Secretome analysis of atherosclerotic and non-atherosclerotic arteries reveals dynamic extracellular remodeling during pathogenesis

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• 作者：Fernando de la Cuesta^a ; ¹ ; Maria G. Barderas^b ; ¹ ; Enrique Calvo^c ; Irene Zubiri^a ; Aroa S. Maroto^a ; Veronica M. Darde^b ; Tatiana Martin-Rojas^b ; Felix Gil-Dones^b ; Maria Posada-Ayala^a ; Teresa Tejerina^d ; Juan A. Lopez^c ; Fernando Vivanco^a ; ^e ; ² ; Gloria Alvarez-Llamas^a ; ² ; ^{galvarez@fjd.es}
• 关键词：Vascular disease ; Atheroma plaque ; Secretome ; Coronary artery
• 刊名：Journal of Proteomics
• 出版年：2012
• 期刊代码：P37_18743919
• 类别：ch
• 出版时间：6 June, 2012
• 卷：75
• 期：10
• 页码：2960-2971
• 文件大小：1881 K

摘要

Aims

Early detection of cardiovascular diseases and knowledge of underlying mechanisms is essential. Tissue secretome studies resemble more closely to the in vivo situation, showing a much narrower protein concentrations dynamic range than plasma. This study was aimed to the analysis of human arterial tissue secretome and to the quantitative comparison of healthy and atherosclerotic secretome to discover proteins with key roles in atherosclerosis development.

Methods and results

Secretomes from three biological replicates of human atherosclerotic coronary arteries (APC), preatherosclerotic coronaries (PC) and mammaries (M) were analyzed by LC-MS/MS. The identified proteins were submitted to Ingenuity Pathway Analysis (IPA) tool. Label-free MS/MS based quantification was performed and validated by immunohistochemistry. 64 proteins were identified in the 3 replicates of at least one of the 3 groups and 15 secreted proteins have not been previously reported in plasma. Four proteins were significantly released in higher amounts by mammary tissue: gelsolin, vinculin, lamin A/C and phosphoglucomutase 5.

Conclusion

The study of tissue secretome reveals key proteins involved in atherosclerosis which have not been previously reported in plasma. Novel proteins are here highlighted which could be potential therapeutic targets in clinical practice. This article is part of a Special Issue entitled: Proteomics: The clinical link.