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Absence of Endothelial ER? Results in Arterial Remodeling and Decreased Stiffness in Western Diet-Fed Male Mice.

ABSTRACT: The role of estrogen receptor-? (ER?) signaling in the vasculature of females has been described under different experimental conditions and our group recently reported that lack of endothelial cell (EC) ER? in female mice fed a Western diet (WD) results in amelioration of vascular stiffness. Conversely, the role of ER? 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 ER? expression in ECs [endothelial cell estrogen receptor-? knockout (EC-ER?KO)] to test the hypothesis that, similar to our findings in females, loss of ER? signaling in the endothelium of insulin-resistant males would result in decreased arterial stiffness. EC-ER?KO 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-ER?KO mice were heavier than littermates but exhibited decreased vascular stiffness without differences in endothelial-dependent vasodilatory responses. Mesenteric arteries from EC-ER?KO 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-ER?KO mice. In conclusion, loss of endothelial ER? reduces vascular stiffness in male mice fed a WD with an associated outward hypertrophic remodeling of resistance arteries.

SUBMITTER: Manrique-Acevedo C

PROVIDER: S-EPMC5460939 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Absence of Endothelial ERα Results in Arterial Remodeling and Decreased Stiffness in Western Diet-Fed Male Mice.

Manrique-Acevedo Camila C Ramirez-Perez Francisco I FI Padilla Jaume J Vieira-Potter Victoria J VJ Aroor Annayya R AR Barron Brady J BJ Chen Dongqing D Haertling Dominic D Declue Cory C Sowers James R JR Martinez-Lemus Luis A LA

Endocrinology 20170601 6

The role of estrogen receptor-α (ERα) signaling in the vasculature of females has been described under different experimental conditions and our group recently reported that lack of endothelial cell (EC) ERα in female mice fed a Western diet (WD) results in amelioration of vascular stiffness. Conversely, the role of ERα in the male vasculature in this setting has not been explored. In conditions of overnutrition and insulin resistance, augmented arterial stiffness, endothelial dysfunction, and a ...[more]

PMID: 28430983

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Project description:Chronic kidney disease is characterized by stiffening, thinning, dilatation, and increased circumferential wall stress of large arteries, associated with increased cardiovascular risk. Kidney transplantation (KT) reverses many pathological features of chronic kidney disease and improves life expectancy; however, longitudinal studies exploring the impact of KT on recipient large arteries are scarce.This study was designed to appraise arterial changes following KT. Carotid-femoral pulse wave velocity, carotid remodeling (circumferential wall stress and carotid internal diameter), and stiffness were measured in 161 consecutive recipients receiving either a living (n=49) or a deceased (n=112) donor allograft, at 3 and 12 months after transplantation. Mean pulse wave velocity decreased from 10.8 m/s (95% confidence interval, 10.5-11.2 m/s) (at month 3) to 10.1 m/s (95% confidence interval, 9.8-10.5 m/s) (at month 12) (P<0.001). After multivariate adjustment, pulse wave velocity reduction from month 3 to month 12 was significantly larger in the living donor allograft KT (P<0.001). Circumferential wall stress decreased, 70 kPa (95% confidence interval, 68-72 kPa) to 64 kPa (95% confidence interval, 62-67 kPa), as well as carotid internal diameter and carotid stiffness (P<0.001 for all). Reductions in circumferential wall stress, diameter, and stiffness were significantly larger in the living donor allograft KT (P<0.001). When deceased donor allograft patients were classified into standard and expanded criteria donors, changes in both pulse wave velocity and circumferential wall stress were blunted in expanded criteria donors. Changes were independent of graft function and blood pressure changes.Large-artery stiffness and maladaptive carotid artery remodeling of chronic kidney disease is partially reversed within 12 months of KT and appears unrelated to renal function. Improvements were independently associated with live organ donation. Our data suggest that expanded criteria donors may hamper vascular recovery.

Dataset Information

Absence of Endothelial ER? Results in Arterial Remodeling and Decreased Stiffness in Western Diet-Fed Male Mice.

Publications

Absence of Endothelial ERα Results in Arterial Remodeling and Decreased Stiffness in Western Diet-Fed Male Mice.

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