The aortic expression pattern of mechanosensitive stem cell genes is spatially deranged by western-type diet but can be regulated with colchicine-based anti-inflammatory treatment

Abstract Background Inflammatory dysregulation of mechanosensitive stem cell genes may be central to atherogenesis. Purpose In the present animal model, we utilized colchicine-based regimens curtail development thoracic and abdominal aortic atheromatosis. We also explored effect anti-inflammatory therapy on atheroprotective (Klotho, HOXA5, NOTCH1, OCT4) proatherogenic (HIF1a, SOX2, BMP4, NANOG) genes. Methods Twenty-eight New Zealand White rabbits were divided four groups. The control group (n=6) was fed standard chow, A chow enriched with 1% w/w cholesterol, B (n=8) same cholesterol-enriched diet plus 2 mg/kg body weight/day colchicine 250 fenofibrate, while C 15 N-acetylcysteine (NAC). After seven weeks, all animals euthanized, their aortas resected. Atherosclerotic plaque area estimated via morphometric analysis. Gene expression quantified qRT-PCR. Results Group developed significantly more extensive atherosclerosis compared groups (p<0.001) (p<0.001). Combining NAC instead fibrate resulted in stronger atheroprotection both (MD: 6.6, 95% CI: 0.9–12.3) aorta 11.1, 6.0–16.3). aortas, Klotho downregulated controls 8.79, 1.82–15.76). Both upregulated back baseline levels Colchicine/fenofibrate NOTCH1 −4.29, −8.09 −0.48). Colchicine/NAC reduced NANOG hyperlipidemic alone 4.33, 0.37–8.29). aorta, significant downregulation HOXA5 1.39, 0.03–2.74) which reversed colchicine/NAC 0.16, −1.19 1.51). On other hand, colchicine/fenofibrate HIF1a 3.64, 0.83–6.44). No statistically differences noted terms OCT4 specimens. Conclusions pattern is spatially influenced by western-type can modified using regimens. our experiment, drove atheromatosis downregulating respectively. curtailed upregulating Klotho. combining fenofibrate increased addition NANOG. HIF1a, whereas HOXA5. Funding Acknowledgement Type funding sources: Foundation. Main source(s): This research funded Hellenic Surgical Society Atherosclerosis Society.