Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates

Ivona Pandrea, Elaine Cornell, Cara Wilson, Ruy M. Ribeiro, Dongzhu Ma, Jan Kristoff, Cuiling Xu, George S. Haret-Richter, Anita Trichel, Cristian Apetrei, Alan Landay, Russell Tracy

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1357-1366
Number of pages10
JournalBlood
Volume120
Issue number7
DOIs
StatePublished - Aug 16 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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