Cardiovascular Development Research

The human heart is the first functional fetal organ and undergoes several stages of development before birth. However, the underlying biology that dictates proper heart development remains poorly understood.

Investigators at Nationwide Children’s Hospital are focused on understanding the molecular pathways that regulate normal and abnormal heart development. Using mouse models, they are studying heart disease at the molecular level in order to identify essential cardiac regulators of heart development. They are also interested in understanding how genetic mutations disrupt normal cardiac development. These studies could help develop new ways to prevent, diagnose and care for congenital heart disease.

Cardiovascular Development Research Faculty

Vidu Garg, MD
Brenda Lilly, PhD
Joy Lincoln, PhD

Learn about the Center for Cardiovascular and Pulmonary Research at The Research Institute at Nationwide Children’s Hospital

Latest Findings in Cardiovascular Development Research

Inhibitory Role of Notch1 in Calcific Aortic Valve Disease

Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease.  This study discusses how loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

Access an abstract of this study: Inhibitory role of notch1 in calcific aortic valve disease. PLoS One. 2011;6(11):e27743.

How Endothelial Cells Can Control Neighboring Cells and What it May Mean for Heart Formation

Endothelial and mural cell interactions are vitally important for proper formation and function of blood vessels. This study reveals a new mechanism in which endothelial cells control neighboring mural cells through the downregulation of APOD, which, in turn, influences mural cell function by modulating adhesion.

Access an abstract of this study: Endothelial cells downregulate apolipoprotein D expression in mural cells through paracrine secretion and Notch signaling. Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H784-93. 

New Ways the Transcription Factor Snai1 May Play A Role in Cardiac Valve Development

Cardiac valves originate from endocardial cushions.  Findings from this study reveal previously unappreciated mechanisms of Snai1 for the direct regulation of matrix metalloproteinase (MMP) during endocardial cushions development.

Access an abstract of this study: Mmp15 is a direct target of Snai1 during endothelial to mesenchymal transformation and endocardial cushion development. Dev Biol. 2011 Sep 5. [Epub ahead of print]