January 16, 2018

Distinctive molecular signature and activated signaling pathways in aortic smooth muscle cells of patients with myocardial infarction

DOI: http://dx.doi.org/10.1016/j.atherosclerosis.2018.01.024

Atherosclerosis, manuscript in the press, accepted 16 January, 2028

Thidathip Wongsurawat, Chin Cheng Woo, Antonis Giannakakis, Xiao Yun Lin, Esther Sok Hwee Cheow, Chuen Neng Lee, Mark Richards, Siu Kwan Sze, Intawat Nookaew, Vladimir A. Kuznetsov’Correspondence information about the author Vladimir A. Kuznetsov, Vitaly Sorokin


Background and aims: We aim to identify significant transcriptome alterations of vascular smooth muscle cells (VSMCs) in the aortic wall of myocardial infarction (MI) patients. Providing a robust transcriptomic signature, we aim to highlight the most likely aberrant pathway(s) in MI VSMCs. Methods and results: Laser-captured microdissection (LCM) was used to obtain VSMCs from aortic wall tissues harvested during coronary artery bypass surgery. Microarray gene analysis was applied to analyse VSMCs from 17 MI and 19 non-MI patients. Prediction Analysis of Microarray (PAM) identified 370 genes that significantly discriminated MI and non-MI samples and were enriched in genes responsible for muscle development, differentiation and phenotype regulation. Incorporation of gene ontology (GO) led to the identification of a 21-gene VSMCs-associated classifier that discriminated between MI and non-MI patients with 92% accuracy. The mass spectrometry-based iTRAQ analysis of the MI and non-MI samples revealed 94 proteins significantly differentiating these tissues. Ingenuity Pathway Analysis (IPA) of 370 genes revealed top pathways associated with hypoxia signaling in the cardiovascular system. Enrichment analysis of these proteins suggested an activation of the superoxide radical degradation pathway. An integrated transcriptome-proteome pathway analysis revealed that superoxide radical degradation pathway remained the most implicated pathway. The intersection of the top candidate molecules from the transcriptome and proteome highlighted superoxide dismutase (SOD1) overexpression

Conclusions: We provided a novel 21-gene VSMCs-associated MI classifier in reference to significant VSMCs transcriptome alterations that, in combination with proteomics data, suggests the activation of superoxide radical degradation pathway in VSMCs of MI patients.