Document Detail


Bacterial lipopolysaccharide enhances cardiac dysfunction but not retroviral replication in murine AIDS: roles of macrophage infiltration and toll-like receptor 4 expression.
MedLine Citation:
PMID:  16507888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cardiovascular disease is an important complication of human immunodeficiency virus/acquired immune deficiency syndrome (AIDS), but the mechanism(s) involved are poorly understood. Although co-infecting pathogens have been implicated as an important factor in AIDS progression, no studies have investigated these interactions in cardiac tissue. We recently demonstrated that the murine AIDS model (LPBM5 retroviral infection) mimics human immunodeficiency virus-related cardiac dysfunction and pathology. We tested the hypothesis that subseptic lipopolysaccharide exposure (LPS) would enhance LPBM5 progression and exacerbate cardiovascular dysfunction during murine AIDS development. LPS (5 mg/kg, Escherichia coli 0111:B4) was administered at 1, 6, and 8 weeks during LPBM5 infection, and cardiac performance was evaluated at 10 weeks using noninvasive echocardiography. LPS alone had no significant effects, whereas it amplified abnormalities in cardiac structure and function observed in murine AIDS. Cardiac dysfunction was associated with selective increases in nonfocal infiltration of CD68(+) cells and correlated with the extent of cardiac dysfunction. Retroviral progression and cardiac retroviral content remained unaltered, but cardiac toll-like receptor 4 was increased in retrovirus + LPS. We provide first-time evidence of multipathogen enhancements to retrovirus-related cardiac complications and implicate innate immune responses, not co-pathogen-induced retroviral replication, as the primary mechanism in this setting.
Authors:
Alysia A Chaves; Reshma S Baliga; Michael J Mihm; Brandon L Schanbacher; Anupam Basuray; Cynthia Liu; Angela C Cook; Leona W Ayers; John Anthony Bauer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The American journal of pathology     Volume:  168     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-01     Completed Date:  2006-04-19     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  727-35     Citation Subset:  AIM; IM    
Affiliation:
Center for Cardiovascular Medicine, Columbus Children's Research Institute, 700 Children's Dr., Columbus, OH 43205, USA.
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MeSH Terms
Descriptor/Qualifier:
Acquired Immunodeficiency Syndrome / complications*,  virology
Animals
Antigens, CD / analysis
Antigens, Differentiation, Myelomonocytic / analysis
Cardiomyopathies / immunology*,  pathology,  physiopathology
Disease Models, Animal
Heart / physiopathology
Immunohistochemistry
Leukocytes / immunology
Lipopolysaccharides / toxicity*
Macrophages / immunology*
Mice
Myocardium / chemistry,  pathology
Retroviridae / physiology
Toll-Like Receptor 4 / analysis,  genetics,  metabolism*
Virus Replication / drug effects
Grant Support
ID/Acronym/Agency:
HL-59791/HL/NHLBI NIH HHS; HL-63067/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Differentiation, Myelomonocytic; 0/CD68 protein, mouse; 0/Lipopolysaccharides; 0/Toll-Like Receptor 4
Comments/Corrections

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