Human Leukocyte Antigen-G Inhibits Human Coronary Artery Smooth Muscle Cell Proliferation

Abstract

Purpose 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 and Materials Commercially available primary HCASMC (n=8) were seeded for 24h, and then 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 At 24 and 48 hours of treatment there was no significant difference in proliferation between the groups. At 120 hours post-treatment, the proliferation of cells treated with HLA-G at 500 and 1000ng/ml was significantly lower ( * p=0.041 and * p=0.004, respectively) than that of the untreated, control group. At 120 hours there was also a significant decrease in proliferation of the cells treated with 1000ng/ml when compared to the group exposed to 100ng/ml ( * p=0.020). The viability of the cells was similar at all time-points. Conclusions 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.