Angelos D Karagiannis1, Martin Liu1, Peter P Toth2, Shijia Zhao1, Devendra K Agrawal3, Peter Libby4, Yiannis S Chatzizisis5. 1. Cardiovascular Biology and Biomechanics Laboratory, Cardiovascular Division, University of Nebraska Medical Center, 982265 Nebraska Medical Center, Omaha, NE, 68198, USA. 2. CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, USA. 4. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 5. Cardiovascular Biology and Biomechanics Laboratory, Cardiovascular Division, University of Nebraska Medical Center, 982265 Nebraska Medical Center, Omaha, NE, 68198, USA. ychatzizisis@icloud.com.
Abstract
PURPOSE OF REVIEW: Clinical trials with PCSK9 inhibitors have shown a robust decrease in plasma LDL levels and a significant reduction in the incidence of cardiovascular atherosclerotic events. However, the role of PCSK9 in atherosclerosis is not well investigated and it remains unclear whether PCSK9 inhibition has direct, LDL-independent, anti-atherosclerotic effects. This review outlines the molecular pathways and targets of PCSK9 in atherosclerosis and summarizes the experimental and clinical data supporting the anti-atherosclerotic (pleiotropic) actions of PCSK9 inhibitors. RECENT FINDINGS: PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g., endothelial cell, smooth muscle cell, and macrophage) and is detected inside human atherosclerotic plaque. Preclinical studies have shown that inhibition of PCSK9 can attenuate atherogenesis and plaque inflammation. Besides increasing plasma LDL, PCSK9 appears to promote the initiation and progression of atherosclerosis. Inhibition of PCSK9 may confer atheroprotection that extends beyond its lipid-lowering effects.
PURPOSE OF REVIEW: Clinical trials with PCSK9 inhibitors have shown a robust decrease in plasma LDL levels and a significant reduction in the incidence of cardiovascular atherosclerotic events. However, the role of PCSK9 in atherosclerosis is not well investigated and it remains unclear whether PCSK9 inhibition has direct, LDL-independent, anti-atherosclerotic effects. This review outlines the molecular pathways and targets of PCSK9 in atherosclerosis and summarizes the experimental and clinical data supporting the anti-atherosclerotic (pleiotropic) actions of PCSK9 inhibitors. RECENT FINDINGS:PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g., endothelial cell, smooth muscle cell, and macrophage) and is detected inside humanatherosclerotic plaque. Preclinical studies have shown that inhibition of PCSK9 can attenuate atherogenesis and plaque inflammation. Besides increasing plasma LDL, PCSK9 appears to promote the initiation and progression of atherosclerosis. Inhibition of PCSK9 may confer atheroprotection that extends beyond its lipid-lowering effects.
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