Chronic photoperiodic manipulation induced chronodisruption upregulates HSP60 during early pro-atherogenic remodeling in thoracic aorta of C57BL/6J mice

Abstract

Abstract Background Circadian disruption is often associated with aggravation of atherosclerosis; however, the pathophysiological mechanisms underlying atherogenic initiation in normolipidemic diet remains unclear. Most of the studies done for understanding circadian disruption induced atherosclerosis have been carried out in murine model of hyperlipidemia induced atherosclerosis. The present study investigates pro-atherogenic events in response to chronic photoperiodic manipulation induced chronodisruption (PMCD) in C57BL/6J mice fed with laboratory chow diet. Results The results were compared with atherogenic initiation induced by high fat high fructose (HFHF) diet. The combined effects of HFHF and PMCD on atherogenic initiation were also investigated for possible synergy of both variants. The HFHF and HFHF+PMCD groups recorded increments in body weight gains and serum lipid parameters (TC, TG, LDL-cholesterol, VLDL) and a decrement in HDL-cholesterol as compared to the control group. However, PMCD group recorded body weight gain similar to that of the control group, but the serum lipid parameters (TG and VLDL) were significantly elevated and the HDL levels were lowered. However, prominent hypertrophic remodeling, higher collagen deposition, and elastin derangement, along with endothelial dysfunction, its activation, and macrophage infiltration, were observed in thoracic aorta of all the three experimental groups. But the mRNA and immunoblots of heat shock protein 60 (HSP60) in thoracic aorta was found to be maximum in PMCD followed by HFHF and HFHF+PMCD groups. Conclusion Laboratory chow feeding coupled with photoperiodic manipulation mediated chronodisruption overexpress HSP60 that in turn plays a central role in PMCD mediated pro-atherogenic remodeling in thoracic aorta of C57BL/6J mice.

Keywords

• Atherosclerosis
• HSP60
• Chronodisruption
• Vascular remodeling
• High fat high fructose diet