Angiopoietin-2-induced arterial stiffness in CKD

Fan Chi Chang, Wen Chih Chiang, Ming Hsuan Tsai, Yu Hsiang Chou, Szu Yu Pan, Yu Ting Chang, Pei Ying Yeh, Yi Ting Chen, Chih Kang Chiang, Yung Ming Chen, Tzong Shinn Chu, Kwan Dun Wu, Shuei Liong Lin

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Themechanismof vascular calcification in CKDis not understood fully, butmay involve collagen deposition in the arterial wall upon osteo/chondrocytic transformation of vascular smoothmuscle 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 bypulse wave velocity. Inmice subjected to 5/6 subtotal nephrectomyor 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 inmice after 5/6 subtotal nephrectomy and inmice producing human angiopoietin-2. Angiopoietin-2 stimulated endothelial expression of chemokines and adhesion molecules for monocytes, increased Ly6Clow macrophages in aorta, and increased the expression of the profibrotic cytokine TGF-β1 in aortic endothelial cells and Ly6Clow 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.

Original languageEnglish
Pages (from-to)1198-1209
Number of pages12
JournalJournal of the American Society of Nephrology
Issue number6
Publication statusPublished - Jun 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)


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