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Decreased Uterine Vascularization and Uterine Arteriolar Expansive Remodeling by Matrix Metalloproteinases in Hypertensive Pregnancy
Author(s) -
He Hong,
Lin Chen,
Ren Zongli,
Zhu Minglin,
Khalil Raouf A
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1212.9
Subject(s) - uterus , medicine , placentation , uterine artery , spiral artery , endocrinology , blood pressure , vascularity , internal elastic lamina , fetus , pregnancy , placenta , gestation , artery , biology , pathology , genetics
Normal pregnancy is associated with extensive remodeling of spiral arteries in order to maintain nutrients and blood supply to the growing fetus. Inadequate placentation and invasion of the uterine wall could lead to uteroplacental ischemia and hypertensive pregnancy (HTN‐Preg); however, the extent of uterine vascularization and the mechanisms involved are unclear. We hypothesized that HTN‐Preg is associated with changes in uterine vascularization and arterial remodeling by matrix metalloproteinases (MMPs). Blood pressure (BP) and fetal parameters were assessed on day‐19 in normal pregnant rats (Preg) and pregnant rats with reduced uterine perfusion pressure (RUPP), and the uteri were isolated for measurement of tissue vascularity and MMPs expression/activity. BP was greater and pups number and weight, and uterus weight were reduced in RUPP vs. Preg rats (BP 128.2±1.7 vs. 91.60±2.8mmHg; pups number 8.8±1.1 vs. 13.00±0.7; pup weight 1.48±0.059 vs. 2.02±0.02g; uterus weight 3.82±0.37 vs. 4.92±0.27g). Histological analysis of uterine tissue sections showed reduced total number and whole area of uterine arterioles in RUPP vs. Preg rats (number 5.75±0.95 vs. 11.50±0.87; area 0.05±0.01 vs. 0.12±0.02mm 2 ). Immunohistochemistry with the endothelial cell marker CD31 showed localization in the uterine arterial intima and confirmed reduction in the number and size of uterine arterioles in RUPP vs. Preg rats. Further analysis of the uterine arterial wall showed reduction in the area of all three layers of the uterine arterial wall in RUPP vs. Preg rats (intima 0.015±0.003 vs. 0.031±0.005; media 0.012±0.002 vs. 0.038±0.005; adventitia 0.021±0.003 vs. 0.048±0.007mm 2 ). Western blots and gelatin zymography showed a decrease in expression and activity of MMP‐2 and ‐9 in uterus and uterine arteries of RUPP vs. Preg rats. Immunohistochemistry showed decreased total amount of MMP‐2 and ‐9 in the uterus, and reduction in MMP distribution in the intima and media of uterine arteries of RUPP vs. Preg rats. Thus, in HTN‐Preg rats there is reduction in the number and size of uterine arteries and decreased expression and activity of MMP‐2 and ‐9. These results suggest that reduced uterine vascularization and uterine arteriolar expansive remodeling by MMPs could be a factor in the uteroplacental ischemia associated with HTN‐Preg and preeclampsia. Support or Funding Information This work was supported by grants from National Heart, Lung, and Blood Institute (HL‐65998,HL‐111775).