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Intrauterine Programming of Cardiovascular Diseases in Maternal Diabetes
Romina Higa1,2, María Laura Leonardi1,2, Alicia Jawerbaum1,2
1Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Insights
Maternal diabetes adversely programs fetal heart development, increasing offspring cardiovascular disease risk. Understanding these mechanisms can guide preventative strategies for affected pregnancies.
Area of Science:
- Cardiovascular Science
- Developmental Biology
- Endocrinology
Background:
- Maternal diabetes mellitus is a significant risk factor for congenital heart defects and adult cardiovascular disease in offspring.
- The fetal heart is particularly vulnerable to the metabolic, oxidative, and inflammatory milieu of diabetic pregnancies.
- Adverse programming during fetal development can lead to long-term cardiovascular pathology.
Purpose of the Study:
- To review the mechanisms by which maternal diabetes programs cardiovascular damage in the fetal heart.
- To synthesize findings from human and experimental studies on fetal heart programming.
- To discuss potential preventive interventions for offspring of diabetic mothers.
Main Methods:
- Comprehensive literature review of human and experimental studies.
- Analysis of research on molecular and cellular mechanisms of fetal heart damage.
- Synthesis of data on epigenetic, metabolic, oxidative, inflammatory, and signaling pathway alterations.
Main Results:
- Maternal diabetes induces metabolic, pro-oxidant, and pro-inflammatory changes in the fetal heart.
- Epigenetic modifications, altered cardiac metabolism (carbohydrate and lipid), and extracellular matrix remodeling are key mechanisms.
- Dysregulation of specific signaling pathways contributes to fetal heart damage.
Conclusions:
- Maternal diabetes initiates adverse fetal programming of the heart, increasing lifelong cardiovascular disease risk.
- Understanding these pathways is crucial for developing targeted interventions.
- Preventive strategies targeting the fetal environment may mitigate long-term cardiac consequences.
Abstract:
Maternal diabetes is a prevalent pathology that increases the risk of cardiovascular diseases in the offspring, the heart being one of the main target organs affected from the fetal stage until the adult life. Metabolic, pro-oxidant, and proinflammatory alterations in the fetal heart constitute the first steps in the adverse fetal programming of cardiovascular disease in the context of maternal diabetes. This review discusses both human and experimental studies addressing putative mechanisms involved in this fetal programming of heart damage in maternal diabetes. These include cardiac epigenetic changes, alterations in cardiac carbohydrate and lipid metabolism, damaging effects caused by a pro-oxidant and proinflammatory environment, alterations in the cardiac extracellular matrix remodeling, and specific signaling pathways. Putative actions to prevent cardiovascular impairments in the offspring of mothers with diabetes are also discussed.
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