Maternal undernutrition inhibits angiogenesis in the offspring: a potential mechanism of programmed hypertension.
The underlying etiology of many chronic diseases such as hypertension and diabetes has been traced to the in utero environment. Our interest has focused on determining the mechanism of programmed hypertension. In our rodent model of 50% maternal food restriction (MFR) from day 10 of gestation to term, the offspring develop hypertension as adults. We hypothesized that maternal undernutrition inhibits angiogenesis such that the neonate is endowed with fewer microvessels, increasing their susceptibility to develop hypertension as adults. We found significantly reduced number of mesenteric branching and renal medullary microvessels in the 1-day-old MFR newborns. Endothelial cells from MFR offspring generated shorter neovessels in culture compared with controls. The inhibition of angiogenesis was associated with a significant decrease in VEGF protein expression in mesenteric microvessels and aortas in 1-day-old offspring. However, in adulthood there was a marked increase in VEGF expression in both vessel types. The expression of endothelial nitric oxide synthase protein was also found to be increased in both renal and mesenteric microvessels and in aortas in the 1-day-old MFR offspring. These results suggest that MFR results in inhibition of VEGF expression in microvascular and aortic endothelial cells early in life, resulting in decreased angiogenesis and increased peripheral vascular resistance, both of which may contribute to offspring hypertension.
Khorram
Omid
O
Department of Obstetrics and Gynecology, Harbor-University of California at Los Angeles Medical Center, 1000 W. Carson St., Torrance, CA 90502, USA. okhorram@obgyn.humc.edu
Khorram
Naseem
N
Momeni
Mazdak
M
Han
Guang
G
Halem
Jennifer
J
Desai
Mina
M
Ross
Michael G
MG
D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000166:cytology / Q000201:enzymology; D001160:Arterioles / Q000166:cytology / Q000201:enzymology; D001724:Birth Weight; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology; D005260:Female; D048070:Fetal Nutrition Disorders / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013152:Splanchnic Circulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014655:Vascular Resistance / Q000502:physiology
D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; D040301:Vascular Endothelial Growth Factor Receptor-2