scholarly journals Statins: unexpected help in COVID-19

2020 ◽  
Vol 26 (5) ◽  
pp. 509-517
Author(s):  
D. F. Gareeva ◽  
T. I. Musin ◽  
V. N. Pavlov ◽  
P. A. Davtyan ◽  
V. Sh. Ishmetov ◽  
...  
Keyword(s):  
Observational Studies ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Viral Myocarditis ◽  
Cardiovascular Complications ◽  
Lipid Concentration ◽  
Angiotensin Converting Enzyme 2 ◽  
Reductase Inhibitors ◽  
Huge Impact ◽  
Coa Reductase

The COVID-19 pandemic has had a huge impact on the health of millions of people around the world on an unprecedented scale. Unfortunately, the process of creating effective antiviral drugs and vaccines is being delayed. Therefore, drugs that are already available and may have an effect on COVID-19 are being investigated. Due to the fact that viral infection often affects the cardiovascular system, causing myocardial infarction, viral myocarditis, tachyarrhythmias and stress cardiomyopathies, a theory was put forward that HMG-CoA reductase (3-hydroxy-3methyl-glutaryl-CoA reductase) inhibitors (statins) can reduce the risk of cardiovascular complications in these patients. In recent years, this class of drugs has been proposed, including for viral infections, such as the influenza virus or MERS-CoV. The review discusses both the latest clinical data on the efficacy of statins in COVID-19 and the pleotropic mechanisms of statins that can limit the pathogenic effect of viruses. In particular, statins can act on lipid cell rafts (subdomains of the plasma membrane), decreasing their lipid concentration; limiting the interaction of the virus with the receptors of angiotensin-converting enzyme-2 and CD-147. Statins have an antiinflammatory effect (blocking the molecular mechanisms of inflammation, including NF-κB and NLRP3), limit the development of a “cytokine storm” in severe patients with COVID-19; can inhibit SARS-CoV-2 basic protease; influence coagulation, limit sympathetic activity and have other effects. In two large cohort observational studies (n = 96032 and n = 13981), hospitalized patients with COVID-19 who were taking statins showed a decrease in hospital mortality and mortality 28 days after the admission to the hospital. Thus, statins can play a role in the treatment of COVID-19.

scholarly journals The regulation of ACE-2 in the heart and lungs

2021 ◽  
Vol 9 (40) ◽  
pp. 47-52
Author(s):  
Jonathan Kopel ◽  
Thomas Tenner ◽  
Gregory Brower
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Physiological Responses ◽  
Cardiovascular Complications ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Metabolism Regulation

The pathogenesis of SARS-CoV-2 infection or COVID-19 disease remains an active and rapidly evolving area of investigation. Currently, the angiotensin-converting enzyme 2 protein (ACE-2) is the primary receptor implicated in the pathogenesis of SARS-CoV-2. In normal physiological responses, the ACE-2 has important roles in regulating the renin-angiotensin systems (RAS) in several organs, including the heart, kidney, and lungs. Dysregulation of ACE-2 has been linked to heart failure, pulmonary hypertension, and diabetic cardiovascular complications. Two main risk factors for COVID-19 include hypertension and cardiovascular disease. However, the precise mechanism causing these risk factors for COVID-19 infectivity remains unknown. In this paper, we provide possible molecular mechanisms that underlie the cardiovascular risk factors for COVID-19. Keywords: SARS-CoV-2, COVID-19, angiotensin converting enzyme-2 (ACE-2), hormones, cardiovascular, hypoxia, metabolism, regulation, and pathophysiology

HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced “inside-out” signaling to extracellular matrix by preventing RhoA activation

2006 ◽  
Vol 291 (5) ◽  
pp. F995-F1004 ◽  
Author(s):  
Hanshi Xu ◽  
Lixia Zeng ◽  
Hui Peng ◽  
Sheldon Chen ◽  
Jonathan Jones ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Mevalonate Pathway ◽  
Cell Permeability ◽  
Hmg Coa Reductase ◽  
Rhoa Activation ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors exert modulatory effects on a number of cell signaling cascades by preventing the synthesis of various isoprenoids derived from the mevalonate pathway. In the present study, we describe a novel pleiotropic effect of HMG-CoA reductase inhibitors, also commonly known as statins, on vascular endothelial growth factor (VEGF)-induced type IV collagen accumulation. VEGF is an angiogenic polypeptide that is also known to play a central role in endothelial cell permeability and differentiation. Recently, VEGF has also been implicated in promoting extracellular matrix (ECM) accumulation, although the precise signaling mechanism that mediates VEGF-induced ECM expansion remains poorly characterized. Elucidation of the mechanisms through which VEGF exerts its effect on ECM is clearly a prerequisite for both understanding the complex biology of this molecule as well as targeting VEGF in several pathological processes. To this end, this study explored the underlying molecular mechanisms mediating VEGF-induced ECM expansion in mesangial cells. Our findings show that VEGF stimulation elicits a robust increase in ECM accumulation that involves RhoA activation, an intact actin cytoskeleton, and β1- integrin activation. Our data also indicate that simvastatin, via mevalonate depletion, reverses VEGF-induced ECM accumulation by preventing RhoA activation.

