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  • Title: The role of proprotein convertase subtilisin/kexin type 9 in hyperlipidemia: focus on therapeutic implications.
    Author: Farnier M.
    Journal: Am J Cardiovasc Drugs; 2011 Jun 01; 11(3):145-52. PubMed ID: 21619378.
    Abstract:
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of circulating levels of low-density lipoprotein (LDL) particles. PCSK9 acts mainly by enhancing degradation of the LDL receptor in the liver. Several gain-of-function and loss-of-function mutations in the PCSK9 gene have been identified and linked to hypercholesterolemia and hypocholesterolemia, respectively. Since the loss-of-function mutations in humans are associated with protection against coronary heart disease, and with no apparent deleterious effects, PCSK9 inhibition is becoming attractive as a new strategy for lowering LDL cholesterol (LDL-C) levels, particularly in combination with statins. Candidate patient populations for PCSK9 inhibition include those with familial hypercholesterolemia, patients at high risk of cardiovascular disease not controlled by statin therapy, and patients with poor tolerance or total intolerance to statin therapy. PCSK9 inhibition represents a very promising target for reducing LDL-C levels and decreasing the risk of atherosclerotic cardiovascular diseases, but human clinical trials will be crucial to assess the potency and safety of PCSK9 inhibitors.
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