Simo Olivier Kamtchueng, Berrougui Hicham, Fulop Tamas, Khalil Abdelouahed
Program of Physiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 1N1, Canada.
Department of Biology, Polydisciplinary Faculty, University Sultan Moulay Slimane, BP 592, Beni Mellal 23000, Morocco.
Biomedicines. 2021 Apr 29;9(5):487. doi: 10.3390/biomedicines9050487.
The anti-atherogenic activity of HDL is mainly due to their capacity to mediate reverse cholesterol transport (RCT). However, it is not clear to what extent this activity is affected by aging or pro-atherogenic conditions. Three and 24-month-old C57Bl/6 mice were fed an atherogenic diet (high fat, high cholesterol) for 12 weeks. The aged mice displayed a significant reduction in the capacity of HDL to mediate RCT (29.03%, < 0.0006). Interestingly, the atherogenic diet significantly stimulated the RCT process in both young and aged mice (241% and 201%, respectively, < 0.01). However, despite this, significant amounts of cholesterol accumulated in the aortas of mice fed an atherogenic diet as compared to regular chow. The accumulation of cholesterol was more marked in the aortas of aged mice (110% increase, < 0.002). ABCA1 and ABCG1 protein expression on macrophages decreased significantly (52 to 37% reduction, < 0.002), whereas their expression on hepatic cells increased significantly (up to 590% for ABCA1 and 116% for ABCG1, < 0.002). On the other hand, SR-BI protein expression on hepatic cells decreased significantly (42.85%, < 0.0001). ABCG5, ABCG8, and CYP7a protein expression on hepatic cells was also higher in mice fed an atherogenic diet. The increase was age-dependent for both ABCG5 and ABCG8. Our results suggest that the susceptibility to diet-induced atherosclerosis is exacerbated with aging and is a consequence of the dysregulation of the expression levels of membrane cholesterol transporters.
高密度脂蛋白（HDL）的抗动脉粥样硬化活性主要归因于其介导逆向胆固醇转运（RCT）的能力。然而，目前尚不清楚这种活性在多大程度上受到衰老或促动脉粥样硬化条件的影响。将3个月和24个月大的C57Bl/6小鼠喂食致动脉粥样硬化饮食（高脂肪、高胆固醇）12周。老年小鼠的HDL介导RCT的能力显著降低（29.03%，<0.0006）。有趣的是，致动脉粥样硬化饮食显著刺激了年轻和老年小鼠的RCT过程（分别为241%和201%，<0.01）。然而，尽管如此，与正常饲料相比，喂食致动脉粥样硬化饮食的小鼠主动脉中仍积累了大量胆固醇。胆固醇的积累在老年小鼠的主动脉中更为明显（增加110%，<0.002）。巨噬细胞上ABCA1和ABCG1蛋白表达显著降低（降低52%至37%，<0.002），而它们在肝细胞上的表达显著增加（ABCA1高达590%，ABCG1为116%，<0.002）。另一方面，肝细胞上SR-BI蛋白表达显著降低（42.85%，<0.0001）。喂食致动脉粥样硬化饮食的小鼠肝细胞上ABCG5、ABCG8和CYP7a蛋白表达也更高。ABCG5和ABCG8的增加均与年龄有关。我们的结果表明，饮食诱导的动脉粥样硬化易感性随衰老而加剧，是膜胆固醇转运蛋白表达水平失调的结果。
