2979The effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors on endothelial progenitor cells

Abstract

Abstract Background Endothelial progenitor cells (EPCs) have an important role in the process of vascular repair by promoting re-endothelialization following endothelial injury. We hypothesized that proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors, which reduce cardiovascular events, will increase the level of EPCs and thus affect the process of vascular repair. Therefore, we sought to investigate the effect of PCSK9 inhibitors on circulating EPCs. Methods Study population included patients with known stable CAD who were initiated PCSK9 inhibitors. Blood samples were drawn and evaluated for EPCs at baseline and after treatment (1 month). Circulating EPCs were then assessed quantitatively by the expression of VEGFR-2, CD34 and CD133 using flow cytometry, and functionally by the formation of colony forming units (CFUs). Results Our preliminary cohort included 12 patients (median age of 69 years), 31% of whom were female. At baseline, total cholesterol and low density lipoprotein levels were 190 (IQR 180, 227) mg/dL and 123 (IQR 107, 154) mg/dL, respectively. Following 1-month of therapy with a PCSK9 inhibitor and along with a decrease in LDL to a median of 58 (IQR 50, 67) mg/dL, we observed an increase in the expression of CD34(+)/VEGFR-2(+) (1.2% (IQR 0.6, 1.6) to 3.0% (IQR 1.2, 4.5), P=0.07) and CD133(+)/VEGFR-2(+) (0.8% (IQR 0.7, 1.4) to 1.7% (IQR 0.6, 4.0), P=0.5). Proliferation of EPCs was confirmed microscopically (1 CFUs (IQR 1, 1.5) to 1.5 CFUs (IQR 1.5, 2.5), P=0.016) (Figure 1) and by an MTT assay (0.16 (IQR 0.12, 0.19) to 0.19 (IQR 0.17, 0.21), p=0.016). Conclusions These preliminary results in patients with CAD demonstrate that treatment with PCSK9 inhibitors is associated with higher levels of EPCs, thus promote endothelial repair. This finding may represent a novel mechanism of action of PCSK9 inhibitors, which might have important future clinical implications.