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Effects of everolimus and HLA‐G on cellular proliferation and neutrophil adhesion in an in vitro model of cardiac allograft vasculopathy
Author(s) -
Mociornita Amelia G.,
Adamson Mitchell B.,
Tumiati Laura C.,
Ross Heather J.,
Rao Vivek,
Delgado Diego H.
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15015
Subject(s) - everolimus , medicine , downregulation and upregulation , western blot , heart transplantation , cell adhesion , endothelial stem cell , immunology , human leukocyte antigen , transplantation , pharmacology , cell , in vitro , biology , antigen , biochemistry , gene
Human leukocyte antigen‐G (HLA‐G) expression is modulated by immunosuppressant use and is associated with lower incidence of graft rejection and cardiac allograft vasculopathy (CAV). We examined whether everolimus induces HLA‐G expression and inhibits human coronary artery smooth muscle cell (HCASMC) proliferation, a critical event in CAV. Also, we examined whether TNFα‐stimulated neutrophil adhesion is inhibited by HLA‐G on human coronary artery endothelial cells (HCAECs). HLA‐G expression in HCASMCs following everolimus treatment was determined by western‐blot densitometric analysis. HCASMCs proliferation following incubation with recombinant HLA‐G was determined by automated cell counter detecting 2‐10 µm particles. Assessment of recombinant HLA‐G on neutrophil adhesion to HCAECs in response to TNF‐α induced‐injury was determined by nonstatic adhesion assays. HLA‐G expression was upregulated in HCASMCs following everolimus exposure (1000 ng/ml; P < .05). HLA‐G (500, 1000 ng/ml; both P < .05) reduced HCASMC proliferation and inhibited TNFα‐stimulated neutrophil adhesion to endothelial cells at all concentrations (0.1‐1 ng/ml; all P < .001). Our study reveals novel regulation of HLA‐G by everolimus, by demonstrating HLA‐G upregulation and subsequent inhibition of HCASMC proliferation. HLA‐G is a potent inhibitor of neutrophil adhesion to HCAECs. Findings support HLA‐G’s importance and potential use in heart transplantation for preventative therapy or as a marker to identify patients at high risk for developing CAV.