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Biomedicines
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Cardiovascular Medicine: From Bench to Bedside
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Cardiovascular Medicine: From Bench to Bedside

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 16573

Special Issue Editor

Dr. Benedetta Porro

E-Mail Website
Guest Editor
IRCCS Centro Cardiologico Monzino, Milan, Italy
Interests: cardiovascular disease; oxidative stress; endothelial dysfunction, red blood cell; metabolomics; pharmacometabolomics; liquid chromatography-tandem mass spectrometry

Special Issue Information

Dear Colleagues,

Cardiovascular disease (CVD) is a leading cause of deaths worldwide, with deaths due to atherothrombosis expected to increase yearly from 17.3 to 23.6 million by 2030.  In the recent years, constant progresses in medical research, in parallel to the development of new techniques, have allowed better descriptions of the complex network of factors that are involved and cumulatively interact in the onset of the atherosclerotic phenomenon and in its progression. In this field, the improvement of omics approaches is helping to unravel the role of new and already known processes related to CVD development (e.g., oxidative stress, endothelial dysfunction, inflammation, fatty acid oxidation) beyond traditional risk factors. This is crucial for the development of innovative strategies in CVD prevention (including novel laboratory technologies to explore metabolic alterations and molecular studies of predisposition genes) and treatment. To identify appropriate targets in CVD prevention and treatment, the most advanced research information in the area field should be gathered and related or translated to practical (clinical and pathophysiological) questions. This is the aim and purpose of the present Special Issue of the journal.

Dr. Benedetta Porro
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiovascular disease
  • oxidative stress
  • endothelial dysfunction
  • red blood cell
  • circulating biomarker
  • liquid chromatography-tandem mass spectrometry

Published Papers (7 papers)

