Abstract 13221: Human Leukocyte Antigen-g Inhibits Human Coronary Artery Smooth Muscle Cell Proliferation
Background: Heart transplantation is currently the accepted therapy for patients with end-stage heart failure. However, long-term survival is limited by morbidity due to cardiac allograft vasculopathy (CAV). Human leukocyte antigen-G (HLA-G), a non-classical MHC I protein with restricted tissue expression, plays an essential role in immune tolerance and has been inversely associated with acute cellular rejection and cardiac allograft vasculopathy after heart transplantation. The proliferation of human coronary artery smooth muscle cells (HCASMC) within the intimal layer of the blood vessel might represent the most critical cellular event associated with CAV. The concentric intimal thickening with narrowing of the vessel lume leads to obstructive lesions. Our objective was to evaluate for the first time the antiproliferative properties of the HLA-G molecule on HCASMC.
Methods: Cultured primary HCASMC (n=8) were exposed to recombinant human HLA-G at various concentrations (100-1000 ng/ml). Proliferation was measured at various time points (24-120 hours) post-treatment by automated cell counting.
Results: After 24 hours of treatment there was no significant difference in proliferation between groups. At 48 hours post-treatment the proliferation of cells treated with HLA-G at 1000ng/ml was significantly lower (p=.017) than that of the untreated, control group. Similarly, at 120 hours post-treatment, the cells treated with 1000ng/ml of HLA-G displayed significantly lower (p=.043) proliferation than the controls. The viability of the cells was similar at all time-points.
Conclusion: We have shown for the first time that HLA-G inhibits HCASMC proliferation in an in vitro setting. The use of HLA-G in reducing smooth muscle cell proliferation within the coronary artery may represent a promising and novel therapeutic strategy to protect against allograft vasculopathy following heart transplantation.
- © 2012 by American Heart Association, Inc.