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Biomedicines
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Advanced and Innovative Therapies of Dyslipidemia
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Advanced and Innovative Therapies of Dyslipidemia

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

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 19090

Special Issue Editor

Prof. Dr. Matteo Di Minno

E-Mail Website
Guest Editor
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Interests: atherosclerosis; dyslipidemia; thrombosis; vascular medicine; hemostasis; thrombophilia; hemophilia; bleeding disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dyslipidemia is a widely recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), and is a leading cause of morbidity and mortality. Although lipid-lowering treatments have been able to decrease the risk for ASCVD, the target LDL-C is not always achieved, mainly in patients with very high levels of LDL-C. In the last years, PCSK9 inhibitors (PCSK9i) have been more and more extensively implemented in clinical practice, providing great efficacy for decreasing LDL-C. However, PCSK9i are expensive, they are administered subcutaneously every 14 days and their long-lasting side effects are not known. Thus, there are continuous attempts to develop further novel, effective, and safe lipid-lowering treatments (bempedoic acid, selective PPAR alpha receptor modulators, etc.), including advanced therapies based on specific antisense oligonucleotide sequences targeting apolipoprotein CIII, lipoprotein (a), apolipoprotein B, or RNA silencing technique (PCSK9 mRNA).

The aim of this Special Issue is to provide an update on the molecular mechanisms, as well as clinical and translational data on novel lipid-lowering treatments, including both reviews and experimental studies.

Prof. Dr. Matteo Di Minno
Guest Editor

Manuscript Submission Information

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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

  • dyslipidemia
  • lipid-lowering treatments
  • atherosclerosis
  • cardiovascular disease

Published Papers (5 papers)