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Research

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11 pages, 2281 KiB  
Article
Investigation of Platelet Apoptosis in Patients after Surgical Myocardial Revascularization
by Alisa A. Sokolovskaya, Mikhail A. Popov, Ekaterina A. Sergeeva, Arkadiy A. Metelkin, Dmitry I. Zybin, Dmitry V. Shumakov and Aslan A. Kubatiev
Biomedicines 2023, 11(2), 251; https://doi.org/10.3390/biomedicines11020251 - 18 Jan 2023
Viewed by 1338
Abstract
Platelets are one of the main participants in vascular accidents in cases of coronary heart disease (CHD). In this study, we sought to detect platelet apoptosis in patients with coronary artery disease who underwent scheduled myocardial revascularization surgery. To identify apoptotic events, we [...] Read more.
Platelets are one of the main participants in vascular accidents in cases of coronary heart disease (CHD). In this study, we sought to detect platelet apoptosis in patients with coronary artery disease who underwent scheduled myocardial revascularization surgery. To identify apoptotic events, we analyzed phosphatidylserine (PS) expression on the surface of platelets and mitochondrial membrane potential (ΔΨm) by flow cytometry in two groups of 30 patients aged 45–60 years: Group 1—patients before myocardial revascularization surgery and group 2—patients after myocardial revascularization surgery. The control group consisted of 10 healthy volunteers aged 45–60 years. According to our data, the percentage levels of PS expression in patients greatly decreased after surgery. We confirmed platelet apoptosis by recording depolarization of ΔΨm in pre- and postoperative patients. ΔΨm readings were considerably improved after surgery. Our data indicated that the functional parameters of platelets in patients with coronary heart disease differed from the characteristics of platelets in patients who underwent myocardial revascularization, and from those of patients in a control group. Future studies of platelet phenotypic characteristics and platelet apoptosis biomarkers should greatly advance our understanding of the pathophysiology of coronary heart disease, and further promote the development of methods for predicting adverse outcomes after surgery. Full article
(This article belongs to the Special Issue Cardiovascular Medicine: From Bench to Bedside)
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14 pages, 1826 KiB  
Article
Heterogeneous Maturation of Arterio-Venous Fistulas and Loop-Shaped Venous Interposition Grafts: A Histological and 3D Flow Simulation Comparison
by Balazs Szabo, Balazs Gasz, Laszlo Adam Fazekas, Adam Varga, Levente Kiss-Papai, Orsolya Matolay, Zsofia Rezsabek, Mohammad W. Al-Smadi and Norbert Nemeth
Biomedicines 2022, 10(7), 1508; https://doi.org/10.3390/biomedicines10071508 - 25 Jun 2022
Cited by 3 | Viewed by 1861
Abstract
Vascular graft maturation is associated with blood flow characteristics, such as velocity, pressure, vorticity, and wall shear stress (WSS). Many studies examined these factors separately. We aimed to examine the remodeling of arterio-venous fistulas (AVFs) and loop-shaped venous interposition grafts, together with 3D [...] Read more.
Vascular graft maturation is associated with blood flow characteristics, such as velocity, pressure, vorticity, and wall shear stress (WSS). Many studies examined these factors separately. We aimed to examine the remodeling of arterio-venous fistulas (AVFs) and loop-shaped venous interposition grafts, together with 3D flow simulation. Thirty male Wistar rats were randomly and equally divided into sham-operated, AVF, and loop-shaped venous graft (Loop) groups, using the femoral and superficial inferior epigastric vessels for anastomoses. Five weeks after surgery, the vessels were removed for histological evaluation, or plastic castings were made and scanned for 3D flow simulation. Remodeling of AVF and looped grafts was complete in 5 weeks. Histology showed heterogeneous morphology depending on the distribution of intraluminal pressure and WSS. In the Loop group, an asymmetrical WSS distribution coincided with the intima hyperplasia spots. The tunica media was enlarged only when both pressure and WSS were high. The 3D flow simulation correlated with the histological findings, identifying “hotspots” for intimal hyperplasia formation, suggesting a predictive value. These observations can be useful for microvascular research and for quality control in microsurgical training. Full article
(This article belongs to the Special Issue Cardiovascular Medicine: From Bench to Bedside)
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13 pages, 1821 KiB  
Article
Oxidative Stress and Arginine/Nitric Oxide Pathway in Red Blood Cells Derived from Patients with Prediabetes
by Sonia Eligini, Benedetta Porro, José Pablo Werba, Nicolò Capra, Stefano Genovese, Arianna Greco, Viviana Cavalca and Cristina Banfi
Biomedicines 2022, 10(6), 1407; https://doi.org/10.3390/biomedicines10061407 - 14 Jun 2022
Cited by 3 | Viewed by 1717
Abstract
The effects of the oral glucose tolerance test (OGTT) on red blood cells (RBCs) have not been thoroughly investigated, although it is known that the ingestion of 75 g of glucose during OGTT results in a systemic state of inflammation and oxidative stress. [...] Read more.
The effects of the oral glucose tolerance test (OGTT) on red blood cells (RBCs) have not been thoroughly investigated, although it is known that the ingestion of 75 g of glucose during OGTT results in a systemic state of inflammation and oxidative stress. Therefore, we evaluated the effect of OGTT on oxidative stress and L-arginine/Nitric Oxide (L-Arg/NO) metabolic pathway in RBCs obtained from patients with prediabetes. Blood samples were collected from all participants before (T0) and at 10 (T1), 20 (T2), 30 (T3), 60 (T4), 90 (T5), 120 (T6), 150 (T7), and 180 (T8) minutes after glucose loading. Results showed a significant increase in oxidative stress status characterized by a rise in the GSSG/GSH ratio at T4 and T6 that increased in parallel with a reduction of NO production in RBCs. In addition, in this time frame, increased exposure of phosphatidylserine on RBCs membrane was observed. These metabolic modifications were rescued at T8, together with an increase in activated RBC NO synthase expression. These findings provide a possible explanation of the phenomena occurring after glucose loading and suggest that, even in the early stages of diabetes, it may be important to avoid acute variations in glycemia in order to prevent diabetic complications. Full article
