Estrogen receptor beta controls meningeal microvascular network architecture: potential basis for altered hemodynamics and peripheral resistance

Abstract

Estrogen is an important regulator of vascular development and function. Many groups have studied how estrogen and its receptors (ERs) control vascular function in health and disease. However, whether estrogen controls microvascular network architecture as well is virtually unknown. Here, using software developed in-house, we analyzed architectural features of meningeal microvascular networks in ERα, ERβ, and aromatase (Ar) knockout (KO) female mice and their corresponding wild type (WT) littermates. Our results showed that all three WTs did not differ from each other with respect to average microvessel length (AMVL) per network or microvessel tortuosity (extrinsic curvature). Compared to the WT, ArKO mice exhibited a 23% reduction in AMVL (p<0.01) and a 21% increase in microvessel tortuosity (p<0.05). ERαKO animals showed a similar (22%) reduction in AMVL (p<0.01), but no change in microvessel tortuosity. In contrast, ERβKO mice showed a 42% increase (p<0.01) in AMVL and a 41% increase (p<0.01) in microvessel tortuosity compared to the WT. Previous studies demonstrated that ERβKO, but not ERαKO or ArKO, mice develop the hypertensive phenotype. We propose that ERβ-dependent changes in microvessel architecture constitute a basis for altered hemodynamic conditions and increased peripheral resistance, thus contributing to the development of hypertension in ERβKO mice.