Stromal derived factor-1a may help form aortopulmonary collateral vessels in cyanotic congenital heart disease

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NHLBI	CLIN-16

Authors

• N. Sandeep
• Y. Mukouyama

Abstract

Cyanotic congenital heart disease patients often have abnormal aortopulmonary collateral (APC) blood vessel connections. An understanding of why APCs form, which is currently poor, would help develop anti-APC agents. We hypothesized that hypoxia-inducible angiogenic factors such as vascular endothelial growth factor (VEGF) and stromal derived factor (SDF-1a or CXCL12) may help form APCs. During cardiac catheterization, we collected blood from the femoral vein and artery in cyanotic and acyanotic children to measure plasma factor levels. To assess angiogenic potential of patient plasma, we developed a 3-D in vitro cell sprouting assay that recapitulates angiogenic sprouting, a possible key step in APC formation. The presence of APCs identified angiographically was correlated with factor levels and cell sprouting activity. Our preliminary results demonstrate a trend towards increased plasma levels of SDF-1a, VEGF-A, VEGF-C, VEGF-D, and soluble fms-like tyrosine kinase-1 (sFlt-1) in patients with APCs versus patients without APCs. Among them, increased SDF-1a levels are reflected by increased cell sprouting. This suggests that SDF-1a may play a possible and previously undescribed role in APC formation by inducing cell sprouting. Our ongoing study is the first to simultaneously correlate angiography with plasma angiogenic activity in vitro and angiogenic factor measurements in patients with APCs.

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