Rosiglitazone reverses cardiac adverse remodeling (fibrosis and vascularization) in perinatal low protein rat offspring.

Rosiglitazone, a PPAR gamma agonist, is an antidiabetic drug that shows secondary beneficial actions on cardiovascular system. Our study is centered on myocardial remodeling in maternal protein restriction offspring, focusing on fibrosis and vascularization. Wistar rat dams received one of the two diets: normal (19% protein; NP) or low protein (5% protein; LP) during gestation and lactation. Three-month-old male offspring were divided into four groups: NP treated with rosiglitazone (NPR, 5 mg/kg/day); untreated NP (NP); LP treated (LPR); untreated LP (LP) until six months. Blood pressure (BP) was higher in LP, but rosiglitazone reduced BP at the first week of treatment in LPR. Rosiglitazone had beneficial effects on fibrosis (less than 23%, P<0.05) and vascularization (plus 57% of capillary/cardiomyocyte ratio, P<0.01) compared with LP offspring, independently of blood glucose. Multivariate analysis classified 95% of groups, and LPR offspring showed values close to those of NP offspring. Rosiglitazone showed beneficial effects on rat offspring programmed by low protein diet during gestation decreasing cardiac fibrosis and enhancing myocardial vascularization. These results are significant in translational medicine for patients with chronic diseases in adult life and increased cardiovascular risk.