(This article belongs to the Special Issue Cardiovascular Medicine: From Bench to Bedside)
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20 pages, 3946 KiB  
Article
Artificial-Intelligence-Assisted Discovery of Genetic Factors for Precision Medicine of Antiplatelet Therapy in Diabetic Peripheral Artery Disease
by Chi-Hsiao Yeh, Yi-Ju Chou, Tsung-Hsien Tsai, Paul Wei-Che Hsu, Chun-Hsien Li, Yun-Hsuan Chan, Shih-Feng Tsai, Soh-Ching Ng, Kuei-Mei Chou, Yu-Ching Lin, Yu-Hsiang Juan, Tieh-Cheng Fu, Chi-Chun Lai, Huey-Kang Sytwu and Ting-Fen Tsai
Biomedicines 2022, 10(1), 116; https://doi.org/10.3390/biomedicines10010116 - 6 Jan 2022
Cited by 6 | Viewed by 2842
Abstract
An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we [...] Read more.
An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients. Full article
(This article belongs to the Special Issue Cardiovascular Medicine: From Bench to Bedside)
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13 pages, 1060 KiB  
Article
GJA1 Expression and Left Atrial Remodeling in the Incidence of Atrial Fibrillation in Patients with Obstructive Sleep Apnea Syndrome
by Yung-Lung Chen, Yung-Che Chen, Ya-Ting Chang, Hui-Ting Wang, Wen-Hao Liu, Shaur-Zheng Chong, Pei-Ting Lin, Po-Yuan Hsu, Mao-Chang Su and Meng-Chih Lin
Biomedicines 2021, 9(10), 1463; https://doi.org/10.3390/biomedicines9101463 - 13 Oct 2021
Cited by 7 | Viewed by 1899
Abstract
Obstructive sleep apnea syndrome (OSAS) is an important risk factor for atrial fibrillation (AF). GJA1 gene encoding connexin43, a major protein in cardiac gap junctions, plays a crucial role in the synchronized contraction of the heart and in cardiac arrhythmia. However, little is [...] Read more.
Obstructive sleep apnea syndrome (OSAS) is an important risk factor for atrial fibrillation (AF). GJA1 gene encoding connexin43, a major protein in cardiac gap junctions, plays a crucial role in the synchronized contraction of the heart and in cardiac arrhythmia. However, little is known regarding the role of GJA1 expression in the incidence of AF in patients with OSAS. All prospectively enrolled OSAS patients underwent polysomnography, electrocardiography, a 24-h Holter test, and echocardiography. Moderate-to-severe OSAS was defined as an apnea-hypopnea index (AHI) ≥ 15. Exosomes were purified from the plasma of all OSAS patients and incubated in HL-1 cells to investigate the effect of exosomes from patients with and without AF on GJA1 expression. A total of 129 patients were recruited for this study; 26 were excluded due to an AHI < 15. Of the 103 enrolled patients, 21 had AF, and 82 did not. Multivariate analysis showed diabetes mellitus, lower sleep efficiency, lower left ventricular ejection fraction, and larger left atrial (LA) size were independent predictors of AF occurrence in OSAS patients. The area under the receiver operating characteristic curve for LA with a size ≥38.5 mm for predicting AF occurrence in OSAS patients was 0.795 (95% confidence interval [0.666, 0.925]); p < 0.001). GJA1 expression in HL-1 cells incubated with exosomes from OSAS patients with AF was lower than that with exosomes from patients without AF after controlling for age and sex and was negatively correlated with the AHI and oxygen desaturation index (ODI), especially during the non-rapid eye movement period (NREM) of OSAS patients with AF (all p < 0.05). LA size was an independent predictor of AF occurrence in OSAS patients. The AHI and ODI in the NREM period of OSAS patients with AF were negatively correlated with GJA1 expression in HL-1 cells, which offers a hint that GJA1 may play a crucial role in the development of AF in patients with OSAS. Full article
(This article belongs to the Special Issue Cardiovascular Medicine: From Bench to Bedside)
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25 pages, 15431 KiB  
Article
Long Term Response to Circulating Angiogenic Cells, Unstimulated or Atherosclerotic Pre-Conditioned, in Critical Limb Ischemic Mice
by Lucía Beltrán-Camacho, Margarita Jiménez-Palomares, Ismael Sanchez-Gomar, Antonio Rosal-Vela, Marta Rojas-Torres, Sara Eslava-Alcon, Jose Angel Alonso-Piñero, Almudena González-Rovira, Mª Jesús Extremera-García, Rosario Conejero, Esther Doiz, Manuel Rodriguez-Piñero, Martin R. Larsen and Mª Carmen Duran-Ruiz
Biomedicines 2021, 9(9), 1147; https://doi.org/10.3390/biomedicines9091147 - 3 Sep 2021
Cited by 3 | Viewed by 2704
Abstract
Critical limb ischemia (CLI), the most severe form of peripheral artery disease, results from the blockade of peripheral vessels, usually correlated to atherosclerosis. Currently, endovascular and surgical revascularization strategies cannot be applied to all patients due to related comorbidities, and even so, most [...] Read more.
Critical limb ischemia (CLI), the most severe form of peripheral artery disease, results from the blockade of peripheral vessels, usually correlated to atherosclerosis. Currently, endovascular and surgical revascularization strategies cannot be applied to all patients due to related comorbidities, and even so, most patients require re-intervention or amputation within a year. Circulating angiogenic cells (CACs) constitute a good alternative as CLI cell therapy due to their vascular regenerative potential, although the mechanisms of action of these cells, as well as their response to pathological conditions, remain unclear. Previously, we have shown that CACs enhance angiogenesis/arteriogenesis from the first days of administration in CLI mice. Also, the incubation ex vivo of these cells with factors secreted by atherosclerotic plaques promotes their activation and mobilization. Herein, we have evaluated the long-term effect of CACs administration in CLI mice, whether pre-stimulated or not with atherosclerotic factors. Remarkably, mice receiving CACs and moreover, pre-stimulated CACs, presented the highest blood flow recovery, lower progression of ischemic symptoms, and decrease of immune cells recruitment. In addition, many proteins potentially involved, like CD44 or matrix metalloproteinase 9 (MMP9), up-regulated in response to ischemia and decreased after CACs administration, were identified by a quantitative proteomics approach. Overall, our data suggest that pre-stimulation of CACs with atherosclerotic factors might potentiate the regenerative properties of these cells in vivo. Full article
(This article belongs to the Special Issue Cardiovascular Medicine: From Bench to Bedside)
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Review

