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. Elaine Cornell2,
  3. Cara Wilson3,
  4. Ruy M. Ribeiro4,
  5. Dongzhu Ma1,
  6. Jan Kristoff1,
  7. Cuiling Xu1,
  8. George S. Haret-Richter1,
  9. Anita Trichel1,
  10. Cristian Apetrei1,
  11. Alan Landay5, and
  12. Russell Tracy2
  1. 1 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, United States;
  2. 2 Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VE, United States;
  3. 3 Department of Medicine, University of Colorado, Aurora, CO, United States;
  4. 4 Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, United States;
  5. 5 Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL, United States
  1. * Corresponding author; email: pandrea{at}pitt.edu
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) have been correlated with increased mortality and cardiovascular events in HIV-infected patients. We compared the incidence of cardiovascular lesions and the levels of coagulation markers DD and thrombin anti-thrombin (TAT) in pathogenic SIV infections of rhesus (RMs) and pigtailed macaques (PTMs), and in nonpathogenic SIV infection of African green monkeys (AGMs) and sooty mangabeys (SMs). Hypercoagulability and cardiovascular pathology were only observed in pathogenic SIV infections. In SIVagm-infected PTMs, 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 the mechanisms of HIV-associated cardiovascular disease. In pathogenic SIV infection, DD increased early after infection and was strongly correlated with markers of immune activation/inflammation and microbial translocation (MT) and only peripherally associated with VLs. Endotoxin administration to SIVagm-infected AGMs (which lack chronic SIV-induced MT and immune activation) resulted in significant increases of DD. Altogether, our data demonstrate that, in SIV infection, hypercoagulation and cardiovascular pathology are at least in part a consequence of excessive immune activation and MT.

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