Angiopoietin-2-induced arterial stiffness in CKD
Journal
Journal of the American Society of Nephrology : JASN
Journal Volume
25
Journal Issue
6
Pages
1198
Date Issued
2014-06
Author(s)
Tsai, Ming-Hsuan
Chang, Yu-Ting
Yeh, Pei-Ying
Abstract
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.
Subjects
CHRONIC KIDNEY-DISEASE; SMOOTH-MUSCLE-CELLS; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE; ENDOTHELIAL-CELLS; UNITED-STATES; INFLAMMATION; MORTALITY; TIE2; ATHEROSCLEROSIS
SDGs
Publisher
AMER SOC NEPHROLOGY
Type
journal article