Abstract：
The focus of this article is to highlight the importance of the small GTPase, Ras-associated protein 1 (Rap1), in proprotein convertase subtilisin/kexin type 9 (PCSK9) regulation and atherosclerosis and type 2 diabetes etiology and discuss the potential therapeutic implications of targeting Rap1 in these disease areas.
Cardiometabolic disease characterized by obesity, glucose intolerance, dyslipidemia, and atherosclerotic cardiovascular disease remain an important cause of mortality. Evidence using mouse models of obesity and insulin resistance indicates that Rap1 deficiency increases proatherogenic PCSK9 and low-density lipoprotein cholesterol levels and predisposes these mice to develop obesity- and statin-induced hyperglycemia, which highlights Rap1\'s role in cardiometabolic dysfunction. Rap1 may also contribute to cardiovascular disease through its effects on vascular wall cells involved in the atherosclerosis progression. Rap1 activation, specifically in the liver, could be beneficial in the prevention of cardiometabolic perturbations, including type 2 diabetes, hypercholesterolemia, and atherosclerosis.
Cardiometabolic disease characterized by obesity, glucose intolerance, dyslipidemia, and atherosclerotic cardiovascular disease remain an important cause of mortality. Evidence using mouse models of obesity and insulin resistance indicates that Rap1 deficiency increases proatherogenic PCSK9 and low-density lipoprotein cholesterol levels and predisposes these mice to develop obesity- and statin-induced hyperglycemia, which highlights Rap1\'s role in cardiometabolic dysfunction. Rap1 may also contribute to cardiovascular disease through its effects on vascular wall cells involved in the atherosclerosis progression. Rap1 activation, specifically in the liver, could be beneficial in the prevention of cardiometabolic perturbations, including type 2 diabetes, hypercholesterolemia, and atherosclerosis.
摘要：
目的：本文的重点是强调小GTP酶的重要性，Ras相关蛋白1（Rap1），在前蛋白转化酶枯草杆菌蛋白酶/kexin9型（PCSK9）的调节和动脉粥样硬化和2型糖尿病的病因，并讨论在这些疾病领域靶向Rap1的潜在治疗意义。
结果：以肥胖为特征的心血管疾病，葡萄糖不耐受,血脂异常,动脉粥样硬化性心血管疾病仍然是死亡的重要原因。使用肥胖和胰岛素抵抗小鼠模型的证据表明，Rap1缺乏会增加致动脉粥样硬化的PCSK9和低密度脂蛋白胆固醇水平，并使这些小鼠容易发生肥胖和他汀类药物引起的高血糖，这突出了Rap1在心脏代谢功能障碍中的作用。Rap1还可能通过其对参与动脉粥样硬化进展的血管壁细胞的影响而导致心血管疾病。Rap1激活,特别是在肝脏中，可能有助于预防心脏代谢紊乱，包括2型糖尿病,高胆固醇血症,和动脉粥样硬化。
结果：以肥胖为特征的心血管疾病，葡萄糖不耐受,血脂异常,动脉粥样硬化性心血管疾病仍然是死亡的重要原因。使用肥胖和胰岛素抵抗小鼠模型的证据表明，Rap1缺乏会增加致动脉粥样硬化的PCSK9和低密度脂蛋白胆固醇水平，并使这些小鼠容易发生肥胖和他汀类药物引起的高血糖，这突出了Rap1在心脏代谢功能障碍中的作用。Rap1还可能通过其对参与动脉粥样硬化进展的血管壁细胞的影响而导致心血管疾病。Rap1激活,特别是在肝脏中，可能有助于预防心脏代谢紊乱，包括2型糖尿病,高胆固醇血症,和动脉粥样硬化。
