Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates.
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.
Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA. pandrea@pitt.edu
Ivona
I
Pandrea
Elaine
E
Cornell
Cara
C
Wilson
Ruy M
RM
Ribeiro
Dongzhu
D
Ma
Jan
J
Kristoff
Cuiling
C
Xu
George S
GS
Haret-Richter
Anita
A
Trichel
Cristian
C
Apetrei
Alan
A
Landay
Russell
R
Tracy
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000991:Antithrombins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000473:pathology; D016664:Cercocebus / Q000097:blood / Q000821:virology; D002522:Chlorocebus aethiops; D002908:Chronic Disease; D018450:Disease Progression; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008251:Macaca / Q000097:blood / Q000821:virology; D011323:Primates / Q000097:blood* / Q000821:virology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000502:physiology*; D012995:Solubility / Q000187:drug effects; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000991:Antithrombins; D015415:Biomarkers; D000098902:CD163 Antigen; D005338:Fibrin Fibrinogen Degradation Products; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; C036309:fibrin fragment D; D013917:Thrombin