Key result
PCSK9 promotes atherothrombosis and MI through direct platelet activation, independent of lipid effects.
Why the study?
Although PCSK9's role in hypercholesterolemia is well-studied, research and discussion exploring its involvement in platelet activation remain limited.
Understanding PCSK9's pleiotropic role in platelet activation provides a mechanistic rationale for using PCSK9 inhibitors to potentially reduce atherothrombotic events beyond simple LDL reduction.
May support PCSK9 inhibitor trials targeting platelet effects; leaves open clinical relevance beyond LDL lowering.
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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Puteri et al. (2022) conducted a review in Atherosclerosis and Myocardial Infarction. PCSK9 was evaluated. Recent evidence suggests PCSK9 promotes atherothrombosis and myocardial infarction through direct induction of platelet activation, independently of its lipid-lowering effects.
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