivo immunoregulatory and anti-inflammatory therapeutic actions. The drug has been approved and is currently in use for treating multiple sclerosis and psoriasis in the USA and Europe. Since [...] Read more.

Dimethyl fumarate (DMF) is a small molecule that has been shown to assert potent in vivo immunoregulatory and anti-inflammatory therapeutic actions. The drug has been approved and is currently in use for treating multiple sclerosis and psoriasis in the USA and Europe. Since inflammatory reactions have been significantly implicated in the etiology and progression of diverse disease states, the pharmacological actions of DMF are presently being explored and generalized to other diseases where inflammation needs to be suppressed and immunoregulation is desirable, either as a monotherapeutic agent or as an adjuvant. In this review, we focus on DMF, and present an overview of its mechanism of action while briefly discussing its pharmacokinetic profile. We further discuss in detail its pharmacological uses and highlight its potential applications in the treatment of cardiovascular diseases. DMF, with its unique combination of anti-inflammatory and vasculoprotective effects, has the potential to be repurposed as a therapeutic agent in patients with atherosclerotic cardiovascular disease. The clinical studies mentioned in this review with respect to the beneficial effects of DMF in atherosclerosis involve observations in patients with multiple sclerosis and psoriasis in small cohorts and for short durations. The findings of these studies need to be assessed in larger prospective clinical trials, ideally with a double-blind randomized study design, investigating the effects on cardiovascular endpoints as well as morbidity and mortality. The long-term impact of DMF therapy on cardiovascular diseases also needs to be confirmed. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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14 pages, 1648 KiB

Open AccessReview

Empagliflozin—A New Chance for Patients with Chronic Heart Failure

by Klaudia Kowalska, Justyna Walczak, Joanna Femlak, Ewelina Młynarska, Beata Franczyk and Jacek Rysz

Pharmaceuticals 2022, 15(1), 47; https://doi.org/10.3390/ph15010047 - 30 Dec 2021

Cited by 5 | Viewed by 3139

Abstract

The heart failure (HF) epidemic is one of the challenges that has been faced by the healthcare system worldwide for almost 25 years. With an ageing world population and a fast-paced lifestyle that promotes the development of cardiovascular disease, the number of people [...] Read more.

The heart failure (HF) epidemic is one of the challenges that has been faced by the healthcare system worldwide for almost 25 years. With an ageing world population and a fast-paced lifestyle that promotes the development of cardiovascular disease, the number of people suffering from heart failure will continue to rise. To improve the treatment regimen and consequently the prognosis and quality of life of heart failure patients, new therapeutic solutions have been introduced, such as an inclusion of Sodium-glucose co-transporter 2 (SGLT-2) inhibitors in a new treatment regimen as announced by the European Society of Cardiology in August 2021. This article focuses on the SGLT2 inhibitor empagliflozin and its use in patients with heart failure. Empagliflozin is a drug originally intended for the treatment of diabetes due to its glycosuric properties, yet its beneficial effects extend beyond lowering glycemia. The pleiotropic effects of the drug include nephroprotection, improving endothelial function, lowering blood pressure and reducing body weight. In this review we discuss the cardioprotective mechanism of the drug in the context of the benefits of empagliflozin use in patients with chronic cardiac insufficiency. Numerous findings confirm that despite its potential limitations, the use of empagliflozin in HF treatment is advantageous and effective. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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18 pages, 849 KiB

Open AccessReview

Treatment of Cardiovascular Disease in Rheumatoid Arthritis: A Complex Challenge with Increased Atherosclerotic Risk

by Saba Ahmed, Benna Jacob, Steven E. Carsons, Joshua De Leon and Allison B. Reiss

Pharmaceuticals 2022, 15(1), 11; https://doi.org/10.3390/ph15010011 - 22 Dec 2021

Cited by 12 | Viewed by 4478

Abstract

Rheumatoid arthritis (RA) carries significant risk for atherosclerotic cardiovascular disease (ASCVD). Traditional ASCVD risk factors fail to account for this accelerated atherosclerosis. Shared inflammatory pathways are fundamental in the pathogenesis of both diseases. Considering the impact of RA in increasing cardiovascular morbidity and [...] Read more.

