In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 289, No. 2 ( 2005-08), p. H845-H851
Abstract:
Accumulating clinical evidence indicates increased aortic stiffness, an independent risk factor for cardiovascular and all-cause mortality, in type 2 diabetic and glucose-intolerant individuals. The present study sought to determine whether increased mechanical stiffness, an altered extracellular matrix, and a profibrotic gene expression profile could be observed in the aorta of the insulin-resistant Zucker fa/fa rat. Mechanical testing of Zucker fa/fa aortas showed increased vascular stiffness in longitudinal and circumferential directions compared with Zucker lean controls. Unequal elevations in developed strain favoring the longitudinal direction resulted in a loss of anisotropy. Real-time quantitative PCR and immunohistochemistry revealed increased expression of fibronectin and collagen IVα 3 in the Zucker fa/fa aorta. In addition, expression of transforming growth factor-β and several Smad proteins was increased in vessels from insulin-resistant animals. In rat vascular smooth muscle cells, 12–18 h of exposure to insulin (100 nmol/l) enhanced transforming growth factor-β1 mRNA expression, implicating a role for hyperinsulinemia in vascular stiffness. Thus there is mechanical, structural, and molecular evidence of arteriosclerosis in the Zucker fa/fa rat at the glucose-intolerant, hyperinsulinemic stage.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00134.2005
Language:
English
Publisher:
American Physiological Society
Publication Date:
2005
detail.hit.zdb_id:
1477308-9
SSG:
12
