Essential role of HIV type 1-infected and cyclooxygenase 2-activated macrophages and T cells in HIV type 1 myocarditis.
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.
Liu
Q N
QN
Department of Medicine, West Los Angeles VA Medical Center and UCLA School of Medicine, Los Angeles, California 90095-1769, USA.
Reddy
S
S
Sayre
J W
JW
Pop
V
V
Graves
M C
MC
Fiala
M
M
D001921:Brain / Q000276:immunology; D003331:Coronary Vessels / Q000276:immunology; D051546:Cyclooxygenase 2; D015658:HIV Infections / Q000150:complications / Q000201:enzymology* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D007668:Kidney / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D008565:Membrane Proteins; D009205:Myocarditis / Q000150:complications / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000201:enzymology / Q000276:immunology* / Q000821:virology
D007527:Isoenzymes; D008565:Membrane Proteins; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases