Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1

Q N Liu1, S Reddy, J W Sayre

  • 1Department of Medicine, West Los Angeles VA Medical Center and UCLA School of Medicine, Los Angeles, California 90095-1769, USA.

Insights

HIV-1 cardiomyopathy in AIDS patients involves heart muscle inflammation (myocarditis) caused by infected immune cells. Cyclooxygenase-2 (COX-2) activation in these cells is linked to disease progression.

Area of Science:

  • Immunology
  • Cardiology
  • Virology

Background:

  • HIV-1 cardiomyopathy is a significant cause of mortality in AIDS patients.
  • The precise mechanisms driving HIV-1 cardiomyopathy remain incompletely understood.

Purpose of the Study:

  • To investigate the role of immune cell infiltration and specific molecular markers in the pathogenesis of HIV-1 cardiomyopathy.
  • To explore the relationship between HIV-1 infection, inflammation, and cardiac dysfunction.

Main Methods:

  • Utilized antigen retrieval and immunostaining techniques on cardiac tissue from 15 AIDS patients (3 with dilated cardiomyopathy) and controls.
  • Performed immunocytochemistry to identify infiltrating mononuclear cells (macrophages, T cells) and assess tight junction protein (ZO-1) disruption and vascular leakage.
  • Examined the expression of HIV-1 peptides (gp120, Nef), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in cardiac cells.

Main Results:

  • Identified mononuclear cell infiltrates, including macrophages and T cells (CD3+, CD8+), in the myocardium of AIDS patients, consistent with myocarditis.
  • Observed disruption of the tight junction protein ZO-1 and fibrinogen leakage in coronary vessels of AIDS patients, indicating impaired vascular integrity.
  • Found a subset of macrophages positive for both COX-2 and iNOS. HIV-1 peptides gp120 and Nef were expressed in macrophages and T cells.
  • Correlated higher COX-2 expression and denser inflammatory infiltrates with cardiac failure in AIDS patients.

Conclusions:

  • HIV-1-infected monocyte-macrophages and T cells, particularly those with activated COX-2, play a critical role in the progression of HIV-1 myocarditis to cardiomyopathy.
  • Impaired vascular integrity and inflammatory responses mediated by these cells contribute to cardiac dysfunction in AIDS.

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