Submission Number: LIS-4-15-18

Abstract Number: 485

ESTROGEN AND PREGNANCY INCREASE CARDIAC AND CORONARY ARTERY LEVELS OF BASIC FIBROBALST GROWTH FACTOR (BFGF) AND THE FGF RECEPTOR-1.

ML Modrick ¹, Jing Zheng ¹ and Ronald R Magness* ^1,2

Perinatal Res. Labs, Dept. Ob/ Gyn, University of Wisconsin, Madison, WI ¹
Ani Sci, University of Wisconsin, Madison, WI ²

Abstract:
Estradiol-17 (E₂) and bFGF enhance endothelium-dependent coronary artery dilation and coronary perfusion. E₂ and Pregnancy increase cardiac output, enlarge left ventricular chamber volume, and decrease systemic vascular resistance. Cardiac microvascular disease increases in women after menopause, but is attenuated with estrogen therapy and can be alleviated by local cardiac FGF administration. Molecular mechanisms underlying these improved coronary effects of estrogen and pregnancy may involve endogenous bFGF or its receptor. Hypothesis: E₂ treatment and Pregnancy will increase coronary artery expression of bFGF and FGFR-1. Methods: Nonpregnant ovariectomized (OVX) ewes were treated with i.v. E₂ (5 g/kg then 6 g/kg/d; n=16) or Veh (10% EtOH; n=8) and cardiac tissues were obtained on days 0, 3,6, 8, and 10 for immunohistochemistry (IHC) analysis of bFGF and FGFR-1. Additional coronary artery cross-sections were obtained from intact Nonpregnant (NP; Luteal; n=8 /Follicular; n=6), and Pregnant (P; n=6, 120-130 days' gestation) ewes. Results: IHC staining of bFGF and FGFR-1 was observed in coronary artery endothelium, vascular smooth muscle (VSM), endocardium, and myocardium. OVX decreased bFGF and FGFR-1 staining in all tissues vs intact NP controls (Luteal = Follicular). E₂ progressively increased bFGF and FGFR-1 staining in all tissues vs OVX Veh controls (Day 0 & Veh<3<6<8=10 days of E₂). Pregnancy increased bFGF and FGFR-1 staining in coronary artery endothelium, VSM, endocardium, and myocardium; coronary artery staining P >> NP (Luteal=Follicular) = OVX E₂ > OVX Veh. Conclusion: E₂ and Pregnancy increase coronary artery endothelial, VSM, endocardial, and myocardial bFGF and FGFR-1 protein. Thus elevation of endogenous bFGF and FGFR-1 expression during estrogen therapy and pregnancy may modulate improved cardiac function and/or increases in coronary blood flow observed during these physiologic states. Support: NIH HL49210, HD33255, HL57653. .

Keywords: bFGF, FGFR1, Estrogen, Pregnancy

This abstract is being presented at: 8:00 AM in session:
Growth Factors II