Rheumatoid arthritis (RA) carries significant risk for atherosclerotic cardiovascular disease (ASCVD). Traditional ASCVD risk factors fail to account for this accelerated atherosclerosis. Shared inflammatory pathways are fundamental in the pathogenesis of both diseases. Considering the impact of RA in increasing cardiovascular morbidity and mortality, the characterization of therapies encompassing both RA and ASCVD management merit high priority. Despite little progress, several drugs discussed here promote remission and or lower rheumatoid disease activity while simultaneously conferring some level of atheroprotection. Methotrexate, a widely used disease-modifying drug used in RA, is associated with significant reduction in cardiovascular adverse events. MTX promotes cholesterol efflux from macrophages, upregulates free radical scavenging and improves endothelial function. Likewise, the sulfonamide drug sulfasalazine positively impacts the lipid profile by increasing HDL-C, and its use in RA has been correlated with reduced risk of myocardial infraction. In the biologic class, inhibitors of TNF-α and IL-6 contribute to improvements in endothelial function and promote anti-atherogenic properties of HDL-C, respectively. The immunosuppressant hydroxychloroquine positively affects insulin sensitization and the lipid profile. While no individual therapy has elicited optimal atheroprotection, further investigation of combination therapies are ongoing. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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Open AccessSystematic Review

Cardioprotective Agents for the Primary Prevention of Trastuzumab-Associated Cardiotoxicity: A Systematic Review and Meta-Analysis

by Kyriakos Goulas, Dimitrios Farmakis, Anastasia Constantinidou and Nikolaos P. E. Kadoglou

Pharmaceuticals 2023, 16(7), 983; https://doi.org/10.3390/ph16070983 - 09 Jul 2023

Cited by 1 | Viewed by 1273

Abstract

There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation. Recently, randomized controlled trials (RCTs) have evaluated the effects of early commitment of beta-blockers (BBs), angiotensin receptor blockers (ARBs) and angiotensin converting [...] Read more.

There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation. Recently, randomized controlled trials (RCTs) have evaluated the effects of early commitment of beta-blockers (BBs), angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) during trastuzumab chemotherapy in order to prevent the related cardiotoxicity. The present systematic review and meta-analysis of six RCTs included patients who have predominantly non-metastatic, HER2-positive, breast cancer and received trastuzumab as primary or adjuvant therapy. Those patients did not have any obvious cardiac dysfunction or any previous therapy with cardioprotective agent. We evaluated the efficacy of the aforementioned medications for primary prevention of cardiotoxicity, using random effects models. Any preventive treatment did not reduce cardiotoxicity occurrence compared to controls (Odds ratios (OR) = 0.92, 95% CI 0.54–1.56, p = 0.75). Results were similar for ACEIs/ARBs and beta-blockers. Treatment with ACEIs/ARBs led to a slight, but significant, increase in LVEF in patients compared to the placebo group. Only two studies reported less likelihood of discontinuation of trastuzumab treatment. More adequately powered RCTs are needed to determine the efficacy of routine prophylactic therapy. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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12 pages, 314 KiB

Open AccessBrief Report

Anti-Inflammatory Drug Candidates for Prevention and Treatment of Cardiovascular Diseases

by Quentin Delbaere, Nicolas Chapet, Fabien Huet, Clément Delmas, Nathan Mewton, Fabrice Prunier, Denis Angoulvant and François Roubille

Pharmaceuticals 2023, 16(1), 78; https://doi.org/10.3390/ph16010078 - 04 Jan 2023

Cited by 5 | Viewed by 1695

Abstract

Incidence and mortality rates for cardiovascular disease are declining, but it still remains a major cause of morbidity and mortality. Drug treatments to slow the progression of atherosclerosis focus on reducing cholesterol levels. The paradigm shift to consider atherosclerosis an inflammatory disease by [...] Read more.

Incidence and mortality rates for cardiovascular disease are declining, but it still remains a major cause of morbidity and mortality. Drug treatments to slow the progression of atherosclerosis focus on reducing cholesterol levels. The paradigm shift to consider atherosclerosis an inflammatory disease by itself has led to the development of new treatments. In this article, we discuss the pathophysiology of inflammation and focus attention on therapeutics targeting different inflammatory pathways of atherosclerosis and myocardial infarction. In atherosclerosis, colchicine is included in new recommendations, and eight randomized clinical trials are testing new drugs in different inflammatory pathways. After a myocardial infarction, no drug has shown a significant benefit, but we present four randomized clinical trials with new treatments targeting inflammation. Full article

(This article belongs to the Special Issue Drug Candidates for the Prevention and Treatment of Cardiovascular Diseases)

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