Division of Cardiovascular Diseases Strategic Plan

Goals in Cardiovascular Clinical Problems or Disease States

2.1a. Explain the developmental and genetic basis of congenital heart disease

Table of Contents

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Overview

Congenital heart defects are the most common type of birth defect, affecting about 1 in 100 newborns, and resulting in more than 35,000 babies born in the U.S. each year with congenital heart defects. Understanding the complex molecular, genetic, and environmental causes of congenital heart disease is dependent on a thorough grounding in the processes controlling normal heart development. The NHLBI has provided strong support of basic research in cardiovascular (CV) development over the last two decades. Now the challenges are to continue the current gene-by-gene approach while integrating the discoveries into a comprehensive scheme of complex signaling and regulatory pathways, and to translate current and future work first to clinical research, then ultimately to clinical practice.

Strategies to Accomplish this Goal May Entail:

Basic Research:

  • Discover genes that control cardiac development in animal models.
  • Expand our understanding of heart development signaling and regulatory pathways and components by using animal models and computational modeling.
  • Explore the role of microenvironments in the control of CV development.
  • Provide comprehensive access to phenotyping technologies and resources necessary to fully characterize animal models of normal and defective CV development.
  • Expand our understanding of cardiopulmonary interactions during development.
  • Explore in animal models, the role of nutrition and metabolic disorders in abnormal heart development (such as vitamin deficiency, inborn errors of cholesterol metabolism, or maternal obesity), and the capacity for nutritional intervention to rescue fetuses at risk.

Translational Research:

  • Discover genes that cause congenital CV malformations (CCVMs) in humans.
  • Relate signaling and regulatory pathways to human disease by using genotype-phenotype association studies of human congenital heart disease to direct basic research toward those pathways most relevant to human disease, and to use animal models and computational modeling to prioritize and validate candidate associations identified by the human studies.
  • Address the limitations of association studies in small disease populations and for polymorphisms with low allelic frequencies by exploiting the potential of bioinformatic and computational approaches through coordination with Clinical Translation Science Awards (CTSA) resources, Division of Prevention and Population Sciences (DPPS) and other NIH scientific staff, and the NIH Office of Rare Diseases.

Clinical Research:

  • Evaluate genotypic influence on clinical outcomes.
  • Explore pharmacogenomic interactions and other associations between genotype and interventional response to identify personalized approaches to treatment.
  • Clarify through epidemiologic and clinical studies how maternal diet and nutritional status influence the risk of delivering an infant with a congenital cardiac malformation, particularly among women with identified genetic polymorphisms influencing nutrient metabolism and requirements.

Contributing Sources:

September 2008

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