https://scholars.lib.ntu.edu.tw/handle/123456789/620856
標題: | Angiopoietin-2-induced arterial stiffness in CKD | 作者: | FAN-CHI CHANG WEN-CHIH CHIANG Tsai, Ming-Hsuan YU-HSIANG CHOU SZU-YU PAN Chang, Yu-Ting Yeh, Pei-Ying YI-TING CHEN CHIH-KANG CHIANG YUNG-MING CHEN TZONG-SHINN CHU KWAN-DUN WU SHUEI-LIONG LIN |
關鍵字: | CHRONIC KIDNEY-DISEASE; SMOOTH-MUSCLE-CELLS; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE; ENDOTHELIAL-CELLS; UNITED-STATES; INFLAMMATION; MORTALITY; TIE2; ATHEROSCLEROSIS | 公開日期: | 六月-2014 | 出版社: | AMER SOC NEPHROLOGY | 卷: | 25 | 期: | 6 | 起(迄)頁: | 1198 | 來源出版物: | Journal of the American Society of Nephrology : JASN | 摘要: | The 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/620856 | ISSN: | 1046-6673 | DOI: | 10.1681/ASN.2013050542 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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