Hypercholesterolemia is a major risk factor for atherosclerosis. Low-density lipoprotein cholesterol (LDL-C) lowering drugs reduce cardiovascular morbidity and mortality. However, many individuals treated with statins do not achieve their target levels of LDL-C. So, there is great need for new drugs to reduce cholesterol in those patients who have not achieved target levels with statins as well as those who are statin intolerant. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel agent, which plays an important role in the regulation of cholesterol metabolism. It increases degradation of the low-density lipoprotein receptor, modulates cholesterol metabolism, and transport. This review will address new therapeutic strategies targeting PCSK9, including monoclonal antibodies, small interfering RNAs, and other small molecule inhibitors.
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PCSK9 in T-cell function and the immune response.
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) was first reported in 2003 and confirmed to be strongly associated with familial hypercholesterolemia. Small-molecule inhibitors targeting PCSK9 provide an effective and safe method for managing hypercholesterolemia and reducing the cardiovascular risk. In recent years, increasing evidence has indicated other important roles for PCSK9 in inflammation, tumors, and even immune regulation.
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Background: The co-occurrence of pulmonary hypertension (PH) in patients with pulmonary fibrosis (PF) is linked to a more unfavorable prognosis and increased mortality compared to PF cases without PH. Early intervention and comprehensive management are pivotal for improving survival outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein essential in cholesterol metabolism.
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Institute of Lipid Metabolism and Atherosclerosis, School of Pharmacy, Shandong Second Medical University, Weifang 261053, China. Electronic address:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is known to promote hyperlipidemia primarily by inducing the degradation of the low-density lipoprotein receptor. Notably, recent studies have demonstrated that PCSK9 promotes inflammation in the vascular system, however, the roles of PCSK9 in hepatic inflammation remain unclear. As PCSK9 is primarily expressed in the liver, this study aimed to elucidate the roles of PCSK9 and the underlying mechanisms in lipopolysaccharide (LPS)-challenged hepatocytes.
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