PCSK9, a promising novel target for age-related cardiovascular dysfunction

Cardiovascular diseases (CVD) are the leading cause of death among elderly people. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator of cholesterol metabolism. Herein, we investigated the role of PCSK9 in age-related CVD. Both in humans and rats, sPCSK9 correlated positively with increasing age and the development of cardiovascular dysfunction. Network analysis identified PCSK9 as an important factor in age-associated lipid alterations and it correlated positively with intima media thickness, a clinical parameter of CVD risk. PCSK9 inhibition with alirocumab effectively reduced the CVD progression in aging rats suggesting that PCSK9 plays an important role in cardiovascular aging.心血管疾病（Cardiovascular Diseases, CVD）是老年群体致死的首要病因。前蛋白转化酶枯草溶菌素/kexin9型（Proprotein Convertase Subtilisin/Kexin Type 9, PCSK9）是胆固醇代谢的重要调控因子。本研究探究了PCSK9在年龄相关性心血管疾病中的作用。在人类与大鼠体内，可溶性PCSK9（soluble PCSK9, sPCSK9）均随年龄增长及心血管功能障碍的发生发展呈正相关。网络分析结果显示，PCSK9是年龄相关性脂质代谢异常的关键调控因子，且其与心血管疾病风险的临床评估指标——内膜中层厚度（intima media thickness）呈正相关。使用阿利西尤单抗（alirocumab）抑制PCSK9可有效减缓衰老大鼠的心血管疾病进展，这表明PCSK9在心血管衰老过程中发挥着重要作用。