HIV-Associated Cardiovascular Disease: Role of Connexin 43.

TitleHIV-Associated Cardiovascular Disease: Role of Connexin 43.
Publication TypeJournal Article
Year of Publication2017
AuthorsPrevedel, L, Morocho, C, Bennett, MVL, Eugenin, EA
JournalAm J Pathol
Volume187
Issue9
Pagination1960-1970
Date Published09/2017
ISSN1525-2191
KeywordsAdult, Aged, Aged, 80 and over, Cardiovascular Diseases, CD4 Lymphocyte Count, Connexin 43, Female, HIV Infections, Humans, Inflammation, Male, Middle Aged, Myocardium, Young Adult
Abstract

Chronic HIV infection due to effective antiretroviral treatment has resulted in a broad range of clinical complications, including accelerated heart disease. Individuals with HIV infection have a 1.5 to 2 times higher incidence of cardiovascular diseases than their uninfected counterparts; however, the underlying mechanisms are poorly understood. To explore the link between HIV infection and cardiovascular diseases, we used postmortem human heart tissues obtained from HIV-infected and control uninfected individuals to examine connexin 43 (Cx43) expression and distribution and HIV-associated inflammation. Here, we demonstrate that Cx43 is dysregulated in the hearts of HIV-infected individuals. In all HIV heart samples analyzed, there were areas where Cx43 was overexpressed and found along the lateral membrane of the cardiomyocyte and in the intercalated disks. Areas of HIV tissue with anomalous Cx43 expression and localization also showed calcium overload, sarcofilamental atrophy, and accumulation of collagen. All these changes were independent of viral replication, CD4 counts, inflammation, and type of antiretroviral treatment. Overall, we propose that HIV infection increases Cx43 expression in heart, resulting in tissue damage that likely contributes to the high rates of cardiovascular disease in HIV-infected individuals.

DOI10.1016/j.ajpath.2017.05.011
Alternate JournalAm. J. Pathol.
PubMed ID28688235
PubMed Central IDPMC5809504
Grant ListU24 MH100925 / MH / NIMH NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
R01 MH096625 / MH / NIMH NIH HHS / United States
R01 NS105584 / NS / NINDS NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States