Abstract 17502: Mechanical Stimulus is Coupled to Aberrant Angiogenesis in Pulmonary Artery Smooth Muscle Cells Following Superior Cavopulmonary Connection
Background: The Glenn shunt, or superior cavopulmonary connection (SCPC), connects the superior vena cava to either the right pulmonary artery (RPA) or both pulmonary arteries as a means to reduce hemodynamic load on a congenital single ventricle. However, the longevity of the SCPC is adversely affected by the formation of the pulmonary arteriovenous malformations (PAVMs), a form of aberrant angiogenesis. With SCPC, pulsatile blood flow to the RPA is replaced by nonpulsatile flow from the SVC, and the smooth muscle cells within the pulmonary artery (PASMC) lose mechanical input, which may signal a need for angiogenesis. This study tested the hypothesis that mechanical stimulus is coupled to angiogenic signaling in PASMCs in the context of SCPC.
Methods/Results: PAVM formation in the right lung was confirmed by echocardiography 6 to 8 weeks following creation of an unidirectional SCPC in pigs (n=5). PASMCs were isolated from the RPA of SCPC pigs (n=3) and referent controls (n=4) using an outgrowth method with SMC-specific Growth Medium (Promocell). AGPT1 expression was measured using PCR and normalized to heat shock binding protein-1. The angiogenic potential of AGPT1 was confirmed using a HUVEC tube formation assay following AGPT1 treatment in vitro. AGPT1 mRNA expression was increased in PASMCs from the RPA of SCPC pigs (328±88%, n=3) compared to referent controls (n=4, p<0.05; set at 100%). Following periodic biaxial stretch for 24 hours (1 Hz, 11%; Flexcell 5000), AGPT1 mRNA expression in PASMCs from the RPA of SCPC pigs, was reduced compared to unstretched PASMCs and reference control PASMCs (Figure ).
Conclusions: These results, for the first time, demonstrate that pulsatile stretch of PASMCs with SCPC decreases expression of AGP-1 mRNA, implying that loss of mechanical stretch contributes to - at least in part - to angiogenic PAVM formation with SCPC.
- © 2013 by American Heart Association, Inc.