PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation
Extensive evidence from epidemiologic, genetic, and clinical intervention studies has indisputably shown that elevated low-density lipoprotein cholesterol (LDL-C) concentrations play a central role in the pathophysiology of atherosclerotic cardiovascular disease. Apart from LDL-C, also triglycerides...
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doaj-1e73690f24204ba3b02b19acd780a9552020-11-25T04:01:37ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-11-011110.3389/fphys.2020.602497602497PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and InflammationIoanna Andreadou0Maria Tsoumani1Gemma Vilahur2Gemma Vilahur3Ignatios Ikonomidis4Lina Badimon5Lina Badimon6Lina Badimon7Zoltán V. Varga8Zoltán V. Varga9Péter Ferdinandy10Péter Ferdinandy11Rainer Schulz12Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, GreeceLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, GreeceCardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, SpainCIBERCV, Instituto Salud Carlos III, Madrid, SpainSecond Cardiology Department, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, GreeceCardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, SpainCIBERCV, Instituto Salud Carlos III, Madrid, SpainCardiovascular Research Chair, Autonomous University of Barcelona (UAB), BarcelonaSpainDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, HungaryHCEMM-SU Cardiometabolic Immunology Research Group, Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, HungaryPharmahungary Group, Szeged, HungaryInstitute for Physiology, Justus-Liebig University Giessen, Giessen, GermanyExtensive evidence from epidemiologic, genetic, and clinical intervention studies has indisputably shown that elevated low-density lipoprotein cholesterol (LDL-C) concentrations play a central role in the pathophysiology of atherosclerotic cardiovascular disease. Apart from LDL-C, also triglycerides independently modulate cardiovascular risk. Reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma LDL-C, but it is also associated with a reduction in triglyceride levels potentially through modulation of the expression of free fatty acid transporters. Preclinical data indicate that PCSK9 is up-regulated in the ischaemic heart and decreasing PCSK9 expression impacts on infarct size, post infarct inflammation and remodeling as well as cardiac dysfunction following ischaemia/reperfusion. Clinical data support that notion in that PCSK9 inhibition is associated with reductions in the incidence of myocardial infarction, stroke, and coronary revascularization and an improvement of endothelial function in subjects with increased cardiovascular risk. The aim of the current review is to summarize the current knowledge on the importance of free fatty acid metabolism on myocardial ischaemia/reperfusion injury and to provide an update on recent evidence on the role of hyperlipidemia and PCSK9 in myocardial infarction and cardioprotection.https://www.frontiersin.org/articles/10.3389/fphys.2020.602497/fulldyslipidemiaheart failureischaemiaLDL cholesterolmyocardial infarctionPCSK9 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ioanna Andreadou Maria Tsoumani Gemma Vilahur Gemma Vilahur Ignatios Ikonomidis Lina Badimon Lina Badimon Lina Badimon Zoltán V. Varga Zoltán V. Varga Péter Ferdinandy Péter Ferdinandy Rainer Schulz |
spellingShingle |
Ioanna Andreadou Maria Tsoumani Gemma Vilahur Gemma Vilahur Ignatios Ikonomidis Lina Badimon Lina Badimon Lina Badimon Zoltán V. Varga Zoltán V. Varga Péter Ferdinandy Péter Ferdinandy Rainer Schulz PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation Frontiers in Physiology dyslipidemia heart failure ischaemia LDL cholesterol myocardial infarction PCSK9 |
author_facet |
Ioanna Andreadou Maria Tsoumani Gemma Vilahur Gemma Vilahur Ignatios Ikonomidis Lina Badimon Lina Badimon Lina Badimon Zoltán V. Varga Zoltán V. Varga Péter Ferdinandy Péter Ferdinandy Rainer Schulz |
author_sort |
Ioanna Andreadou |
title |
PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation |
title_short |
PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation |
title_full |
PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation |
title_fullStr |
PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation |
title_full_unstemmed |
PCSK9 in Myocardial Infarction and Cardioprotection: Importance of Lipid Metabolism and Inflammation |
title_sort |
pcsk9 in myocardial infarction and cardioprotection: importance of lipid metabolism and inflammation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2020-11-01 |
description |
Extensive evidence from epidemiologic, genetic, and clinical intervention studies has indisputably shown that elevated low-density lipoprotein cholesterol (LDL-C) concentrations play a central role in the pathophysiology of atherosclerotic cardiovascular disease. Apart from LDL-C, also triglycerides independently modulate cardiovascular risk. Reduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for reducing plasma LDL-C, but it is also associated with a reduction in triglyceride levels potentially through modulation of the expression of free fatty acid transporters. Preclinical data indicate that PCSK9 is up-regulated in the ischaemic heart and decreasing PCSK9 expression impacts on infarct size, post infarct inflammation and remodeling as well as cardiac dysfunction following ischaemia/reperfusion. Clinical data support that notion in that PCSK9 inhibition is associated with reductions in the incidence of myocardial infarction, stroke, and coronary revascularization and an improvement of endothelial function in subjects with increased cardiovascular risk. The aim of the current review is to summarize the current knowledge on the importance of free fatty acid metabolism on myocardial ischaemia/reperfusion injury and to provide an update on recent evidence on the role of hyperlipidemia and PCSK9 in myocardial infarction and cardioprotection. |
topic |
dyslipidemia heart failure ischaemia LDL cholesterol myocardial infarction PCSK9 |
url |
https://www.frontiersin.org/articles/10.3389/fphys.2020.602497/full |
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