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Research

Jump to: Review

11 pages, 1264 KiB  
Article
Effects of Lipid Lowering Therapy Optimization by PCSK9 Inhibitors on Circulating CD34+ Cells and Pulse Wave Velocity in Familial Hypercholesterolemia Subjects without Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid Units
by Roberto Scicali, Giuseppe Mandraffino, Michele Scuruchi, Alberto Lo Gullo, Antonino Di Pino, Viviana Ferrara, Carmela Morace, Caterina Oriana Aragona, Giovanni Squadrito, Francesco Purrello and Salvatore Piro
Biomedicines 2022, 10(7), 1715; https://doi.org/10.3390/biomedicines10071715 - 15 Jul 2022
Cited by 3 | Viewed by 1202
Abstract
Background: Circulating CD34+ progenitor cells (CD34+CPCs) are characterized by pronounced tissue regeneration activity. Dyslipidemic subjects seemed to have reduced CD34+CPCs, and statin therapy appeared to restore their levels. We aimed to evaluate the effects of PCSK9 inhibitors (PCSK9-i) on CD34+CPCs and pulse wave [...] Read more.
Background: Circulating CD34+ progenitor cells (CD34+CPCs) are characterized by pronounced tissue regeneration activity. Dyslipidemic subjects seemed to have reduced CD34+CPCs, and statin therapy appeared to restore their levels. We aimed to evaluate the effects of PCSK9 inhibitors (PCSK9-i) on CD34+CPCs and pulse wave velocity (PWV) in a cohort of heterozygous familial hypercholesterolemia (HeFH) subjects. Methods: We determined CD34+ cell count and its change after PCSK9-i in 30 selected HeFH subjects and 30 healthy controls. Lipid profile and PWV were evaluated at baseline (T0), 6 months after intensive lipid lowering strategy (statin plus ezetimibe, T1), and after 6 months of optimized therapy with PCSK9-i (T2); CD34+ cell count was reported at T1 and T2. Results: At T1, the median value of CD34+ cells was not significantly different between HeFH subjects and controls, and the same result was obtained at T2. PWV was significantly reduced at T1 (ΔPWV − 14.8%, p < 0.001 vs. T0) and T2 (ΔPWV − 10.96%, p < 0.001 vs. T1). Dividing HeFH subjects into two groups of high- and low-CD34+ cell count, CD34+CPCs appeared to be polarized with a significant difference between the two groups (1.2 (0.46) vs. 4.74 (1.92), p < 0.001), also with respect to controls (both p < 0.001). This polarization was no longer observed at T2, and neither with respect to controls. ΔCD34+ was +67.4% in the low-CD34+ group and −39.24% in the high-CD34+ group (p < 0.001). Lastly, we found a significant correlation between ΔCD34+ cell number and ΔPWV in HeFH subjects (rho = −0.365, p < 0.05), particularly in the low-CD34+ group (rho = −0.681, p < 0.001). Conclusion: PCSK9-i exhibited favorable effects on CD34 + CPCs as was on PWV values in a cohort of FH subjects. Our preliminary findings suggest a possible positive role of this novel lipid-lowering strategy on vascular homeostasis. Full article
(This article belongs to the Special Issue Advanced and Innovative Therapies of Dyslipidemia)
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16 pages, 1249 KiB  
Article
Treatment with PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia Lowers Plasma Levels of Platelet-Activating Factor and Its Precursors: A Combined Metabolomic and Lipidomic Approach
by Alessandro Di Minno, Roberta Clara Orsini, Mattia Chiesa, Viviana Cavalca, Ilenia Calcaterra, Maria Tripaldella, Andrea Anesi, Susanna Fiorelli, Sonia Eligini, Gualtiero I. Colombo, Elena Tremoli, Benedetta Porro and Matteo Nicola Dario Di Minno
Biomedicines 2021, 9(8), 1073; https://doi.org/10.3390/biomedicines9081073 - 23 Aug 2021
Cited by 8 | Viewed by 2516
Abstract
Introduction: Familial hypercholesterolemia (FH) is characterized by extremely high levels of circulating low-density lipoprotein cholesterol (LDL-C) and is caused by mutations of genes involved in LDL-C metabolism, including LDL receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Accordingly, PCSK9 [...] Read more.
Introduction: Familial hypercholesterolemia (FH) is characterized by extremely high levels of circulating low-density lipoprotein cholesterol (LDL-C) and is caused by mutations of genes involved in LDL-C metabolism, including LDL receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/Kexin type 9 (PCSK9). Accordingly, PCSK9 inhibitors (PCSK9i) are effective in LDL-C reduction. However, no data are available on the pleiotropic effect of PCSK9i. To this end, we performed an untargeted metabolomics approach to gather a global view on changes in metabolic pathways in patients receiving treatment with PCSK9i. Methods: Twenty-five FH patients starting treatment with PCSK-9i were evaluated by an untargeted metabolomics approach at baseline (before PCSK9i treatment) and after 12 weeks of treatment. Results: All the 25 FH subjects enrolled were on maximal tolerated lipid-lowering therapy prior to study entry. After a 12 week treatment with PCSK9i, we observed an expected significant reduction in LDL-cholesterol levels (from 201.0 ± 69.5 mg/dL to 103.0 ± 58.0 mg/dL, p < 0.001). The LDL-C target was achieved in 36% of patients. After peak validation and correction, after 12 weeks of PCSK9i treatment as compared to baseline, we observed increments in creatine (p-value = 0.041), indole (p-value = 0.045), and indoleacrylic acid (p-value= 0.045) concentrations. Conversely, significant decreases in choline (p-value = 0.045) and phosphatidylcholine (p-value < 0.01) together with a reduction in platelet activating factor (p-value = 0.041) were observed. Conclusions: Taking advantage of untargeted metabolomics, we first provided evidence of concomitant reductions in inflammation and platelet activation metabolites in FH patients receiving a 12 week treatment with PCSK9i. Full article
(This article belongs to the Special Issue Advanced and Innovative Therapies of Dyslipidemia)
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Review

