Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), Via Luigi Polacchi, Chieti, Italy.
Mediterranea Cardiocentro, Napoli, Italy.
Sci Rep. 2021 May 6;11(1):9659. doi: 10.1038/s41598-021-88941-x.
Protease proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL cholesterol clearance and has been associated with cardiovascular risk. PCSK9 inhibitors increase in vivo circulating endothelial progenitor cells (EPCs), a subtype of immature cells involved in ongoing endothelial repair. We hypothesized that the effect of PCSK9 on vascular homeostasis may be mediated by EPCs in patients with or without type 2 diabetes mellitus (T2DM). Eighty-two patients (45 with, 37 without T2DM) at high cardiovascular risk were enrolled in this observational study. Statin treatment was associated with higher circulating levels of PCSK9 in patients with and without T2DM (p < 0.001 and p = 0.036) and with reduced CD45/CD34 (total EPC compartment) (p = 0.016) and CD45/CD34/CD146 (early EPC) (p = 0.040) only among patients with T2DM. In the whole group of patients, statin treatment was the only independent predictor of low number of CD45/CD34 (β = - 0.230; p = 0.038, adjusted R = 0.041). Among T2DM patients, PCSK9 circulating levels were inversely related and predicted both the number of CD45/CD34 (β = - 0.438; p = 0.003, adjusted R = 0.173), and CD45/CD34/CD146 (β = - 0.458; p = 0.002, adjusted R = 0.191) independently of age, gender, BMI and statin treatment. In high-risk T2DM patients, high endogenous levels of PCSK9 may have a detrimental effect on EPCs by reducing the endothelial repair and worsening the progression of atherothrombosis.
蛋白酶原转化酶枯草溶菌素 9（PCSK9）是一种 LDL 胆固醇清除的调节剂，与心血管风险相关。PCSK9 抑制剂增加体内循环内皮祖细胞（EPC）的数量，EPC 是一种参与持续内皮修复的未成熟细胞亚型。我们假设，PCSK9 对血管稳态的影响可能通过有或没有 2 型糖尿病（T2DM）的患者中的 EPC 来介导。这项观察性研究纳入了 82 名高心血管风险患者（45 名患有 T2DM，37 名未患有 T2DM）。他汀类药物治疗与患有和不患有 T2DM 的患者的循环 PCSK9 水平升高相关（p < 0.001 和 p = 0.036），并与 CD45/CD34（总 EPC 区室）（p = 0.016）和 CD45/CD34/CD146（早期 EPC）（p = 0.040）减少相关，仅在患有 T2DM 的患者中如此。在所有患者中，他汀类药物治疗是 CD45/CD34 数量减少的唯一独立预测因子（β = -0.230；p = 0.038，调整后的 R = 0.041）。在 T2DM 患者中，循环 PCSK9 水平与 CD45/CD34 的数量呈负相关，且独立于年龄、性别、BMI 和他汀类药物治疗预测 CD45/CD34（β = -0.438；p = 0.003，调整后的 R = 0.173）和 CD45/CD34/CD146（β = -0.458；p = 0.002，调整后的 R = 0.191）的数量。在高危 T2DM 患者中，内源性 PCSK9 水平升高可能通过减少内皮修复和加重动脉粥样血栓形成的进展对 EPC 产生有害影响。
