Interaction between PCSK9 and lipid levels in ART-untreated patients with either HIV/HCV coinfection or HIV infection alone

PCSK9 is a soluble member of the mammalian proprotein convertase family of serine proteases (1), which is synthesized and secreted mainly by the liver (1). At transcriptional level PCSK9 synthesis is regulated by the Hepatocyte Nuclear Factor-1α (HNF1α), and by the Sterol Regulatory Element-Binding Protein-2 (SREBP-2)(2,3). PCSK9 is a key regulator of cholesterol homeostasis that controls low-density lipoprotein receptor (LDLR) density on the surface of hepatocytes and promotes LDLR degradation both at the intracellular and extracellular level. Gain of function mutations of the gene encoding for PCSK9 were associated with increased LDL cholesterol levels and cardiovascular risk. Hence, PCSK9 is considered a possible marker of cardiovascular risk (2). Dyslipidemia is common in HIV+ patients and likely contributes to the high cardiovascular risk (4-7). Higher plasma PCSK9 levels have been found in HAART-treated and untreated HIV+ patients (8) and despite PCSK9 levels were increased in this population, lower cholesterol levels have been also documented. This paradox has been observed also in patients with HIV and HCV coinfection. In order to better examine the pathophysiological connection between PCSK9 and HIV-HCV infection, a more in depth evaluation of those mechanisms controlling cholesterol metabolism are warranted possibly eliminating the interference of putative confounders, including ART, which has been associated with disturbances of lipid metabolism

elisabetta schiaroli
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