Changes in miR 21 and 23b expression in postnatal hypertrophic heart derived from gestational diabetes precede dilated cardiomyopathy

Abstract

Gestational diabetes mellitus (GDM) increases the risk of fetal congenital ventricular hypertrophic cardiomyopathy (HCM). We explored the effects and mechanisms of the postnatal progression of fetal hypertrophic failure in rat pups with STZ-induced Gestational Diabetes (GD). The hearts of rat pups (newborn [NB], 8, 15, 25 and 35 days postnatal) were obtained. Histological characteristics and expression of collagen were evaluated. In-gel-gelatin zymography for MMP-9 activation was performed. Adrenergic receptors (α2AR and β3AR), myosins (Myc6 and Myc7), Bcl-2 and Bax mRNA expression were quantified by qRT-PCR. Fetal hypertrophy of the left ventricular lateral wall (LVLW) in rat pups with DG persists until day 8, although this process appears to be reversed during the postnatal stage. The temporal continuity of the study demonstrated a thinning of the ventricular wall, similar to dilated cardiomyopathy (DCM). This ventricular remodeling process is associated with the expression of β3 adrenergic receptors and miR-21, -23b. The Bax/Bcl2 ratio was significantly reduced only at early ages. In addition, the increase in interstitial space in all ages, as well as the predominance of early ages expression of Col2 and increased expression of Col3, MMP-9 and Cx43 in late ages, is the result of an active extracellular remodeling in the hearts of rat pups with GD.