Antiretroviral drug-induced endothelial dysfunction is improved by dual PPAR α/γ stimulation in obesity.

Antiretroviral drug-induced endothelial dysfunction is improved by dual PPARα/γ stimulation in obesity. Vascul Pharmacol. 2019 Jul 05;:106577 Authors: Kamau F, Strijdom H, Mwangi P, Blackhurst D, Imperial E, Salie R Abstract Obesity rates are rising in HIV-infected populations; however, the putative role of highly active antiretroviral therapy (HAART) in the development of endothelial and cardiovascular derangements in the presence of pre-existing overweight/obesity is unclear. Although dual peroxisome proliferator-activated receptors-alpha/gamma (PPARα/γ) stimulation mitigates HAART-induced metabolic dysfunction, vascular effects are unresolved. To investigate whether HAART induces vascular dysfunction in obesity and to explore the underlying mechanisms of PPARα/γ stimulation, male Wistar rats were placed on a high-calorie diet for 16 weeks. After 10 weeks, HAART (lopinavir/ritonavir, azidothymidine/lamivudine) with/without PPARα/γ agonist, Saroglitazar, was administered daily for six weeks. Excised thoracic aorta rings were subjected to isometric tension studies and Western blot measurements. HAART+Saroglitazar-treated obese animals recorded lower adiposity indices (4.3 ± 0.5%) vs. HAART only-treated obese rats (5.6 ± 0.3%; p < .01). Maximum acetylcholine-induced vasorelaxation (Rmax), was lower in obese+HAART group (76.10 ± 3.58%) vs. obese control (101.40 ± 4.75%; p < .01). However, R...
Source: Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Vascul Pharmacol Source Type: research