Abnormalities in metalloproteinase pathways and IGF-I axis: a link between birth weight, hypertension, and vascular damage in childhood.
BACKGROUND
Although numerous studies suggest an inverse relationship between birth weight and cardiovascular disease, the mechanistic basis of this phenomenon is not fully understood. Here, we postulate that alterations in plasma concentration of matrix metalloproteinases (MMPs) and growth factors might show different associations between birth weight, blood pressure levels, and vascular function.


METHODS
Concentrations of MMP-2 and its tissue inhibitor 2 (TIMP-2), MMP-9, and insulin-like growth factor-I (IGF-I) and its binding protein IGFBP-3 were measured in 64 children (34 boys, 30 girls).


RESULTS
Small-for-gestational-age children exhibited elevated amounts of MMP-2, MMP-9, MMP-2/TIMP-2 ratio, MMP-9/TIMP-2 ratio, as well as lower concentration of IGF-I (P < 0.01), a known regulator of elastin synthesis. Similar findings were observed after adjustment for current age, gender, and race. The changes in the circulating levels of MMP-2, MMP-9, and IGF-I correlated significantly with birth weight, systolic blood pressure, and vascular function. Stepwise regression analysis demonstrated that MMP-2 was found to be an independent predictor of systolic blood pressure (R(2) = 0.08), whereas MMP-9 and birth weight were independent predictors of vascular dysfunction (R(2) = 0.38).


CONCLUSIONS
It is possible that the association of fetal programming with elevated risk for vascular and metabolic disease in later life is, at least in part, mediated by perturbations in the MMP pathways.
Sesso
Ricardo
R
Division of Nephrology, School of Medicine, Federal University of São Paulo, São Paulo, Brazil.
Franco
Maria C P
MC
D000293:Adolescent; D001724:Birth Weight; D001794:Blood Pressure; D001916:Brachial Artery / Q000503:physiopathology; D002648:Child; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D047109:Fetal Development; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D012039:Regional Blood Flow; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D014652:Vascular Diseases / Q000209:etiology* / Q000503:physiopathology; D014664:Vasodilation
D018972:Insulin-Like Growth Factor Binding Protein 3; D019716:Tissue Inhibitor of Metalloproteinase-2; D007334:Insulin-Like Growth Factor I; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9