FAN-CHI CHANGWEN-CHIH CHIANGTsai, Ming-HsuanMing-HsuanTsaiYU-HSIANG CHOUSZU-YU PANChang, Yu-TingYu-TingChangYeh, Pei-YingPei-YingYehYI-TING CHENCHIH-KANG CHIANGYUNG-MING CHENTZONG-SHINN CHUKWAN-DUN WUSHUEI-LIONG LIN2022-09-162022-09-162014-061046-6673https://scholars.lib.ntu.edu.tw/handle/123456789/620856The mechanism of vascular calcification in CKD is not understood fully, but may involve collagen deposition in the arterial wall upon osteo/chondrocytic transformation of vascular smooth muscle cells (VSMCs). Increased levels of circulating angiopoietin-2 correlate with markers of CKD progression and angiopoietin-2 regulate inflammatory responses, including intercellular and vascular adhesion and recruitment of VSMCs. Here, we investigate the potential role of angiopoietin-2 in the pathogenesis of arterial stiffness associated with CKD. In a cohort of 416 patients with CKD, the plasma level of angiopoietin-2 correlated independently with the severity of arterial stiffness assessed by pulse wave velocity. In mice subjected to 5/6 subtotal nephrectomy or unilateral ureteral obstruction, plasma levels of angiopoietin-2 also increased. Angiopoietin-2 expression markedly increased in tubular epithelial cells of fibrotic kidneys but decreased in other tissues, including aorta and lung, after 5/6 subtotal nephrectomy. Expression of collagen and profibrotic genes in aortic VSMCs increased in mice after 5/6 subtotal nephrectomy and in mice producing human angiopoietin-2. Angiopoietin-2 stimulated endothelial expression of chemokines and adhesion molecules for monocytes, increased Ly6C(low) macrophages in aorta, and increased the expression of the profibrotic cytokine TGF-β1 in aortic endothelial cells and Ly6C(low) macrophages. Angiopoietin-2 blockade attenuated expression of monocyte chemokines, profibrotic cytokines, and collagen in aorta of mice after 5/6 subtotal nephrectomy. This study identifies angiopoietin-2 as a link between kidney fibrosis and arterial stiffness. Targeting angiopoietin-2 to attenuate inflammation and collagen expression may provide a novel therapy for cardiovascular disease in CKD.enCHRONIC KIDNEY-DISEASE; SMOOTH-MUSCLE-CELLS; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE; ENDOTHELIAL-CELLS; UNITED-STATES; INFLAMMATION; MORTALITY; TIE2; ATHEROSCLEROSIS[SDGs]SDG3journal article10.1681/ASN.2013050542245111402-s2.0-84906097639WOS:000336558100011https://scholars.lib.ntu.edu.tw/handle/123456789/579268