Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates
| Autor: | Alan L. Landay, Cara C. Wilson, Dongzhu Ma, Ivona Pandrea, Elaine Cornell, Anita M. Trichel, Cristian Apetrei, Jan Kristoff, Russell P. Tracy, Cuiling Xu, George S. Haret-Richter, Ruy M. Ribeiro |
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| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Primates Time Factors Cercocebus animal diseases Immunology Plenary Paper Simian Acquired Immunodeficiency Syndrome Antigens Differentiation Myelomonocytic Receptors Cell Surface Inflammation Disease Biology Thrombophilia medicine.disease_cause Biochemistry Antithrombins Fibrin Fibrinogen Degradation Products Thrombin Antigen Antigens CD Chlorocebus aethiops medicine Animals Blood Coagulation virus diseases Cell Biology Hematology Simian immunodeficiency virus medicine.disease Virology Solubility Cardiovascular Diseases Chronic Disease Disease Progression Macaca Biomarker (medicine) Simian Immunodeficiency Virus medicine.symptom Viral load Biomarkers medicine.drug |
| Zdroj: | Blood. 120:1357-1366 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2012-03-414706 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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