心肌梗塞增加了内分泌网膜压力和心脏和大脑中的蛋白质聚合,以及大脑
Nirjal Mainali1,2, Xiao Li3, Xianwei Wang3
1Bioinformatics Program, University of Arkansas at Little Rock and University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
Molecular and cellular biochemistry
|November 3, 2023
概括
心肌梗塞 (MI) 增加了心脏和大脑中的蛋白质聚合,可能导致类似阿尔茨海默氏症的认知障碍. 介质干细胞外体可以减少这种聚合和内细胞网膜压力.
科学领域:
- 心血管生物学 心血管生物学
- 神经科学是一个神经科学.
- 蛋白质生物化学 蛋白质生物化学
背景情况:
- 心血管疾病,如心肌梗塞 (MI),是全球主要的死亡原因.
- 蛋白质聚合与衰老和神经退行性疾病 (如阿尔茨海默氏症) 有关.
- 以前的研究表明,老化和高血压小鼠心脏中蛋白质聚合升高,但MI对心脏和大脑聚合的影响尚不清楚.
研究的目的:
- 为了研究实验性心肌梗塞 (MI) 对小鼠心脏和大脑中的蛋白质聚合的影响.
- 为了确定这些聚合物中的蛋白质成分.
- 评估介质干细胞 (MSC) 外体在缓解MI诱导聚合和相关压力的潜力.
主要方法:
- 在小鼠中通过左冠状动脉 (LCA) 绑定诱导MI,以假MI作为对照.
- 从心脏病发作的心脏组织和整个大脑中分离和净化不溶于洗剂的聚合物,在MI后7天.
- 使用高分辨率液体染色学-并联质谱法 (LC-MS/MS) 量化蛋白质成分.
- 评估内等质网膜 (ER) 压力标志物 (GRP78,ATF6,P-PERK).
主要成果:
- 与非心脏病发作或假心脏病发作组织相比,心脏病发作的心脏组织表现出明显更高的蛋白质聚合物水平 (2.5至10倍的增加).
- 肌痛发作诱导的大脑聚合物的蛋白质成分与人类AD大脑中发现的蛋白质成分有相当大的重叠.
- 通过MSC外基因组治疗,心脏聚合率降低了约60%,心脏和大脑的ER压力标志物减弱了50-75%.
- 在AD中常见的MI增加的聚合成分,包括蛋白质体子单元,热冲击蛋白和阿波利波蛋白.
结论:
- 实验性MI显著增加了小鼠的心脏和大脑中的蛋白质聚合.
- 发作性心脏病诱导的大脑聚合与人类阿尔茨海默氏症有共同成分,这表明与认知障碍有联系.
- MSC外体治疗有效地减少心脏聚合,并缓解心脏和脑组织后心脏和脑组织的ER压力.
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