J. O’Connell, T. Allen, M. Carlos, K. Nisbet, P.L. Crosswhite

Gonzaga University, Spokane, WA

Chromatin remodeling complexes (CRCs) are nuclear enzymes that regulate gene accessibility and are critical for the proper development of blood vessels during gestation. Little is known about the activity CRCs in the adult cardiovascular system but preliminary studies suggest they may be important in maintaining adult cardiomyocyte and endothelial profiles. PURPOSE: To determine expressional changes of three CRCs, Brm, Brg1, and Chd4, in a high fat diet adult mouse model. METHODS: Seven male mice were evenly distributed into low fat diet (LFD) (10% fat) and HFD (60% fat) conditions and euthanized at 26-27 weeks. Tissue samples were incubated in digestion buffer to liberate RNA, which was then converted to cDNA using reverse transcriptase. RT-qPCR with mouse-specific primers was used to determine relative CRC expression compared to the housekeeping genes GAPDH and Actin. RESULTS: In kidneys from HFD animals, Brg1 was significantly upregulated when compared to the housekeeping genes Actin (t(5) = 1.53, p = 0.03) and GAPDH (t(5) = 3.05, p = 0.04) individually. While Brm also appeared to be upregulated in kidneys from HFD animals, these results were not significant. CHD4 was significantly downregulated when compared to the housekeeping gene GAPDH (t(5) = 0.31, p = 0.03). Results from heart tissue were inconclusive. CONCLUSION: Very little is known regarding the various CRCs and their ability to regulate gene expression in the adult cardiovascular system. This study is the first to study the expression of three CRCs in a HFD mouse model and preliminary evidence indicates that their activity is altered by a diet high in fat. Future studies should assess the activity of CRCs in a cell specific manner, including cardiomyocytes or endothelial cells from LFD and HFD specimens.

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