Browning WAT inhibits atherosclerosis Browning WAT inhibits atherosclerosis Hyperlipidemia, coupled with inflammation, is integral to the atherosclerotic cardiovascular disease (ASCVD) process. Current medical therapies for ASCVD cannot correct obesity, the main cause of hyperlipidemia and chronic low-grade inflammation. Obesity leads to increased circulating levels of triglyceride-rich and cholesterol-rich lipoprotein remnant particles, recently recognized as a major contributor to the development of atherosclerosis. Abundant white adipose tissue (WAT) in humans makes browning of WAT a promising means to both slim the body and treat atherosclerosis. Current strategies for browning WAT are plagued by side effects and toxicity. We have developed resveratrol (RES) encapsulated nanoparticles (NPs) carrying adipose stromal stem cells (ASC)-targeting peptides (ASC-targeted RES-NPs). The NPs enhanced targeted delivery of RES to ASCs after intravenous administration, resulting in browning of subcutaneous WAT and subsequent weight and fat loss, but they still accumulated in the liver. In order to bypass the liver and other tissues, we will subcutane-ously deliver ASC-targeted RES-NPs to inguinal WAT in mice in this project. The objective of this proposal is to determine the inhibitory effects of browning WAT using ASC-targeted RES-NPs on atherosclerosis in APOE*3-Leiden.CETP mice, an atherosclerosis mouse model with human-like lipo-protein metabolism. We hypothesize that browning WAT can inhibit atherosclerosis development by decreasing inflammation, enhancing triglyceride and remnant cholesterol clearance from the circulation, and promoting re-verse cholesterol transport. The novelty of this research is as a pioneering study on the effects of beige adipocyte formation and activation impacts on atherosclerosis, in particular, the proposed use of ASC-targeted RES-NPs to simultaneously treat both obesity and atherosclerosis. The project addresses the following two specific aims: 1) determining the effects of browning WAT on atherosclerosis in mice; and 2) determining the underlying mechanisms of lipid and lipoprotein metabolism in mice. Browning WAT using local and targeted delivery approaches represents an innovative strategy for the treatment of atherosclerosis with enhanced efficacy and minimized side effects and toxicity. This project will strengthen research and development at Texas Tech University, and serve as fertile ground for research training of undergraduate and graduate students in the fields of nanomedicine and ASCVD.
|Effective start/end date||9/1/20 → 11/30/21|
- American Heart Association: $48,192.00
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