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

AIDS Res Hum Retroviruses. 2001 Oct 10;17(15):1423-33. doi: 10.1089/088922201753197097.


HIV-1 cardiomyopathy has become a major cause of death in AIDS patients, but its pathogenesis is unclear. We used an antigen retrieval technique and immunostaining to investigate the hearts of 15 AIDS patients, of whom 3 had dilated cardiomyopathy. Immunocytochemistry shows infiltration of the left ventricular myocardium with mononuclear cells, ranging from minimal to diagnostic of myocarditis. The infiltrates include macrophages and CD3(+) and CD8(+) T cells. The tight junction protein ZO-1 is disrupted at the site of monocyte-macrophage vascular penetration and the coronary vessels show fibrinogen leakage in the hearts of AIDS patients, but not in the normal heart. A subset of infiltrating macrophages is doubly positive for cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase. HIV-1 peptides gp120 and Nef are expressed in macrophages and T cells, but not in cardiomyocytes. COX-2 is expressed by both gp120-positive and gp120-negative macrophages. The hearts of AIDS patients separate into those showing minimal infiltrates with low COX-2 expression and those with dense infiltrates and high COX-2; all failing hearts are in the latter group. These data suggest that COX-2-activated and HIV-1-infected monocyte-macrophages and T cells play a crucial role in the progression of HIV-1 myocarditis to HIV-1 cardiomyopathy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain / immunology
  • Coronary Vessels / immunology
  • Cyclooxygenase 2
  • HIV Infections / complications
  • HIV Infections / enzymology*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Isoenzymes / metabolism
  • Isoenzymes / physiology*
  • Kidney / immunology
  • Leukocytes / immunology
  • Liver / immunology
  • Lymphocyte Activation / immunology*
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Macrophages / virology
  • Membrane Proteins
  • Myocarditis / complications
  • Myocarditis / enzymology
  • Myocarditis / immunology*
  • Myocarditis / virology
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Prostaglandin-Endoperoxide Synthases / physiology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Ventricular Dysfunction, Left / complications
  • Ventricular Dysfunction, Left / enzymology
  • Ventricular Dysfunction, Left / immunology*
  • Ventricular Dysfunction, Left / virology


  • Isoenzymes
  • Membrane Proteins
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases