Student Award in support of Kelly Wun, for "Modulation of Neointimal Hyperplasia after Arterial Injury by Microbe-Derived Propionate"

Annually, 3 million Americans undergo balloon angioplasty/stenting or arterial bypass for severe atherosclerosis, but rate of treatment failure by restenosis is as high as 70% at 2 years. Restenosis is caused by neointimal hyperplasia, a cellular proliferative process initiated and potentiated by inflammation. Short chain fatty acids (SCFA), products of bacterial fermentation of dietary fiber, have known anti-inflammatory and anti-proliferative effects. Butyrate, propionate, and acetate comprise over 80% of gut-derived SCFA. My project will investigate the effect of propionate on neointimal hyperplasia development. First, I will treat wild-type mice in four different ways prior to performing femoral artery wire injury: control drinking water, vancomycin-treated water, propionate-treated water, and vancomycin+propionate-treated water. I will examine neointimal hyperplasia development, perform serum analysis, and microbiome analysis of stool pellets in each group. I will analyze gene and protein expression of vascular smooth muscle cells treated with and without propionate to better understand propionate’s mechanistic effect on these cells. Specific methods will be: 1. Mouse femoral artery wire injury model of neointimal hyperplasia 2. Genomic DNA purification of fecal samples 3. 16S sequencing and analysis of fecal microbial taxonomy and diversity 4. GC-MS of serum and stool for SCFA 5. Histological analysis of mouse femoral arteries 6. Protein and RNA isolation from mouse aortic vascular smooth muscle cells 7. qRT-PCR 8. Western blotting and immunoprecipitation