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Altered FOXO1 activation in the programming of cardiovascular alterations by maternal diabetes
Daniel Musikant1, Hugo Sato2, Evangelina Capobianco2
1Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
Abstract:
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.
Insights
Maternal diabetes leads to heart problems in offspring by altering extracellular matrix remodeling, involving the FOXO1 pathway. This programming affects adult cardiovascular health through specific molecular changes.
Area of Science:
- Cardiovascular Science
- Developmental Biology
- Molecular Endocrinology
Background:
- Maternal diabetes is known to cause cardiovascular changes in adult offspring.
- The underlying molecular mechanisms, particularly related to extracellular matrix remodeling, are not fully understood.
Purpose of the Study:
- To investigate if maternal diabetes programs cardiac alterations in adult offspring.
- To elucidate the role of forkhead box transcription factor 1 (FOXO1) in mediating these cardiac changes.
Main Methods:
- Evaluation of cardiac tissue from adult offspring of control and streptozotocin-induced diabetic rats.
- Analysis of glycemia, triglyceridemia, insulinemia, and markers of cardiomyopathy.
- Assessment of active FOXO1, mRNA levels of target genes (Mmp-2, Ctgf), collagen deposition, and connexin43 levels in the heart.
Main Results:
- Offspring from diabetic mothers exhibited increased glycemia, triglyceridemia, and insulinemia, along with cardiomyopathy markers.
- Elevated active FOXO1 and its target genes (Mmp-2, Ctgf) were observed in the hearts of offspring from diabetic rats.
- Increased collagen deposition and decreased connexin43 levels were noted in the hearts of offspring from diabetic mothers.
Conclusions:
- Maternal diabetes programs cardiac alterations in adult offspring.
- FOXO1 activation plays a significant role in the cardiac extracellular matrix remodeling induced by intrauterine exposure to maternal diabetes.
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