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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
Source: 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.
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ISSN: 1932-6203
e-ISSN: 1932-6203
DOI: 10.1371/journal.pone.0208537
ISI #: 000452212400105
Rights: 2018 Everson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Category: A1
Type: Journal Contribution
Validations: ecoom 2019
Appears in Collections:Research publications

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