Estrogen therapy induces collateral and microvascular remodeling

Abstract

Estrogen increases proliferation and migration of cultured endothelial cells and perfusion of ischemic hindlimbs of rabbits. We tested the hypothesis that estrogen is angiogenic and arteriogenic in the heart during progressive coronary occlusion. Ovariectomized (OVX) and 17␤-estradiol (1 mg ⅐ kg Ϫ1 ⅐ wk Ϫ1 im)-treated OVX (OVX-ES) female New Zealand White rabbits were instrumented with an ameroid occluder on a proximal coronary artery. Four weeks after implantation of an ameroid occluder, we measured myocardial perfusion with microspheres at rest and during adenosine-induced maximal vasodilation. The heart was fixed by perfusion at physiological pressure, and capillary angiogenesis and remodeling were assessed by image analysis of tissue sections in collateraldependent myocardium. Coronary conductance was higher at rest and during maximal vasodilation in collateral-dependent myocardium of OVX-ES than OVX rabbits. Estrogen treatment increased the wall-to-lumen ratio of collateral vessels while it decreased the wall-to-lumen ratio of noncollateral arteries in normal regions. In normal and collateraldependent myocardium, mean capillary diameter and capillary volume density were greater in OVX-ES rabbits. However, estrogen had no effect on capillary length density in either region of the myocardium. These data suggest that estrogen induces remodeling of the collateral vasculature and may stimulate growth of the resistance vessels, thereby providing protection during development of a gradual coronary occlusion.

Synectin/syndecan‐4 regulate coronary arteriolar growth during development

“…If a similar relationship exists in the coronary vasculature, it might explain the lower arteriolar densities in the female wild‐type mice compared to their male counterparts and why arteriolar densities are greater in the syndecan‐4 null females. We previously documented that 17‐beta‐estradiol treatment of ovariectomized rabbits with a gradually developed coronary artery stenosis improved maximal myocardial perfusion to the collateral‐dependent myocardium (Lamping et al,2003). Treatment also increased mean capillary diameter and volume density.…”

Effects of oestrogen treatment and angiotensin‐converting enzyme inhibition on the microvasculature of ovariectomized spontaneously hypertensive rats

“…This might be due to an oestrogen angiogenic effect that could be partly mediated by an enhancement of endothelial precursor cells (Strehlow et al 2003) and gene expression of vascular endothelium growth factor (Karas et al 1996). Moreover, oestrogens seem to play an important role in neovascularization by upregulating angiogenesis (Kyriakides et al 2001) and increasing capillary volume density in the myocardium (Lamping et al 2003), where ovariectomy has been described to reduce ischaemia-induced neovascularization.…”

A cellular delivery system fabricated with autologous BMSCs and collagen scaffold enhances angiogenesis and perfusion in ischemic hind limb

“…The number of patients suffering from chronic hind limb ischemia is increasing, and these patients urgently need revascularization treatment 1, 2. Angiogenesis originates from the proliferation and migration of endothelial cells and contributes to the formation of collateral circulation 3. Studies have shown that collateral circulation and angiogenesis in hind limbs can be stimulated by treatment with mesenchymal stem cells (MSCs) and some biomaterials such as collagen 4–6…”

“…1,2 Angiogenesis originates from the proliferation and migration of endothelial cells and contributes to the formation of collateral circulation. 3 Studies have shown that collateral circulation and angiogenesis in hind limbs can be stimulated by treatment with mesenchymal stem cells (MSCs) and some biomaterials such as collagen. [4][5][6] Bone marrow-derived MSCs (BMSCs) were one of the primary therapeutic cell sources.…”