The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523710, China.
Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
Molecules. 2023 Feb 10;28(4):1701. doi: 10.3390/molecules28041701.
Atherosclerosis (AS) is a common cardiovascular disease and remains the leading cause of death in the world. It is generally believed that the deposition of foam cells in the arterial wall is the main cause of AS. Moreover, promoting cholesterol efflux and enhancing the ability of reverse cholesterol transport (RCT) can effectively inhibit the formation of foam cells, thereby preventing the occurrence and development of AS. Astaxanthin, with a powerful antioxidant ability, has a potential role in the prevention of atherosclerosis, but how it works in preventing atherosclerosis remains unknown. Here, our experimental results suggest that astaxanthin can upregulate the expression of circular RNA tripeptidyl-peptidase II (circTPP2) and eventually promote cholesterol efflux by modulating ATP-binding cassette subfamily A member 1 (ABCA1). The expression of ABCA1 was significantly suppressed after knocking down circTPP2 in macrophage-derived foam cells. In addition, the experimental results showed that circTPP2 could downregulate the expression of microRNA-3073b-5p (miR-3073b-5p), and ABCA1 was identified as the target gene of miR-3073b-5p. In conclusion, the circTPP2/miR-3073b-5p/ABCA1 axis may be the specific mechanism of astaxanthin promoting cholesterol efflux.
动脉粥样硬化（AS）是一种常见的心血管疾病，仍然是世界上主要的死亡原因。人们普遍认为，动脉壁中泡沫细胞的沉积是 AS 的主要原因。此外，促进胆固醇外流和增强逆向胆固醇转运（RCT）的能力可以有效抑制泡沫细胞的形成，从而预防 AS 的发生和发展。虾青素具有强大的抗氧化能力，在预防动脉粥样硬化方面具有潜在作用，但它如何预防动脉粥样硬化尚不清楚。在这里，我们的实验结果表明，虾青素可以上调环状 RNA 三肽基肽酶 II（circTPP2）的表达，最终通过调节三磷酸腺苷结合盒亚家族 A 成员 1（ABCA1）促进胆固醇外流。在巨噬细胞源性泡沫细胞中敲低 circTPP2 后，ABCA1 的表达明显受到抑制。此外，实验结果表明，circTPP2 可以下调 microRNA-3073b-5p（miR-3073b-5p）的表达，ABCA1 是 miR-3073b-5p 的靶基因。总之，circTPP2/miR-3073b-5p/ABCA1 轴可能是虾青素促进胆固醇外流的特定机制。
