Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 25976

Special Issue Editors

Dr. Sabata Pierno

E-Mail Website
Guest Editor
Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari "Aldo Moro"-Campus, Via Orabona, 4, 70125 Bari, Italy
Interests: ion channels; chloride channel; skeletal muscle; rare diseases; iatrogenic diseases; statin; ALS; aging; disuse; pharmacology; biophysics; molecular biology
Dr. Olimpia Musumeci

E-Mail Website
Guest Editor
Department of Neuroscience, University of Messina, Messina, Italy

Special Issue Information

Dear Colleagues,

As we all know, statins are the most prescribed and effective lipid-lowering drugs. These drugs are used in different diseases, such as metabolic syndrome, atherosclerosis and cardiovascular disease, that are characterized by altered lipid metabolism and increases in plasma. Although they are highly effective, patients using them therapeutically can experience intolerance and/or statin-associated muscle symptoms, which lead to reduced compliance and discontinuation, with a recrudescence of symptoms. For this, it is important to study several aspects of these drugs at the preclinical and clinical levels, in order to provide evidence of the crucial points. Other synthetic hypolipidemic compounds and new biotechnological drugs, as well as nutraceutical and herbal compounds, can substitute and/or assist statin therapy. Drug-modeling studies and in vitro assays can be of interest for the research of modified compounds able to bind to, with higher affinity, the pharmacological targets.

In this Special Issue, we welcome reviews or experimental papers which demonstrate significant advances in the field of lipid-lowering therapy, risk factors and complementary approaches to manage them. Papers from experts in the field will identify how to better use statin and other substances, and how to make the right choice for personalized therapy. 

Dr. Sabata Pierno
Dr. Olimpia Musumeci
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • pharmacotherapy of lipid-lowering drugs
  • statin intolerance
  • statin-associated muscle symptom
  • causes of myotoxicity and risk factors
  • preclinical and clinical studies
  • identification of new lipid-lowering drugs
  • nutraceuticals for hyperlipidemia
  • personalized therapy

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

5 pages, 693 KiB  
Editorial
Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk
by Sabata Pierno and Olimpia Musumeci
Int. J. Mol. Sci. 2023, 24(2), 996; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24020996 - 04 Jan 2023
Cited by 1 | Viewed by 2158
Abstract
Lipid-lowering drugs are widely used for the prevention and cure of cardiovascular diseases (CVD) [...] Full article
(This article belongs to the Special Issue Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk)
►▼ Show Figures

Figure 1

Research

Jump to: Editorial, Review

17 pages, 3441 KiB  
Article
Impact of Atorvastatin on Skeletal Muscle Mitochondrial Activity, Locomotion and Axonal Excitability—Evidence from ApoE-/- Mice
by Chiara Macchi, Veronica Bonalume, Maria Francesca Greco, Marta Mozzo, Valentina Melfi, Cesare R. Sirtori, Valerio Magnaghi, Alberto Corsini and Massimiliano Ruscica
Int. J. Mol. Sci. 2022, 23(10), 5415; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105415 - 12 May 2022
Cited by 8 | Viewed by 2504
Abstract
The cardiovascular benefit of statins is well established. However, only 20% of high-risk patients remain adequately adherent after 5 years of treatment. Among reasons for discontinuation, statin associated-muscle pain symptoms are the most prevalent. Aim of the present study was to evaluate the [...] Read more.
The cardiovascular benefit of statins is well established. However, only 20% of high-risk patients remain adequately adherent after 5 years of treatment. Among reasons for discontinuation, statin associated-muscle pain symptoms are the most prevalent. Aim of the present study was to evaluate the impact of high dose atorvastatin on skeletal muscle mitochondrial activity, aerobic and anaerobic exercise, and axonal excitability in a murine model of atherosclerosis. ApoE-/- mice were fed 12 weeks a high-fat high-cholesterol diet alone or containing atorvastatin (40 mg/Kg/day). Outcomes were the evaluation of muscle mitochondrial functionality, locomotion, grip test, and axonal excitability (compound action potential recording analysis of Aα motor propioceptive, Aβ mechanoceptive and C nociceptive fibres). Atorvastatin led to a reduction in muscle mitochondrial biogenesis and mitochondrial ATP production. It did not affect muscular strength but led to a time-dependent motor impairment. Atorvastatin altered the responsiveness of mechanoceptive and nociceptive fibres, respectively, the Aβ and C fibres. These findings point out to a mild sensitization on mechanical, tactile and pain sensitivity. In conclusion, although the prevalence of muscular side effects from statins may be overestimated, understanding of the underlying mechanisms can help improve the therapeutic approach and reassure adherence in patients needing-to-be-treated. Full article
(This article belongs to the Special Issue Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk)
►▼ Show Figures

