| First Author | Manrique-Acevedo C | Year | 2017 |
| Journal | Endocrinology | Volume | 158 |
| Issue | 6 | Pages | 1875-1885 |
| PubMed ID | 28430983 | Mgi Jnum | J:245195 |
| Mgi Id | MGI:5914114 | Doi | 10.1210/en.2016-1831 |
| Citation | Manrique-Acevedo C, et al. (2017) Absence of Endothelial ERalpha Results in Arterial Remodeling and Decreased Stiffness in Western Diet-Fed Male Mice. Endocrinology 158(6):1875-1885 |
| abstractText | The role of estrogen receptor-alpha (ERalpha) signaling in the vasculature of females has been described under different experimental conditions and our group recently reported that lack of endothelial cell (EC) ERalpha in female mice fed a Western diet (WD) results in amelioration of vascular stiffness. Conversely, the role of ERalpha in the male vasculature in this setting has not been explored. In conditions of overnutrition and insulin resistance, augmented arterial stiffness, endothelial dysfunction, and arterial remodeling contribute to the development of cardiovascular disease. Here, we used a rodent model of decreased ERalpha expression in ECs [endothelial cell estrogen receptor-alpha knockout (EC-ERalphaKO)] to test the hypothesis that, similar to our findings in females, loss of ERalpha signaling in the endothelium of insulin-resistant males would result in decreased arterial stiffness. EC-ERalphaKO male mice and same-sex littermates were fed a WD (high in fructose and fat) for 20 weeks and then assessed for vascular function and stiffness. EC-ERalphaKO mice were heavier than littermates but exhibited decreased vascular stiffness without differences in endothelial-dependent vasodilatory responses. Mesenteric arteries from EC-ERalphaKO mice had significantly increased diameters, wall cross-sectional areas, and mean wall thicknesses, indicative of outward hypertrophic remodeling. This remodeling paralleled an increased vessel wall content of collagen and elastin, inhibition of matrix metalloproteinase activation and a decrease of the incremental modulus of elasticity. In addition, internal elastic lamina fenestrae were more abundant in the EC-ERalphaKO mice. In conclusion, loss of endothelial ERalpha reduces vascular stiffness in male mice fed a WD with an associated outward hypertrophic remodeling of resistance arteries. |
