| First Author | Menendez-Castro C | Year | 2015 |
| Journal | J Pathol | Volume | 236 |
| Issue | 1 | Pages | 5-16 |
| PubMed ID | 25511181 | Mgi Jnum | J:220611 |
| Mgi Id | MGI:5635735 | Doi | 10.1002/path.4501 |
| Citation | Menendez-Castro C, et al. (2015) Under-expression of alpha8 integrin aggravates experimental atherosclerosis. J Pathol 236(1):5-16 |
| abstractText | Integrins play an important role in vascular biology. The alpha8 integrin chain attenuates smooth muscle cell migration but its functional role in the development of atherosclerosis is unclear. Therefore, we studied the contribution of alpha8 integrin to atherosclerosis and vascular remodelling. We hypothesized that alpha8 integrin expression is reduced in atherosclerotic lesions, and that its under-expression leads to a more severe course of atherosclerosis. alpha8 Integrin was detected by immunohistochemistry and qPCR and alpha8 integrin-deficient mice were used to induce two models of atherosclerotic lesions. First, ligation of the carotid artery led to medial thickening and neointima formation, which was quantified in carotid cross-sections. Second, after crossing into ApoE-deficient mice, the formation of advanced vascular lesions with atherosclerotic plaques was quantified in aortic en face preparations stained with Sudan IV. Parameters of renal physiology and histopathology were assessed: alpha8 integrin was detected in the media of human and murine vascular tissue and was down-regulated in arteries with advanced atherosclerotic lesions. In alpha8 integrin-deficient mice (alpha8(-/-) ) as well as alpha8(+/-) and alpha8(+/+) littermates, carotid artery ligation increased media:lumen ratios in all genotypes, with higher values in ligated alpha8(-/-) and alpha8(+/-) compared to ligated alpha8(+/+) animals. Carotid artery ligation increased smooth muscle cell number in the media of alpha8(+/+) mice and, more prominently, of alpha8(-/-) or alpha8(+/-) mice. On an ApoE(-/-) background, alpha8(+/-) and alpha8(-/-) mice developed more atherosclerotic plaques than alpha8(+/+) mice. alpha8 Integrin expression was reduced in alpha8(+/-) animals. Renal damage with increased serum creatinine and glomerulosclerosis was detected in alpha8(-/-) mice only. Thus, under-expression of alpha8 integrin aggravates vascular lesions, while a complete loss of alpha8 integrin results in reduced renal mass and additional renal disease in the presence of generalized atherosclerosis. Our data support the hypothesis that integrin alpha8beta1 has a protective role in arterial remodelling and atherosclerosis. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