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14 pages, 912 KiB  
Review
New Treatment Targets and Innovative Lipid-Lowering Therapies in Very-High-Risk Patients with Cardiovascular Disease
by Achim Leo Burger, Edita Pogran, Marie Muthspiel, Christoph Clemens Kaufmann, Bernhard Jäger and Kurt Huber
Biomedicines 2022, 10(5), 970; https://doi.org/10.3390/biomedicines10050970 - 22 Apr 2022
Cited by 8 | Viewed by 3342
Abstract
The effective and fast reduction of circulating low-density lipoprotein cholesterol (LDL-C) is a cornerstone for secondary prevention of atherosclerotic disease progression. Despite the substantial lipid-lowering effects of the established treatment option with statins and ezetimibe, a significant proportion of very-high-risk patients with cardiovascular [...] Read more.
The effective and fast reduction of circulating low-density lipoprotein cholesterol (LDL-C) is a cornerstone for secondary prevention of atherosclerotic disease progression. Despite the substantial lipid-lowering effects of the established treatment option with statins and ezetimibe, a significant proportion of very-high-risk patients with cardiovascular disease do not reach the recommended treatment goal of <55 mg/dL (<1.4 mmol/L). Novel lipid-lowering agents, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies alirocumab and evolocumab, the small interfering ribonucleotide acid (si-RNA) inclisiran, as well as the recently approved bempedoic acid, now complete the current arsenal of LDL-C lowering agents. These innovative therapies have demonstrated promising results in clinical studies. Besides a strong reduction of LDL-C by use of highly effective agents, there is still discussion as to whether a very rapid achievement of the treatment goal should be a new strategic approach in lipid-lowering therapy. In this review, we summarize evidence for the lipid-modifying properties of these novel agents and their safety profiles, and discuss their potential pleiotropic effects beyond LDL-C reduction (if any) as well as their effects on clinical endpoints as cardiovascular mortality. In addition to a treatment strategy of “the lower, the better”, we also discuss the concept of “the earlier, the better”, which may also add to the early clinical benefit of large LDL-C reduction after an acute ischemic event. Full article
(This article belongs to the Special Issue Advanced and Innovative Therapies of Dyslipidemia)
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13 pages, 780 KiB  
Review
Dyslipidemia, Diabetes and Atherosclerosis: Role of Inflammation and ROS-Redox-Sensitive Factors
by Elham Hasheminasabgorji and Jay C. Jha
Biomedicines 2021, 9(11), 1602; https://doi.org/10.3390/biomedicines9111602 - 03 Nov 2021
Cited by 36 | Viewed by 7543
Abstract
The prevalence of diabetes is growing at an alarming rate with increased disability, morbidity, and often premature mortality because of the various complications of this disorder. Chronic hyperglycemia, dyslipidemia, and other metabolic alterations lead to the development and progression of macro- and microvascular [...] Read more.
The prevalence of diabetes is growing at an alarming rate with increased disability, morbidity, and often premature mortality because of the various complications of this disorder. Chronic hyperglycemia, dyslipidemia, and other metabolic alterations lead to the development and progression of macro- and microvascular complications of diabetes including cardiovascular, retinal and kidney disease. Despite advances in glucose and lipid lowering treatments, a large number of diabetic individuals develop one or more types of these complications, ultimately leading to end-organ damage over the time. Atherosclerosis is the major macro-vascular complications of diabetes and the primary underlying cause of cardiovascular disease (CVD) posing heavy burden on the health care system. In this review, we discuss the involvement of dyslipidemia in the progression of atherosclerosis by activating the pro-inflammatory cytokines and oxidative stress-related factors. In addition, we also provide information on various pharmacological agents that provides protection against diabetic atherosclerosis by reducing inflammation and oxidative stress. Full article
(This article belongs to the Special Issue Advanced and Innovative Therapies of Dyslipidemia)
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17 pages, 1079 KiB  
Review
Treatment of Dyslipidaemia in Children
by Riccardo Fiorentino and Francesco Chiarelli
Biomedicines 2021, 9(9), 1078; https://doi.org/10.3390/biomedicines9091078 - 24 Aug 2021
Cited by 15 | Viewed by 3337
Abstract
Childhood dyslipidaemia is one of the main traditional cardiovascular risk factors that initiate and exacerbate the atherosclerotic process. Healthcare providers may play a key role in the management of children with lipid abnormalities; however, they have to properly evaluate the normal lipid values [...] Read more.
Childhood dyslipidaemia is one of the main traditional cardiovascular risk factors that initiate and exacerbate the atherosclerotic process. Healthcare providers may play a key role in the management of children with lipid abnormalities; however, they have to properly evaluate the normal lipid values and know the available treatment options in children and adolescents. Current guidelines recommend healthy behaviours as the first-line treatment for childhood dyslipidaemia. The therapeutic lifestyle changes should focus on dietary modifications, daily physical activity, reduction in body weight and tobacco smoking cessation. Parents play a key role in promoting their children’s healthy habits. In children with more severe forms of lipid abnormalities and in those who do not benefit from healthy behaviours, pharmacological therapy should be considered. Safe and effective medications are already available for children and adolescents. Statins represent the first-line pharmacological option, while ezetimibe and bile acid sequestrants are usually used as second-line drugs. Despite their limited use in children, other lipid-lowering agents (already approved for adults) are currently available or under study for certain categories of paediatric patients (e.g., familial hypercholesterolemia). Further studies are needed to evaluate the long-term efficacy, safety and tolerability of novel lipid-lowering drugs, especially in children. Full article
(This article belongs to the Special Issue Advanced and Innovative Therapies of Dyslipidemia)
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