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 journalArticle

17 Citations (Scopus)

Abstract

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
Volume25
Issue number6
DOIs
Publication statusPublished - Jun 1 2014
Externally publishedYes

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Angiopoietin-2
Vascular Stiffness
Blood Vessels
Collagen
Nephrectomy
Aorta
Chemokines
Monocytes
Macrophages
Cytokines
Vascular Calcification
Kidney
Ureteral Obstruction
Fibrosis
Cardiovascular Diseases
Endothelial Cells
Epithelial Cells

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Chang, F. C., Chiang, W. C., Tsai, M. H., Chou, Y. H., Pan, S. Y., Chang, Y. T., ... Lin, S. L. (2014). Angiopoietin-2-induced arterial stiffness in CKD. Journal of the American Society of Nephrology, 25(6), 1198-1209. https://doi.org/10.1681/ASN.2013050542

Angiopoietin-2-induced arterial stiffness in CKD. / Chang, Fan Chi; Chiang, Wen Chih; Tsai, Ming Hsuan; Chou, Yu Hsiang; Pan, Szu Yu; Chang, Yu Ting; Yeh, Pei Ying; Chen, Yi Ting; Chiang, Chih Kang; Chen, Yung Ming; Chu, Tzong Shinn; Wu, Kwan Dun; Lin, Shuei Liong.

In: Journal of the American Society of Nephrology, Vol. 25, No. 6, 01.06.2014, p. 1198-1209.

Research output: Contribution to journalArticle

Chang, FC, Chiang, WC, Tsai, MH, Chou, YH, Pan, SY, Chang, YT, Yeh, PY, Chen, YT, Chiang, CK, Chen, YM, Chu, TS, Wu, KD & Lin, SL 2014, 'Angiopoietin-2-induced arterial stiffness in CKD', Journal of the American Society of Nephrology, vol. 25, no. 6, pp. 1198-1209. https://doi.org/10.1681/ASN.2013050542
Chang FC, Chiang WC, Tsai MH, Chou YH, Pan SY, Chang YT et al. Angiopoietin-2-induced arterial stiffness in CKD. Journal of the American Society of Nephrology. 2014 Jun 1;25(6):1198-1209. https://doi.org/10.1681/ASN.2013050542
Chang, Fan Chi ; Chiang, Wen Chih ; Tsai, Ming Hsuan ; Chou, Yu Hsiang ; Pan, Szu Yu ; Chang, Yu Ting ; Yeh, Pei Ying ; Chen, Yi Ting ; Chiang, Chih Kang ; Chen, Yung Ming ; Chu, Tzong Shinn ; Wu, Kwan Dun ; Lin, Shuei Liong. / Angiopoietin-2-induced arterial stiffness in CKD. In: Journal of the American Society of Nephrology. 2014 ; Vol. 25, No. 6. pp. 1198-1209.
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