PCSK9 and inflammation: a review of experimental and clinical evidence

Abstract

Proprotein convertase subtilisin/kexin Type 9 (PCSK9) is now identified as an important and major player in hypercholesterolaemia and atherosclerosis pathophysiology. PCSK9, through promoting lysosomal degradation of hepatic low-density lipoprotein (LDL) receptor, can decrease the clearance of plasma LDLs, leading to hypercholesterolaemia and consequent atherosclerotic plaque formation. Hypercholesterolaemia has been found to promote systemic and vascular inflammation, which can cause atherosclerotic lesion formation and progression and subsequent incidence of cardiovascular disease. Recent studies have shown the involvement of PCSK9 in the inflammatory pathway of atherosclerosis. Although trials with PCSK9 inhibitors have not shown any alteration in plasma C-reactive protein levels, there is accumulating evidence showing lessened inflammatory response in the arterial wall that could attenuate atherosclerotic plaque development beyond the established LDL-lowering effect of PCSK9 inhibition. In this review, we represent mounting evidence indicating that PCSK9 can locally increase vascular inflammation and contribute to atherosclerotic plaque progression in patients with hypercholesterolaemia.

<p>Is PCSK9 Associated with Plasma Lipid Levels in a Sub-Saharan African Population of Patients with Obesity and Type 2 Diabetes?</p>

“…It has been shown to be positively correlated with hs-CRP which is also an independent cardiovascular disease (CVD) risk marker. 7 Our data indicate that hs-CRP levels differed significantly among the 3 groups but there was no correlation between PCSK9 and hs-CRP.…”

“…5,6 Moreover, observational studies suggest a weak positive correlation between PCSK9 and CRP, but a recent review revealed that PCSK9 inhibitors do not alter hs-CRP levels. 6,7 There are inconsistent findings in the association between PCSK9 measured in ethnically diverse cohorts and plasma LDL concentrations. Some studies found PCSK9 level elevated in patients with obesity and T2D and others not.…”

Lipid-lowering therapy and renin-angiotensin-aldosterone system inhibitors in the era of the COVID-19 pandemic

“…In this context, there are no premises that PCSK9 inhibitors, because they are monoclonal antibodies (in relation to the above-mentioned high cytokine storm during infection), should be discontinued. In contrast, PCSK9 inhibitors should be continued to achieve further low-density lipoprotein cholesterol (LDL-C) lowering (based on "the lower, the better" principle), because then we might significantly stabilise atheroma plaque, reduce the risk of CVD events, and reduce inflammation [46][47][48]. Recent available data have confirmed the role of PCSK9 inhibition in reducing the process of inflammation via decreasing main vascular inflammatory markers, reducing infiltration of monocytes into the subendothelial layer, and inhibiting monocyte migration.…”

“…Recent available data have confirmed the role of PCSK9 inhibition in reducing the process of inflammation via decreasing main vascular inflammatory markers, reducing infiltration of monocytes into the subendothelial layer, and inhibiting monocyte migration. Apart from the reduction of pro-inflammatory mediators, PCSK9 inhibitors could ameliorate vascular inflammation [47]. Finally, a direct local anti-inflammatory action of PCSK9 inhibitors, independent of LDL-C reduction, has been shown in animal models; however, it still merits further investigation [47,48].…”

“…Apart from the reduction of pro-inflammatory mediators, PCSK9 inhibitors could ameliorate vascular inflammation [47]. Finally, a direct local anti-inflammatory action of PCSK9 inhibitors, independent of LDL-C reduction, has been shown in animal models; however, it still merits further investigation [47,48].…”