载脂蛋白 A-V 对心肌细胞脂质蓄积调节的作用及其机制。
Effects and mechanisms of apolipoprotein A-V on the regulation of lipid accumulation in cardiomyocytes.
机构信息
Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Department of The Second Chest Medicine, The Affiliated Cancer Hospital of Xiangya School of medicine, Central South University, Changsha, Hunan, 410013, China.
出版信息
Lipids Health Dis. 2018 Mar 12;17(1):46. doi: 10.1186/s12944-018-0692-x.
BACKGROUND
Apolipoprotein (apo) A-V is a key regulator of triglyceride (TG) metabolism. We investigated effects of apoA-V on lipid metabolism in cardiomyocytes in this study.
METHODS
We first examined whether apoA-V can be taken up by cardiomyocytes and whether low density lipoprotein receptor family members participate in this process. Next, triglyceride (TG) content and lipid droplet changes were detected at different concentrations of apoA-V in normal and lipid-accumulation cells in normal and obese animals. Finally, we tested the levels of fatty acids (FAs) taken up into cardiomyocytes and lipid secretion through [C]-oleic acid.
RESULTS
Our results show that heart tissue has apoA-V protein, and apoA-V is taken up by cardiomyocytes. When HL-1 cells were transfected with low density lipoprotein receptor (LDLR)-related protein 1(LRP1) siRNA, apoA-V intake decreased by 53% (P<0.05), while a 37% lipid accumulation in HL-1 cells remain unchanged. ApoA-V localized to the cytoplasm and was associated with lipid droplets in HL-1 cells. A 1200 and 1800 ng/mL apoA-V intervention decreased TG content by 28% and 45% in HL-1 cells, respectively and decreased TG content by 39% in mouse heart tissue (P<0.05). However, apoA-V had no effects on TG content in either normal HL-1 cells or mice. The levels of FAs taken up into cardiomyocytes decreased by 43% (P < 0.05), and the levels of TG and cholesterol ester secretion increased by 1.2-fold and 1.6-fold, respectively (P < 0.05).
CONCLUSION
ApoA-V is a novel regulator of lipid metabolism in cardiomyocytes.
背景
载脂蛋白 A-V（apoA-V）是甘油三酯（TG）代谢的关键调节因子。本研究旨在探讨 apoA-V 对心肌细胞脂代谢的影响。
方法
首先，我们研究了 apoA-V 是否能被心肌细胞摄取，以及 LDL 受体家族成员是否参与这一过程。接下来，我们在正常和肥胖动物的正常和脂质蓄积细胞中，检测了不同浓度 apoA-V 对 TG 含量和脂滴变化的影响。最后，我们通过[C]-油酸检测了心肌细胞摄取脂肪酸（FAs）和脂质分泌的水平。
结果
研究结果表明，心脏组织中含有 apoA-V 蛋白，且 apoA-V 能被心肌细胞摄取。当 HL-1 细胞转染 LDLR 相关蛋白 1（LRP1）siRNA 后，apoA-V 摄取减少了 53%（P<0.05），而 HL-1 细胞中的脂蓄积则保持不变。apoA-V 定位于细胞质，并与 HL-1 细胞中的脂滴相关。1200 和 1800ng/mL apoA-V 干预分别使 HL-1 细胞中的 TG 含量减少了 28%和 45%，使小鼠心脏组织中的 TG 含量减少了 39%（P<0.05）。然而，apoA-V 对正常 HL-1 细胞或小鼠的 TG 含量均无影响。心肌细胞摄取的 FAs 水平减少了 43%（P < 0.05），而 TG 和胆固醇酯的分泌水平分别增加了 1.2 倍和 1.6 倍（P < 0.05）。
结论
apoA-V 是心肌细胞脂代谢的一种新型调节因子。
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