Premium
HIV GP120 Mediates Negative Inotropic Effect through CXCR4 Receptor on Cardiac Myocytes
Author(s) -
Yuan Youxi,
Kan Hong,
Fang Qiujuan,
Chen Fangping,
Xie Sherry,
Beto Robert J.,
Warden Bradford E,
Jain Abnash C.,
Finkel Mitchell
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.970.48
Subject(s) - inotrope , cardiac myocyte , myocyte , receptor , medicine , heart failure , microbiology and biotechnology , biology , endocrinology , pharmacology
The prognosis for patients with human immunodeficiency virus (HIV) infection has improved remarkably as a result of effective antiretroviral therapy. This has resulted in an increased awareness of cardiac complications from HIV infection, including cardiomyopathy and overt heart failure. However, the mechanisms responsible for HIV cardiomyopathy and heart failure are unknown. We have previously reported that the HIV gp120, has a p38 MAP kinase dependent negative inotropic effect on adult rat ventricular myocytes (ARVM). This signaling pathway presumably results from the binding of gp120 to a specific receptor on the surface of cardiac myocytes. HIV gp120 has been shown to bind to CD4, CXCR4 and CCR5 receptors on lymphocytes and macrophages. Accordingly, we sought to determine if HIV gp120 regulated its negative inotropic effect through activation of one of these binding sites on cardiac myocytes. AMD3100, a highly selective CXCR4 receptor antagonist, reversed HIV gp120 induced negative inotropic effect on ARVM. AMD3100 also blocked HIV gp120 phosphorylation of both p38 MAP kinase and Troponin I. The binding of gp120 to the CXCR4 receptor on ARVM was confirmed by co‐immunoprecipitation. We conclude that the negative inotropic effect of HIV gp120 is mediated by a novel signaling pathway that begins with binding to a cardiac myocyte CXCR4 receptor, followed by phosphorylation of both p38 MAP kinase and Troponin I.