PCSK9 Relationship with LDL and LDLR: A Promising Method for Treatment of Dyslipidemia

Background: One of the most significant risk factors for cardiovascular (CV) disease is dyslipidemia, exacerbated atherosclerosis, and premature mortality due to heart attack. Lipid disorders have several etiologies, categorized into primary and secondary types. PCSK9 serves as a crucial target for treating hyperlipidemia, not only because of its recent identification or the novel biological insights it has offered, but also due to significant scientific progress that has rapidly led to effective therapeutic applications. Hepatic PCSK9 is a significant circulating protein that regulates the half-life of both the VLDLR and the LDLR. Inhibiting it is considered to be one of the most cutting-edge and technologically advanced new treatment techniques for successfully decreasing LDL cholesterol levels. Statins are the drug of choice for most cases, even though some patients do not respond to statins even with high doses. Objective: The major aim of this study is to highlight the role of PCSK9 in regulating LDL and LDLR and the effect of statins, along with PCSK9 inhibitors, on LDL and LDLR and lipid profile in general. Method: To find pertinent trials regarding PCSK9’s relation to hyperlipidemia and statin therapy between 2000 and 2024, the search strategy used electronic databases such as PubMed, Web of Science, Springer, Google Scholar, and others. Conclusion: The main kinds of frequently administered lipid-lowering drugs have been shown to raise serum PCSK9 levels. These findings most likely explain why these medicines are not more successful in lowering LDL-C and indicate that research should be done to create novel drugs that lower LDL-C by either lowering or inhibiting PCSK9 or by not raising circulating PCSK9 levels.