Nutrient Restriction In Utero Induces Remodeling of the Vascular Extracellular Matrix in Rat Offspring

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Abstract
The uterine environment may influence the development of chronic diseases later in life. The authors hypothesized that maternal nutritional restriction prenatally induces remodeling of offspring blood vessels such that they become stiff and contribute to the development of adult hypertension. To test this hypothesis, the authors studied the blood vessels of offspring of dams that were exposed to 50% maternal food restriction (MFR) from e10 to term as compared to age-matched controls. In aortas of MFR offspring, there was a significant increase in elastin and glycosaminoglycans (GAG) at 1 day of age. By 2 months of life, there was a significant increase in collagen and a decrease in GAG in MFR offspring aortas. A redistribution of elastin was also noted in MFR offspring, with a significant decrease in the interelastin laminae at both 1 day and 2 months. In mesenteric arterioles of MFR offspring, there was a decrease in GAG in 1-day-old and 2-month-old MFR offspring. There were no changes in elastin in both age groups in mesenteric arterioles, and by 2 months of life, collagen deposition was also found in these resistance vessels. There was a significant increase in expression of matrix metalloproteinase 9 (MMP-9) mRNA in 1-day-old MFR aortas, while both MMP-9 and MMP-2 expression was increased in the 4-month-old MFR aortas. These results indicate a significant remodeling of the extracellular matrix occurs in both conduit and resistance vessels. By 2 months of life, the compositions of both vessel types are consistent with stiff vessels, a contributing factor to hypertension.