Abstract Number: PB0076
Meeting: ISTH 2020 Congress
Background: Protease proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of low-density lipoprotein (LDL)-cholesterol clearance and has been associated with cardiovascular disease risk, platelet function and blood coagulation. PCSK9 knockout mice develop less venous and arterial thrombosis and show reduced in vivo platelet activation upon arterial injury. In vivo PCSK9 inhibitors, besides the cholesterol-lowering effect, increase circulating endothelial progenitor cells (cEPCs). cEPCs are a subtype of immature cells with a role in ongoing endothelial repair. EPC administration accelerates the resolution of arterial thrombus in mice while their depletion may contribute to endothelial dysfunction and cardiovascular disease progression. Circulating CD34bright and their subpopulation CD34bright/CD146– cells include both mature Endothelial Cells (ECs) and EPCs.
Aims: The aim of this study was to evaluate whether the effect of PCSK9 on vascular homeostasis and atherothrombosis may be mediated by EPC in patients with or without Type 2 Diabetes Mellitus (T2DM).
Methods: Fifty-five patients (33 with and 22 without T2DM) were enrolled at the Diabetes Clinics of Chieti University Hospitals. All patients were treated with low dose ASA (100 mg day) for cardiovascular prevention. Twelve had a previous myocardial infarction. Plasma PCSK9 was measured by enzyme-linked immunosorbent assays (ELISA) (#DPC900, R&D). Circulating CD34bright and CD34bright/CD146– cells were analyzed by a standardized flow cytometry method.
Results: PCSK9 levels were comparable between patients with or without T2DM. Circulating CD34bright and CD34bright/CD146– cells were significantly lower in patients with T2DM (p=0.018 and p=0.039 respectively). Patients with a previous myocardial infarction had higher levels of PCSK9 (p=0.006) and lower levels of circulating CD34bright/CD146– (p=0.016). Only in patients with T2DM, PCSK9 correlated inversely with both CD34bright (Rho=-0.442, p=0.010) and CD34bright/CD146– (Rho=-0.480, p=0.005).
Conclusions: Our results suggest that in high-risk patients with T2DM, endogenous levels of PCSK9 may have a detrimental effect on CD34bright/CD146– by reducing the endothelial repair and worsening the progression of atherothrombosis.
To cite this abstract in AMA style:Tripaldi R, Simeone PGM, Lanuti P, Liani R, Ciotti S, Cipollone F, Marchisio M, Santilli F. Endogenous PCSK9 Is Related to Circulating CD34bright/CD146– Cells in Patients with Type 2 Diabetes Mellitus [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/endogenous-pcsk9-is-related-to-circulating-cd34bright-cd146-cells-in-patients-with-type-2-diabetes-mellitus/. Accessed January 28, 2022.
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