Chen Yu, You Yiran, Wang Xin, Jin Yufeng, Zeng Yupeng, Pan Zhijun, Li Dan, Ling Wenhua
Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China.
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China.
Nutrients. 2024 Dec 30;17(1):111. doi: 10.3390/nu17010111.
Atherosclerotic calcification (AC) is a common feature of atherosclerotic cardiovascular disease. β-Hydroxybutyrate (BHB) has been identified as a molecule that influences cardiovascular disease. However, whether BHB can influence AC is still unknown.
In this study, ApoE mice, fed a Western diet, were used to examine the effects of BHB on AC. Rat vascular smooth muscle cells (VSMCs) were used to verify the impacts of BHB on AC and to explore the underlying mechanisms. The results show that Western diet-challenged ApoE mice, supplemented with BHB for 24 weeks, exhibited reduced calcified areas, calcium content, and alkaline phosphatase (ALP) activity in the aortas, as well as ameliorated severity of AC. Furthermore, BHB downregulated the expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), thereby reducing endoplasmic reticulum stress (ERS) and ERS-mediated apoptosis in the aortas of the mice. Consistently, in vitro studies showed that BHB reduced ALP activity and calcium content in VSMCs, and inhibited VSMC calcification. Additionally, BHB suppressed ERS-mediated apoptosis in VSMCs.
In summary, the present results demonstrate that BHB can alleviate atherosclerotic calcification by inhibiting ERS-mediated apoptosis. Therefore, BHB may serve as a viable therapeutic agent for AC.
动脉粥样硬化钙化（AC）是动脉粥样硬化性心血管疾病的一个常见特征。β-羟基丁酸（BHB）已被确认为一种影响心血管疾病的分子。然而，BHB是否能影响AC仍不清楚。
在本研究中，给喂食西方饮食的载脂蛋白E（ApoE）小鼠补充BHB，以研究其对AC的影响。使用大鼠血管平滑肌细胞（VSMCs）来验证BHB对AC的影响并探索其潜在机制。结果显示，在接受西方饮食的ApoE小鼠中补充BHB 24周后，主动脉中的钙化区域、钙含量和碱性磷酸酶（ALP）活性降低，AC的严重程度得到改善。此外，BHB下调了葡萄糖调节蛋白78（GRP78）和C/EBP同源蛋白（CHOP）的表达，从而减轻了小鼠主动脉中的内质网应激（ERS）及ERS介导的细胞凋亡。同样，体外研究表明，BHB降低了VSMCs中的ALP活性和钙含量，并抑制了VSMCs钙化。此外，BHB抑制了VSMCs中ERS介导的细胞凋亡。
总之，目前的结果表明，BHB可通过抑制ERS介导的细胞凋亡来减轻动脉粥样硬化钙化。因此，BHB可能是一种治疗AC的有效药物。