Figure 1

16 pages, 2616 KiB  
Article
Off-Target Effect of Lovastatin Disrupts Dietary Lipid Uptake and Dissemination through Pro-Drug Inhibition of the Mesenteric Lymphatic Smooth Muscle Cell Contractile Apparatus
by Matthew Stephens, Simon Roizes and Pierre-Yves von der Weid
Int. J. Mol. Sci. 2021, 22(21), 11756; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111756 - 29 Oct 2021
Cited by 3 | Viewed by 1752
Abstract
Previously published, off-target effects of statins on skeletal smooth muscle function have linked structural characteristics within this drug class to myopathic effects. However, the effect of these drugs on lymphatic vascular smooth muscle cell function, and by proxy dietary cholesterol uptake, by the [...] Read more.
Previously published, off-target effects of statins on skeletal smooth muscle function have linked structural characteristics within this drug class to myopathic effects. However, the effect of these drugs on lymphatic vascular smooth muscle cell function, and by proxy dietary cholesterol uptake, by the intestinal lymphatic network has not been investigated. Several of the most widely prescribed statins (Atorvastatin, Pravastatin, Lovastatin, and Simvastatin) were tested for their in-situ effects on smooth muscle contractility in rat mesenteric collecting lymphatic vessels. Lovastatin and Simvastatin had a concentration-dependent effect of initially increasing vessel contraction frequency before flatlining the vessel, a phenomenon which was found to be a lactone-ring dependent phenomenon and could be ameliorated through use of Lovastatin- or Simvastatin-hydroxyacid (HA). Simvastatin treatment further resulted in mitochondrial depolymerization within primary-isolated rat lymphatic smooth muscle cells (LMCs) while Lovastatin was found to be acting in a mitochondrial-independent manner, increasing the function of RhoKinase. Lovastatin’s effect on RhoKinase was investigated through pharmacological testing and in vitro analysis of increased MLC and MYPT1 phosphorylation within primary isolated LMCs. Finally, acute in vivo treatment of rats with Lovastatin, but not Lovastatin-HA, resulted in a significantly decreased dietary lipid absorption in vivo through induced disfunction of mesenteric lymph uptake and trafficking. Full article
(This article belongs to the Special Issue Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk)
►▼ Show Figures

Figure 1

16 pages, 3350 KiB  
Article
Effects of Tyrosine and Tryptophan in Rats with Diet-Induced Obesity
by Vladimir A. Shipelin, Nikita V. Trusov, Sergey A. Apryatin, Antonina A. Shumakova, Anastasia S. Balakina, Nikolay A. Riger, Ivan V. Gmoshinski and Dmitry B. Nikityuk
Int. J. Mol. Sci. 2021, 22(5), 2429; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052429 - 28 Feb 2021
Cited by 16 | Viewed by 3488
Abstract
Amino acids tyrosine (Tyr) and tryptophan (Trp) play a significant role in the regulation of energy metabolism, locomotor activity, and eating behavior. We studied the possibility of modulating these processes in obesity by increasing the pool of Tyr and Trp in the experimental [...] Read more.
Amino acids tyrosine (Tyr) and tryptophan (Trp) play a significant role in the regulation of energy metabolism, locomotor activity, and eating behavior. We studied the possibility of modulating these processes in obesity by increasing the pool of Tyr and Trp in the experimental diet. As a model of obesity, we used Wistar rats fed a diet with an excess specific energy value (HFCD) for 64 days. Trp led to a normalization of the rats’ body weight almost to the control level, but increased anxiety-like behavior and decreased long-term memory. The consumption of amino acids resulted in increased grip strength and impairment of short-term memory. The locomotor activity of animals decreased with age as a result of Tyr consumption, while Trp, on the contrary, prevented this. The Tyr supplementation led to the normalization of triglycerides and LDL. In the spleen cell lysates, amino acids suppressed the production of proinflammatory cytokines. The liver tissue morphology showed that the consumption of Tyr noticeably weakened the signs of fatty degeneration. The addition of Trp, on the contrary, led to an unfavorable effect, consisting of the appearance of a high number of large rounded fatty vacuoles. The data obtained indicate a more pronounced anti-inflammatory effect of Tyr as compared to Trp. Full article
(This article belongs to the Special Issue Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research

