Cardiovascular Research Unit, Hospital Clínico San Carlos, Madrid, Spain.
J Cardiovasc Electrophysiol. 2010 Aug 1;21(8):859-68. doi: 10.1111/j.1540-8167.2010.01718.x. Epub 2010 Feb 2.
The objective was to compare by proteomics the expression of proteins associated with the cytoskeleton, energetic metabolism, and cardiac cytoprotection between left atrial appendages (LAA) and right atrial appendages (RAA) obtained from patients with mitral valve disease both in sinus rhythm (SR, n = 6) and in permanent atrial fibrillation (AF, n = 11).
Samples from RAA and LAA were obtained from the same patient. Proteins were separated in 2-dimensional electrophoresis and identified by mass spectrometry. LAA from SR patients upexpressed alpha-actin isotype 1 and desmin isotypes 3 and 5 with respect to RAA. In LAA from AF patients were upexpressed cardiac alpha-actin isotypes 1 and 2, tropomyosin alpha- and beta-chains, and myosin light chain embryonic muscle/atrial isoform with respect to LAA from SR patients. In RAA from AF patients also upexpressed different cytoskeleton associated proteins with respect to RAA from SR patients. Different energetic metabolism-associated proteins were upexpressed in LAA and RAA from AF with respect those from SR patients. In AF patients, the expression of proteins associated with cardiac cytoprotection such as gluthatione-S-transferase, heat shock protein (Hsp) 27, and different Hsp60 isotypes, were higher in RAA but not in LAA with respect to the corresponding appendages in SR patients.
For each individual patient RAA and LAA showed a similar level of proteins expressed associated with cytoskeleton, energetic metabolism, and cardiac cytoprotection. There were more differences in the level of proteins associated with the above-mentioned mechanisms between the atrial appendages from AF with respect to SR patients, which may open new targets for drugs.
目的是通过蛋白质组学比较在窦性心律(SR,n=6)和永久性心房颤动(AF,n=11)患者的左心耳(LAA)和右心耳(RAA)中与细胞骨架、能量代谢和心脏细胞保护相关的蛋白质的表达。
从同一患者获得 RAA 和 LAA 的样本。蛋白质在二维电泳中分离,并通过质谱鉴定。与 RAA 相比,SR 患者的 LAA 中α-肌动蛋白同工型 1 和结蛋白同工型 3 和 5 表达上调。在 AF 患者的 LAA 中,与 SR 患者的 LAA 相比,心脏α-肌动蛋白同工型 1 和 2、原肌球蛋白α和β链以及肌球蛋白轻链胚胎/心房同工型表达上调。在 AF 患者的 RAA 中,与 SR 患者的 RAA 相比,还表达了不同的细胞骨架相关蛋白。与 SR 患者相比,AF 患者的 LAA 和 RAA 中不同的能量代谢相关蛋白表达上调。在 AF 患者中,与 SR 患者相比,与心脏细胞保护相关的蛋白质,如谷胱甘肽-S-转移酶、热休克蛋白(Hsp)27 和不同的 Hsp60 同工型的表达在 RAA 中更高,但在 LAA 中没有。
对于每个个体患者,RAA 和 LAA 显示出相似水平的与细胞骨架、能量代谢和心脏细胞保护相关的表达蛋白。在 AF 患者与 SR 患者相比,心房附属物中与上述机制相关的蛋白水平存在更多差异,这可能为药物提供新的靶点。