Antiplatelet Effects of PCSK9 Inhibitors in Primary Hypercholesterolemia

Pęczek, Piotr; Leśniewski, Mateusz; Mazurek, Tomasz; Szarpak, Łukasz; Filipiak‬, Krzysztof J.

doi:10.3390/life11060466

Cited by 17 publications

(15 citation statements)

References 124 publications

(159 reference statements)

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“…As a result, in presence of PSCK9 antibodies, platelet-dependent thrombus formations significantly reduced [68]. Many studies indicate that statins [69] and PCSK9 monoclonal antibodies [70] have an effect on the hemostatic system. In approximately a third of patients, platelets show suboptimal response to antithrombotic therapy that can be linked to hypercholesterolemia [71].…”

Section: Pcsk9 and Platelets' Functionmentioning

confidence: 99%

Non-Lipid Effects of PCSK9 Monoclonal Antibodies on Vessel Wall

Ugovšek

Šebeštjen

2022

JCM

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Elevated low density lipoprotein (LDL) cholesterol and lipoprotein(a) (Lp(a)) levels have an important role in the development and progression of atherosclerosis, followed by cardiovascular events. Besides statins and other lipid-modifying drugs, PCSK9 monoclonal antibodies are known to reduce hyperlipidemia. PCSK9 monoclonal antibodies decrease LDL cholesterol levels through inducing the upregulation of the LDL receptors and moderately decrease Lp(a) levels. In addition, PCSK9 monoclonal antibodies have shown non-lipid effects. PCSK9 monoclonal antibodies reduce platelet aggregation and activation, and increase platelet responsiveness to acetylsalicylic acid. Evolocumab as well as alirocumab decrease an incidence of venous thromboembolism, which is associated with the decrease of Lp(a) values. Besides interweaving in haemostasis, PCSK9 monoclonal antibodies play an important role in reducing the inflammation and improving the endothelial function. The aim of this review is to present the mechanisms of PCSK9 monoclonal antibodies on the aforementioned risk factors.

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Section: Pcsk9 and Platelets' Functionmentioning

confidence: 99%

Non-Lipid Effects of PCSK9 Monoclonal Antibodies on Vessel Wall

Ugovšek

Šebeštjen

2022

JCM

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“…Furthermore, recent studies suggested a novel role for PCSK9 in promoting atherosclerosis through platelet activation, a key role during atherogenesis and in atherothrombosis-induced MI [35,36,[62][63][64]. Notably, several clinical studies have demonstrated the antiplatelet effects of PCSK9 in patients with hypercholesterolemia and found it to be an effective and safe strategy for treating patients with uncontrolled hyperlipidemia and coronary artery disease [65,66].…”

Section: Pcsk9 and MImentioning

confidence: 99%

PCSK9 Promotes Cardiovascular Diseases: Recent Evidence about Its Association with Platelet Activation-Induced Myocardial Infarction

Puteri

Azmi

Kato

et al. 2022

Life

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Cardiovascular diseases are the leading cause of death worldwide, with the majority of the cases being heart failure due to myocardial infarction. Research on cardiovascular diseases is currently underway, particularly on atherosclerosis prevention, to reduce the risk of myocardial infarction. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been reported to play a role in lipid metabolism, by enhancing low-density lipoprotein (LDL) receptor degradation. Therefore, PCSK9 inhibitors have been developed and found to successfully decrease LDL plasma levels. Recent experimental studies have also implicated PCSK9 in platelet activation, having a key role during atherosclerosis progression. Although numerous studies have addressed the role of PCSK9 role in controlling hypercholesterolemia, studies and discussions exploring its involvement in platelet activation are still limited. Hence, here, we address our current understanding of the pathophysiological process involved in atherosclerosis-induced myocardial infarction (MI) through platelet activation and highlight the molecular mechanisms used by PCSK9 in regulating platelet activation. Undoubtedly, a deeper understanding of the relationship between platelet activation and the underlying molecular mechanisms of PCSK9 in the context of MI progression will provide a new strategy for developing drugs that selectively inhibit the most relevant pathways in cardiovascular disease progression.

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“…CD46 and LOX-1 are involved in them [ 69 , 70 ] and, accompanied by ox-LDL binding protein, play a key role in the formation of blood clots [ 71 ]. A separate mechanism is associated with the toll-like receptor 2 (TLR-2) stimulation, which activates the process of platelet aggregation through lipid-peroxide-modified phospholipids in the transport of Lp(a) [ 72 , 73 , 74 ].…”

Section: Pcsk9 and Atherosclerosismentioning

confidence: 99%

Insight into the Evolving Role of PCSK9

et al. 2022

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the last discovered member of the family of proprotein convertases (PCs), mainly synthetized in hepatic cells. This serine protease plays a pivotal role in the reduction of the number of low-density lipoprotein receptors (LDLRs) on the surface of hepatocytes, which leads to an increase in the level of cholesterol in the blood. This mechanism and the fact that gain of function (GOF) mutations in PCSK9 are responsible for causing familial hypercholesterolemia whereas loss-of-function (LOF) mutations are associated with hypocholesterolemia, prompted the invention of drugs that block PCSK9 action. The high efficiency of PCSK9 inhibitors (e.g., alirocumab, evolocumab) in decreasing cardiovascular risk, pleiotropic effects of other lipid-lowering drugs (e.g., statins) and the multifunctional character of other proprotein convertases, were the cause for proceeding studies on functions of PCSK9 beyond cholesterol metabolism. In this article, we summarize the current knowledge on the roles that PCSK9 plays in different tissues and perspectives for its clinical use.

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Antiplatelet Effects of PCSK9 Inhibitors in Primary Hypercholesterolemia

Cited by 17 publications

References 124 publications

Non-Lipid Effects of PCSK9 Monoclonal Antibodies on Vessel Wall

Non-Lipid Effects of PCSK9 Monoclonal Antibodies on Vessel Wall

PCSK9 Promotes Cardiovascular Diseases: Recent Evidence about Its Association with Platelet Activation-Induced Myocardial Infarction

Insight into the Evolving Role of PCSK9

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