Blood Journal
Leading the way in experimental and clinical research in hematology

Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates

  1. Ivona Pandrea1,2,
  2. Elaine Cornell3,
  3. Cara Wilson4,
  4. Ruy M. Ribeiro5,
  5. Dongzhu Ma1,
  6. Jan Kristoff1,
  7. Cuiling Xu1,
  8. George S. Haret-Richter1,
  9. Anita Trichel1,6,
  10. Cristian Apetrei1,7,
  11. Alan Landay8, and
  12. Russell Tracy9
  1. 1Center for Vaccine Research, and
  2. 2Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA;
  3. 3Department of Pathology, University of Vermont, Burlington, VT;
  4. 4Department of Medicine, University of Colorado, Aurora, CO;
  5. 5Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM;
  6. 6Division of Laboratory Animal Resources, and
  7. 7Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA;
  8. 8Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL; and
  9. 9Department of Pathology and Biochemistry, University of Vermont, Burlington, VT
This article has an Erratum 124(6):981
This article has an Erratum 124(6):981

Abstract

HIV infection is associated with increased risk of cardiovascular complications, the underlying mechanism of which remains unclear. Plasma levels of the coagulation biomarker D-dimer (DD) correlate with increased mortality and cardiovascular events in HIV-infected patients. We compared the incidence of cardiovascular lesions and the levels of the coagulation markers DD and thrombin antithrombin in pathogenic SIV infections of rhesus and pigtailed macaques (PTMs) and in nonpathogenic SIV infection of African green monkeys (AGMs) and sooty mangabeys. Hypercoagulability and cardiovascular pathology were only observed in pathogenic SIV infections. In PTMs infected with SIV from AGMs (SIVagm), DD levels were highly indicative of AIDS progression and increased mortality and were associated with cardiovascular lesions, pointing to SIVagm-infected PTMs as an ideal animal model for the study of HIV-associated cardiovascular disease. In pathogenic SIV infection, DD increased early after infection, was strongly correlated with markers of immune activation/inflammation and microbial translocation (MT), and was only peripherally associated with viral loads. Endotoxin administration to SIVagm-infected AGMs (which lack chronic SIV-induced MT and immune activation) resulted in significant increases of DD. Our results demonstrate that hypercoagulation and cardiovascular pathology are at least in part a consequence of excessive immune activation and MT in SIV infection.

  • Submitted March 1, 2012.
  • Accepted May 22, 2012.
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