Active Foxo1 is increased in the heart of offspring from diabetic rats altered FOXO1 activation in the programming of cardiovascular alterations by maternal diabetes

SATO H; JAWERBAUM A; CAPOBIANCO E; HIGA R; MUSIKANT D; WHITE V

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2019 vol. 479 p. 78 - 86

0303-7207

Maternal diabetes programs cardiovascular alterations in the adult offspring but the mechanisms involved remain unclarified. Here, we addresed whether maternal diabetes programs cardiac alterations related to extracellular matrix remodeling in the adult offspring, as well as the role of forkhead box transcription factor 1 (FOXO1) in the induction of these alterations. The heart from adult offspring from control and streptozotocin-induced diabetic rats was evaluated. Increased glycemia, triglyceridemia and insulinemia and markers of cardiomyopathy were found in the offspring from diabetic rats. In the heart, an increase in active FOXO1 and mRNA levels of its target genes, Mmp-2 and Ctgf, genes related to an altered extracellular matrix remodeling, together with an increase in collagen deposition and a decrease in the connexin43 levels, were found in the offspring from diabetic rats. Altogether, these results suggest an important role of FOXO1 activation in the cardiac alterations induced by intrauterine programming in maternal diabetes.