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

Area of Science:

• Cardiovascular Research
• Developmental Biology
• Endocrinology

Background:

• Gestational diabetes mellitus (GDM) is linked to fetal congenital heart defects, specifically hypertrophic cardiomyopathy (HCM).
• Understanding the postnatal progression of cardiac changes in offspring exposed to GDM is crucial for identifying long-term risks.

Purpose of the Study:

• To investigate the effects and underlying mechanisms of postnatal cardiac remodeling in rat pups born to mothers with streptozotocin-induced gestational diabetes (GD).
• To analyze the temporal changes in cardiac structure, gene expression, and extracellular matrix remodeling.

Main Methods:

• Histological analysis and collagen expression evaluation in rat pup hearts at various postnatal ages (newborn to 35 days).
• Assessment of matrix metalloproteinase-9 (MMP-9) activity using in-gel gelatin zymography.
• Quantification of adrenergic receptors (α2AR, β3AR), myosins (Myc6, Myc7), Bcl-2, and Bax mRNA via qRT-PCR.

Main Results:

• Fetal left ventricular hypertrophy persisted until postnatal day 8 but subsequently reversed, with ventricular wall thinning observed, resembling dilated cardiomyopathy (DCM).
• Ventricular remodeling correlated with altered expression of β3 adrenergic receptors and specific microRNAs (miR-21, miR-23b).
• Increased interstitial space, altered collagen types (Col2, Col3), elevated MMP-9, and Cx43 expression indicated active extracellular remodeling.

Conclusions:

• Postnatal cardiac changes in offspring of diabetic mothers involve a transition from initial hypertrophy to wall thinning and extracellular matrix remodeling.
• These adaptations suggest a complex interplay of molecular signaling pathways, including adrenergic receptors and microRNAs, contributing to altered cardiac structure and function.
• The findings highlight the potential for long-term cardiovascular consequences in offspring exposed to GDM, necessitating further investigation into preventative and therapeutic strategies.