15 pages, 1718 KiB  
Review
Statins Neuromuscular Adverse Effects
by Silvia Attardo, Olimpia Musumeci, Daniele Velardo and Antonio Toscano
Int. J. Mol. Sci. 2022, 23(15), 8364; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158364 - 28 Jul 2022
Cited by 24 | Viewed by 4510
Abstract
Statins are drugs widely prescribed in high-risk patients for cerebrovascular or cardiovascular diseases and are, usually, safe and well tolerated. However, these drugs sometimes may cause neuromuscular side effects that represent about two-third of all adverse events. Muscle-related adverse events include cramps, myalgia, [...] Read more.
Statins are drugs widely prescribed in high-risk patients for cerebrovascular or cardiovascular diseases and are, usually, safe and well tolerated. However, these drugs sometimes may cause neuromuscular side effects that represent about two-third of all adverse events. Muscle-related adverse events include cramps, myalgia, weakness, immune-mediated necrotizing myopathy and, more rarely, rhabdomyolysis. Moreover, they may lead to peripheral neuropathy and induce or unmask a preexisting neuromuscular junction dysfunction. A clinical follow up of patients assuming statins could reveal early side effects that may cause neuromuscular damage and suggest how to better modulate their use. In fact, statin dechallenge or cessation, or the alternative use of other lipid-lowering agents, can avoid adverse events. This review summarizes the current knowledge on statin-associated neuromuscular adverse effects, diagnosis, and management. It is conceivable that the incidence of neuromuscular complications will increase because, nowadays, use of statins is even more diffused than in the past. On this purpose, it is expected that pharmacogenomic and environmental studies will help to timely predict neuromuscular complications due to statin exposure, leading to a more personalized therapeutic approach. Full article
(This article belongs to the Special Issue Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk)
►▼ Show Figures

Figure 1

11 pages, 599 KiB  
Review
Pleiotropic Effects of PCSK-9 Inhibitors
by Marcin Basiak, Michał Kosowski, Marcin Cyrnek, Łukasz Bułdak, Mateusz Maligłówka, Grzegorz Machnik and Bogusław Okopień
Int. J. Mol. Sci. 2021, 22(6), 3144; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063144 - 19 Mar 2021
Cited by 33 | Viewed by 5621
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) [...] Read more.
Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) from the bloodstream as well as reducing its concentration. The effectiveness of three monoclonal antibodies, namely, alirocumab (human IgG1/κ monoclonal antibody, genetically engineered in Chinese hamster ovary cells), evolocumab (the first fully human monoclonal antibody), and bococizumab (humanized mouse antibody), in inhibiting the action of PCSK-9 and reducing LDLc levels has been confirmed. The first two, after clinical trials, were approved by the Food and Drug Administration (FDA) and are used primarily in the treatment of autosomal familial hypercholesterolemia and in cases of statin intolerance. They are currently used both as monotherapy and in combination with statins and ezetimibe to intensify therapy and achieve therapeutic goals following the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines. However, the lipid-lowering effect is not the only effect of action described by researchers that PCSK-9 inhibitors have. This paper is a review of the literature describing the pleiotropic effects of PCSK-9 inhibitors, which belong to a group of drugs that are being increasingly used, especially when standard lipid-lowering therapy fails. The article focuses on activities other than lipid-lowering, such as the anti-atherosclerotic effect and stabilization of atherosclerotic plaque, the anti-aggregation effect, the anticoagulant effect, the antineoplastic effect, and the ability to influence the course of bacterial infections. In this publication, we try to systematically review the current scientific data, both from our own scientific work and knowledge from international publications. Full article
(This article belongs to the Special Issue Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk)
►▼ Show Figures

Figure 1

19 pages, 820 KiB  
Review
Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence
by Giulia Maria Camerino, Nancy Tarantino, Ileana Canfora, Michela De Bellis, Olimpia Musumeci and Sabata Pierno
Int. J. Mol. Sci. 2021, 22(4), 2070; https://doi.org/10.3390/ijms22042070 - 19 Feb 2021
Cited by 15 | Viewed by 4981
Abstract
Statins are the most prescribed and effective drugs to treat cardiovascular diseases (CVD). Nevertheless, these drugs can be responsible for skeletal muscle toxicity which leads to reduced compliance. The discontinuation of therapy increases the incidence of CVD. Thus, it is essential to assess [...] Read more.
Statins are the most prescribed and effective drugs to treat cardiovascular diseases (CVD). Nevertheless, these drugs can be responsible for skeletal muscle toxicity which leads to reduced compliance. The discontinuation of therapy increases the incidence of CVD. Thus, it is essential to assess the risk. In fact, many studies have been performed at preclinical and clinical level to investigate pathophysiological mechanisms and clinical implications of statin myotoxicity. Consequently, new toxicological aspects and new biomarkers have arisen. Indeed, these drugs may affect gene transcription and ion transport and contribute to muscle function impairment. Identifying a marker of toxicity is important to prevent or to cure statin induced myopathy while assuring the right therapy for hypercholesterolemia and counteracting CVD. In this review we focused on the mechanisms of muscle damage discovered in preclinical and clinical studies and highlighted the pathological situations in which statin therapy should be avoided. In this context, preventive or substitutive therapies should also be evaluated. Full article
(This article belongs to the Special Issue Pharmacotherapy of the Lipid-Lowering Drugs: Update on Efficacy and Risk)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop