Maternal diabetes programs hypertension and kidney injury in offspring.
Pediatr Nephrol
; 25(7): 1319-29, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20422227
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Gravidez em Diabéticas
/
Efeitos Tardios da Exposição Pré-Natal
/
Regulação da Expressão Gênica no Desenvolvimento
/
Diabetes Mellitus Experimental
/
Nefropatias Diabéticas
/
Hipertensão
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Pediatr Nephrol
Ano de publicação:
2010
Tipo de documento:
Article