Abstract 220: Targeting Cholesterol Efflux, Autophagy, and Inflammation to Prevent Atherosclerosis

Autor:	Brian Ritchey, Harvey Lewis, Jonathan D. Smith, Amanda J Iacano, Kailash Gulshan, Shuhui Wang Lorkowski, Jennie E. Hazen, Greg Brubaker, Heather Andro, Bani A Raheem
Rok vydání:	2018
Předmět:	chemistry.chemical_compound chemistry business.industry Cholesterol Autophagy Medicine Inflammation Efflux Pharmacology medicine.symptom Cardiology and Cardiovascular Medicine business
Zdroj:	Arteriosclerosis, Thrombosis, and Vascular Biology. 38
ISSN:	1524-4636 1079-5642
Popis:	Introduction: The NLRP3 inflammasome and Toll-like receptor signaling is activated in advanced human atherosclerotic plaques, while autophagy and reverse cholesterol transport (RCT) become dysfunctional. Simultaneous targeting of these pathways can prevent CVD. Objectives: To determine if Miltefosine can prevent atherosclerosis by inducing RCT/autophagy and dampening inflammation. Methods and results: Here, we report that Miltefosine, an anti-leishmanial drug, acts to decrease atherosclerosis in vivo, and that it induced RCT/autophagy while dampening TLR signaling and NLRP3 inflammasome activity. Miltefosine treatment of macrophages disrupted lipid rafts; ~26 % decrease vs. control via alexa647-CTB binding by flow-cytometry, (p-/- mice fed chow diet + Miltefosine vs. controls (p Conclusion: Miltefosine induced RCT and autophagy while dampening TLR signaling and NLRP3 inflammasome activity, and it decreased atherosclerosis lesion burden in mice.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::0e428e91c415c4fcf731483d3606bec0 https://doi.org/10.1161/atvb.38.suppl_1.220 Zobrazit plný text záznamu