Decreased Uterine Vascularization and Uterine Arterial Expansive Remodeling with Reduced Matrix Metalloproteinase-2 and -9 in Hypertensive Pregnancy.
Am J Physiol Heart Circ Physiol. 2019 Dec 13;:
Authors: Lin C, He H, Cui N, Ren Z, Zhu M, Khalil RA
Preeclampsia is a pregnancy-related disorder characterized by hypertension-in-pregnancy (HTN-Preg), and inadequate trophoblast invasion of the uterine wall could be initiating events. We hypothesized that HTN-Preg involves decreased uterine vascularization and arterial remodeling by MMPs, and accumulation of collagen. Blood pressure (BP) and fetal parameters were assessed in normal Preg rats and Preg rats with reduced uterine perfusion pressure (RUPP), and uterine vascularity, MMP levels and collagen deposition were measured. BP was higher, and the uterus weight, litter size, and pup weight were reduced in RUPP vs Preg rats. Uterine tissue sections showed reduced number (5.75±0.95 vs 11.50±0.87) and size (0.05±0.01 vs 0.12±0.02mm2) of uterine arterioles, and diminished intima, media and adventitia of the uterine arterial wall in RUPP vs Preg rats. Immunohistochemistry showed localization of endothelial cell marker CD31 and smooth muscle marker a-actin in uterine arterial intima and media, respectively, and confirmed reduction in number and size of uterine arterioles in RUPP vs Preg rats. The cytotrophoblast marker cytokeratin-7 showed less immunostaining and invasion of uterine spiral arterioles of RUPP vs Preg rats. Uterine arterioles showed less expansion in response to increases in intraluminal pressure in RUPP vs Preg rats. Western blots, gelatin zymography and immunohistochemistry showed decreases in MMP-2 and MMP-9 and increases in the MMP substrate collagen-IV in the uterus and uterine spiral arteries of RUPP vs Preg rats. The results decreased uterine vascularization and uterine arteriolar expansive remodeling with decreased MMP-2 and MMP-9 and increased collagen-IV could be underlying mechanisms of uteroplacental ischemia in HTN-Preg.
PMID: 31834839 [PubMed – as supplied by publisher]