title: Maternal diabetes programs hypertension and kidney injury in offspring.
abstract: We investigated whether maternal diabetes programs the offspring to develop hypertension and kidney injury in adulthood and examined potential underlying mechanisms. In a murine model we studied the offspring of three groups of dams (non-diabetic, diabetic, and diabetic treated with insulin). Mean systolic blood pressure in the offspring was monitored from 8 to 20 weeks. Body and kidney weights in the offspring of diabetic mothers were significantly lower than in offspring of non-diabetic mothers. Offspring of diabetic mothers developed hypertension, microalbuminuria, and glucose intolerance. Increased accumulation of extracellular matrix proteins in the glomeruli and marked upregulation of angiotensinogen, angiotensin II type 1 receptor, angiotensin-converting enzyme, transforming growth factor beta-1 (TGF-beta1), and plasminogen activator inhibitor-1 (PAI-1) gene expression were evident in the renal cortex of hypertensive offspring of diabetic mothers. By contrast, angiotensin-converting enzyme-2 (ACE2) gene expression was lower in the hypertensive offspring of diabetic mothers than in that of non-diabetic mothers. These changes were prevented in the offspring of insulin-treated diabetic mothers. These data indicate that maternal diabetes induces perinatal programming of hypertension, renal injury, and glucose intolerance in the offspring and suggest a central role for the activation of the intrarenal renin-angiotensin system and TGF-beta1 gene expression in this process.
authors.affiliation: Department of Medicine, Université de Montréal and Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM)-Hôtel-Dieu, 8-227, Pavillon Masson, 3850 Saint Urbain Street, Montreal, QC, H2W 1T7, Canada.
authors.forename: Yun-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chenier
authors.forename: Stella
authors.initials: S
authors.lastname: Tran
authors.forename: Michael
authors.initials: M
authors.lastname: Scotcher
authors.forename: Shiao-Ying
authors.initials: SY
authors.lastname: Chang
authors.forename: Shao-Ling
authors.initials: SL
authors.lastname: Zhang
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018149:Glucose Intolerance / Q000235:genetics; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000254:growth & development / Q000473:pathology; D051379:Mice; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D007328:Insulin; D053773:Transforming Growth Factor beta1; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2