McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA.
Division of Cardiology, University of North Carolina, Chapel Hill, NC, 27599-7075, USA.
Sci Rep. 2021 Feb 11;11(1):3606. doi: 10.1038/s41598-021-81646-1.
Cyr61 is a member of the CCN family of proteins that is expressed in atherosclerotic lesions and regulated by angiotensin II. It is unknown whether renal artery stenosis (RAS) increases Cyr61 expression. Male ApoE mice were randomized to surgically induced RAS, RAS + treatment with either irbesartan, aliskiren or amlodipine or sham-surgery. RAS resulted in increased plasma angiotensin II levels, a mild, sustained increase in systolic blood pressure and increased aortic lipid deposition compared to sham-surgery. Surgically induced RAS led to the formation of atheroma in the infrarenal aorta and there was consistent and intense staining for Cyr61 within the atheroma. Treatment with irbesartan, aliskiren and amlodipine were associated with decreased aortic lipid deposition and decreased staining for Cyr61 in aortic atheroma. Serum levels of Cyr61 were not increased in mice or humans with RAS. In summary, Cyr61 expression in aortic atheroma but not serum is increased by RAS in ApoE mice and is reduced by agents that lower blood pressure.
Cyr61 是富含半胱氨酸的酸性分泌蛋白（CCN）家族的一员，在动脉粥样硬化病变中表达，并受血管紧张素 II 调节。目前尚不清楚肾动脉狭窄（RAS）是否会增加 Cyr61 的表达。雄性载脂蛋白 E （ApoE）小鼠被随机分为手术诱导的 RAS 组、RAS+用厄贝沙坦、阿利克仑或氨氯地平治疗组或假手术组。与假手术组相比，RAS 导致血浆血管紧张素 II 水平升高、收缩压轻度持续升高以及主动脉脂质沉积增加。手术诱导的 RAS 导致肾下腹主动脉粥样硬化的形成，并且在动脉粥样硬化中 Cyr61 有一致且强烈的染色。厄贝沙坦、阿利克仑和氨氯地平治疗与主动脉脂质沉积减少和主动脉粥样硬化中 Cyr61 染色减少有关。RAS 小鼠或人类的血清 Cyr61 水平没有升高。综上所述，在 ApoE 小鼠中，RAS 会增加主动脉粥样硬化中 Cyr61 的表达，但不会增加血清 Cyr61 水平，而降低血压的药物可减少 Cyr61 的表达。
