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在慢性和病理衰老期间,心脏细胞外矩阵蛋白质的重塑

Deolinda Santinha¹, Andreia Vilaça², Luís Estronca¹

¹Faculty of Medicine, University of Coimbra, Celas, Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Rua Larga, Coimbra, Portugal.

Molecular & cellular proteomics : MCP

|December 23, 2023

概括

衰老会影响心脏细胞外矩阵 (ECM) 的重塑. 乳腺在老年心血管中的积累会触发内皮细胞的炎症反应,将ECM变化与细胞衰老联系起来.

科学领域:

心血管生物学心血管生物学
衰老研究研究衰老研究
蛋白质组学是指蛋白质组学.

背景情况:

损坏的细胞外基质 (ECM) 改造与慢性炎症,细胞功能障碍和疾病进展有关.
老年心脏的ECM及其对心脏细胞在衰老过程中的影响尚不清楚.

研究的目的:

在慢性和病理衰老期间,对老鼠和人类左心室 (LV) 的与年龄相关的ECM重塑进行定量描述.
研究特定的ECM蛋白对心脏细胞的影响.

主要方法:

基于质谱的蛋白质组学来分析心脏"母体" (ECM和相关蛋白质).
在年轻与老年小鼠和人类LV中ECM蛋白质配置文件的比较,包括在Hutchinson-Gilford孕症综合征 (HGPS) 模型中.
在体外研究中,大动脉内皮细胞 (ECs) 暴露于固定乳腺素.

主要成果:

确定了13种与年龄相关的ECM蛋白质,其中乳腺素 (MFGE8),原VIα6 (COL6A6),维特龙菌素 (VTN) 和免疫球蛋白重常数mu (IGHM) 增加,而纤维素-5 (FBLN5) 减少.
在老年心血管中观察到乳素的积累.
固定乳腺素诱导了GSK3B,MAPK和MTOR激酶的酸化,并在大动脉EC中增加了促炎标志物.

结论:

在不同物种中,LV蛋白质组的与年龄相关的变化具有特征.
乳腺素在内皮细胞中引发炎症和衰老表型的作用突显了ECM重塑和心脏衰老之间的联系.
这些发现为预防心脏衰老提供了潜在的目标.

关键词:

哈森-吉尔福德预后综合征是什么?衰老的衰老衰老的衰老心脏衰老的心脏衰老脱细胞化脱细胞化细胞外矩阵是细胞外矩阵.乳腺素是一种乳腺素.一个母体组的母体组.蛋白质基质的保护性

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