Abstract 21362: The Combination Antiretroviral Therapy (cart) Inhibits Efferocytosis-Related Gene Expression via Activating P90rsk and Accelerates Atherosclerosis
| العنوان: | Abstract 21362: The Combination Antiretroviral Therapy (cart) Inhibits Efferocytosis-Related Gene Expression via Activating P90rsk and Accelerates Atherosclerosis |
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| المؤلفون: | Nhat Tu Le, Meera V. Singh, Kyung Ae Ko, Kyung-sun Heo, Yunting Tao, Jan Medina, Tamlyn Thomas, Nicole E. Stirpe, Wang Lu, Alicia Tyrell, Kathleen J. Gates, Xing Qui, Keigi Fujiwara, Sanjay B. Maggirwar, Giovanni Schifitto, Jun-ichi Abe |
| المصدر: | Circulation. 136 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Physiology (medical), Cardiology and Cardiovascular Medicine |
| الوصف: | Background: Increased incidence of cardiovascular disease (CVD) in HIV patients has been established, but the consequence of anti-HIV therapies in CVD is unclear. The activation of p90RSK in endothelial cells is a critical event in atherosclerosis, but its role in macrophage is unknown. Hypothesis: macrophage p90RSK plays a role in anti-HIV drug-induced CVD and atherosclerosis. Methods and Results: In macrophages, efferocytosis-related signaling was upregulated and inflammatory gene expression was down-regulated in a p90RSK activity-dependent manner. Using Lysm-Cre dominant negative (DN) p90RSK transgenic mice in LDLR -/- background fed a high-cholesterol diet, we found that p90RSK activation increases plaque formation, inducing pro-atherogenic phenotypes and enhancing M1 polarization. Every cART regimen we tested, except backbone regimen, activated macrophage p90RSK, reduced efferocytosis, and increased M1-type related gene expression. In human, peripheral monocytes were isolated from HIV infected individuals on stable cART for at least 1 year and with viral load ≤50 copies/mL and also from HIV negative and non-cART treated controls matched for age, gender, environment and Reynolds CVD risk score. We found significantly increased p90RSK activation in the cART-treated group, and additional treatment of low dose of H 2 O 2 (200 nM) accelerated p90RSK activation more in the macrophage isolated from cART-treated patients than those in control patients in vitro . Conclusions: Our results demonstrate that p90RSK is robustly activated by anti-HIV drug treatments known to be a high CVD risk. This activation culminates in reduced activity of macrophage efferocytosis, thereby accelerating atherosclerotic plaque formation. Monocyte/macrophage p90RSK can be a good target and an excellent biological marker to prevent and predict drugs-induced CVD. |
| تدمد: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circ.136.suppl_1.21362 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::2e561779ac8ee0ab6fe5f81468369acc https://doi.org/10.1161/circ.136.suppl_1.21362 |
| رقم الانضمام: | edsair.doi...........2e561779ac8ee0ab6fe5f81468369acc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
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| DOI: | 10.1161/circ.136.suppl_1.21362 |