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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/28815

Title: Treatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats
Authors: Everson, Frans
Genis, Amanda
Ogundipe, Temitope
De Boever, Patrick
Goswami, Nandu
Lochner, Amanda
Blackhurst, Dee
Strijdom, Hans
Issue Date: 2018
Publisher: PUBLIC LIBRARY SCIENCE
Citation: PLOS ONE, 13(12) (Art N° e0208537)
Abstract: HIV-infection, certain antiretroviral drug classes, especially protease inhibitors (PI), and obesity are associated with increased ischaemic heart disease (IHD) risk. However, the effect of PI-free fixed dose combination (FDC) antiretroviral therapy (ART) on hearts exposed to ischaemia-reperfusion injury (I/R) is unknown, particularly in obesity. This is becoming relevant as World Health Organisation guidelines recommend a FDC ART containing (non-) nucleoside reverse transcriptase inhibitors (tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) as first-line HIV treatment. Additionally, obesity rates are rising in HIV-infected populations, not only in ART-experienced individuals, but also at the time of ART initiation, which may further increase the risk of IHD. Therefore, we investigated the effects of PI-free FDC ART in myocardial I/R-exposed hearts from obese rats. Obesity was induced in male wistar rats via a 16-week high calorie diet. At week 10, treatment with a FDC ART drug containing TDF/FTC/EFV was initiated. Biometric and metabolic parameters, as well as myocardial functional recovery and infract size (IS), and myocardial signalling proteins following I/R were assessed after 16 weeks. Obese rats presented with increased body and intraperitoneal fat mass, elevated triglyceride and TBARS levels, whilst the hearts responded to I/R with impaired functional performance and increased IS. The FDC ART treatment did not alter biometric and metabolic parameters in obese rats. In a novel finding, ART protected obese hearts against I/R as shown by improved functional performance and smaller IS vs. untreated obese hearts. Cardioprotection was underscored by increased myocardial phosphorylated endothelial nitric oxide synthase (eNOS) and reduced AMP-kinase levels. In conclusion, these results demonstrate for the first time, that 6-weeks treatment of obese rats with a FDC ART drug specifically containing TDF/FTC/EFV conferred cardioprotection against I/R. The FDC ART-induced cardioprotection was seemingly unrelated to metabolic changes, but rather due to direct cardiac mechanisms including the up-regulation of myocardial eNOS.
Notes: [Everson, Frans; Genis, Amanda; Ogundipe, Temitope; Lochner, Amanda; Strijdom, Hans] Stellenbosch Univ, Div Med Physiol, Fac Med & Hlth Sci, Cape Town, South Africa. [De Boever, Patrick] Flemish Inst Technol Res VITO, Environm Risk & Hlth, Mol, Belgium. [De Boever, Patrick] Hasselt Univ, Ctr Environm Sci, Diepenbeek, Belgium. [Goswami, Nandu] Med Univ Graz, Otto Loewi Res Ctr, Dept Physiol, Graz, Austria. [Blackhurst, Dee] Univ Cape Town, Fac Hlth Sci, Div Chem Pathol, Cape Town, South Africa.
URI: http://hdl.handle.net/1942/28815
DOI: 10.1371/journal.pone.0208537
ISI #: 000452212400105
ISSN: 1932-6203
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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