scholarly journals The PCSK9 revolution and the potential of PCSK9-based therapies to reduce LDL-cholesterol

2017 ◽  
Vol 2017 (1) ◽  
Author(s):  
Nabil G Seidah
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Cardiovascular Death ◽  
Cardiovascular Complications ◽  
Inherited Disease ◽  
Reductase Inhibitors ◽  
Target Values ◽  
Niemann Pick ◽  
Coa Reductase

[first paragraph of article]A large number of clinical trials over the last 30 years have firmly consolidated the importance of lowering low density lipoprotein cholesterol (LDLc) in the prevention of cardiovascular diseases (CVD) and its associated devastating sequelae. While healthy diets and exercise are highly recommended to lower LDLc levels, in many individuals with high baseline levels of LDLc, this is not sufficient to bring levels down to recommended target values in order to prevent recurrent coronary heart disease and cardiovascular complications. This is especially true for patients at high risk of premature cardiovascular death and disability, including those with familial hypercholesterolaemia (FH). FH is a very common inherited disease – affecting at least 30 million people worldwide, with an overall incidence of 1:200 globally – of whom ≤ 1% have been diagnosed. The advent of HMG-CoA reductase inhibitors, also known as ‘‘statins’’, and their first application to hypercholesterolemic patients over 30 years ago, has revolutionized the treatment of FH patients and resulted in substantial lowering of LDLc. In addition, cholesterol– lowering drugs, such as ‘‘ezetimibe’’ that blocks cholesterol absorption from the gut by inhibiting the Niemann-Pick C1-like 1 (NPC1L1) transporter, have also been successful and a 7-year IMPROVE-IT trial revealed that a ‘‘simvastatin-ezetimibe’’ combination resulted in an incremental lowering of LDLc levels and a modest 2% improved cardiovascular outcomes.3 Therefore, it became clear that additional treatments are needed to substantially decrease LDLc and efficiently protect against CVD. 

scholarly journals Viral Myocarditis—From Pathophysiology to Treatment

2021 ◽  
Vol 10 (22) ◽  
pp. 5240
Author(s):  
Heinz-Peter Schultheiss ◽  
Christian Baumeier ◽  
Ganna Aleshcheva ◽  
C.-Thomas Bock ◽  
Felicitas Escher
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Treatment Options ◽  
Viral Myocarditis ◽  
Severe Heart Failure ◽  
Diagnostic Methods ◽  
Diagnostic Tools ◽  
Public Health Issue ◽  
Chronic Myocarditis ◽  
Significant Public Health

The diagnosis of acute and chronic myocarditis remains a challenge for clinicians. Characterization of this disease has been hampered by its diverse etiologies and heterogeneous clinical presentations. Most cases of myocarditis are caused by infectious agents. Despite successful research in the last few years, the pathophysiology of viral myocarditis and its sequelae leading to severe heart failure with a poor prognosis is not fully understood and represents a significant public health issue globally. Most likely, at a certain point, besides viral persistence, several etiological types merge into a common pathogenic autoimmune process leading to chronic inflammation and tissue remodeling, ultimately resulting in the clinical phenotype of dilated cardiomyopathy. Understanding the underlying molecular mechanisms is necessary to assess the prognosis of patients and is fundamental to appropriate specific and personalized therapeutic strategies. To reach this clinical prerequisite, there is the need for advanced diagnostic tools, including an endomyocardial biopsy and guidelines to optimize the management of this disease. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has currently led to the worst pandemic in a century and has awakened a special sensitivity throughout the world to viral infections. This work aims to summarize the pathophysiology of viral myocarditis, advanced diagnostic methods and the current state of treatment options.

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

Statins and Inflammation in Cardiovascular Disease

2018 ◽  
Vol 23 (46) ◽  
pp. 7027-7039 ◽  
Author(s):  
Georgia Vogiatzi ◽  
Evangelos Oikonomou ◽  
Gerasimos Siasos ◽  
Sotiris Tsalamandris ◽  
Alexandros Briasoulis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Ample Evidence ◽  
Reductase Inhibitors ◽  
Immune System Activation ◽  
Hmg Coa Reductase Inhibitors ◽  
Anti Inflammatory ◽  
Artery Disease ◽  
Coa Reductase

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. </P><P> Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. </P><P> Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. </P><P> Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. </P><P> Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

Sign in / Sign up

Export Citation Format

Share Document