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14 pages, 976 KiB  
Review
Catestatin as a Biomarker of Cardiovascular Diseases: A Clinical Perspective
by Josko Bozic, Marko Kumric, Tina Ticinovic Kurir, Hrvoje Urlic, Dinko Martinovic, Marino Vilovic, Nada Tomasovic Mrcela and Josip A. Borovac
Biomedicines 2021, 9(12), 1757; https://doi.org/10.3390/biomedicines9121757 - 25 Nov 2021
Cited by 19 | Viewed by 2882
Abstract
Accounting for almost one-third of the global mortality, cardiovascular diseases (CVDs) represent a major global health issue. Emerging data suggest that most of the well-established mechanistic explanations regarding the cardiovascular pathophysiology are flawed, and cannot fully explain the progression and long-term effects of [...] Read more.
Accounting for almost one-third of the global mortality, cardiovascular diseases (CVDs) represent a major global health issue. Emerging data suggest that most of the well-established mechanistic explanations regarding the cardiovascular pathophysiology are flawed, and cannot fully explain the progression and long-term effects of these diseases. On the other hand, dysregulation of the sympathetic nervous system (SNS) has emerged as an important player in the pathophysiology of CVDs. Even though upregulated SNS activity is an essential compensatory response to various stress conditions, in the long term, it becomes a major contributor to both cardiac dysfunction and vascular damage. Despite the fact that the importance of SNS hyperactivity in the setting of CVDs has been well-appreciated, its exact quantification and clinical application in either diagnostics or therapy of CVDs is still out of reach. Nevertheless, in recent years a number of novel laboratory biomarkers implicated in the pathophysiology of SNS activation have been explored. Specifically, in this review, we aimed to discuss the role of catestatin, a potent physiological inhibitor of catecholamine spillover that offers cardioprotective effects. Limited data indicate that catestatin could also be a reliable indirect marker of SNS activity and it is likely that high CST levels reflect advanced CV disease burden. Consequently, large-scale studies are required to validate these observations in the upcoming future. Full article
(This article belongs to the Special Issue Cardiovascular Medicine: From Bench to Bedside)
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