|Title:||Angiopoietin-2-induced arterial stiffness in CKD||Authors:||???v?H
CHIH-KANG CHIANG|SHUEI-LIONG LIN
|Issue Date:||2014||Journal Volume:||25||Journal Issue:||6||Start page/Pages:||1198-1209||Source:||Journal of the American Society of Nephrology||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. Copyright ? 2014 by the American Society of Nephrology.
|DOI:||10.1681/ASN.2013050542||metadata.dc.subject.other:||angiopoietin 2; transforming growth factor beta1; angiopoietin 1; angiopoietin 2; angiopoietin receptor; ANGPT1 protein, human; Angpt1 protein, mouse; ANGPT2 protein, human; collagen; transcriptome; vasculotropin A; VEGFA protein, human; adult; aged; animal experiment; animal model; aorta; arterial stiffness; Article; chronic kidney disease; collagen gene; controlled study; endothelium cell; epithelium cell; female; gene; gene expression; genetic transcription; human; in vivo study; kidney tubule cell; lung; macrophage; major clinical study; male; mouse; nephrectomy; nonhuman; priority journal; profibrotic gene; protein expression; pulse wave; smooth muscle fiber; ureter obstruction; vascular smooth muscle; vascular smooth muscle cell; animal; article; blood; C57BL mouse; chronic kidney failure; cross-sectional study; disease model; fibrosis; immunology; inflammation; metabolism; middle aged; pathology; physiology; vascular endothelium; Aged; Angiopoietin-1; Angiopoietin-2; Animals; Aorta; Collagen; Cross-Sectional Studies; Disease Models, Animal; Endothelium, Vascular; Female; Fibrosis; Humans; Inflammation; Macrophages; Male; Mice; Mice, Inbred C57BL; Middle Aged; Receptor, TIE-2; Renal Insufficiency, Chronic; Transcriptome; Vascular Endothelial Growth Factor A; Vascular Stiffness
|Appears in Collections:||生理學科所|
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