VEGF and RANKL regulation of NFATc1 in heart valve development.

ABSTRACT:

Rationale

NFATc1 (nuclear factor of activated T-cells cytoplasmic 1) activity in endocardial cushion (ECC) endothelial cells is required for normal ECC growth and extracellular matrix (ECM) remodeling during heart valve development.

Objective

The mechanisms of NFATc1 activation and downstream effects on cell proliferation and ECM-remodeling enzyme gene expression were examined in NFATc1 mutant mice and chick ECC explants.

Methods and results

NFATc1(-/-) mice display reduced proliferation of ECC endothelial and mesenchymal cells at embryonic day 10.5, whereas myocardial cells are unaffected. Vascular endothelial growth factor A (VEGF) activates NFATc1 and promotes ECC cell proliferation via the regulatory phosphatase, calcineurin, and mitogen-activated protein kinase-e

SUBMITTER: Combs MD 

PROVIDER: S-EPMC2749238 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature