IDENTIFICATION OF SIGNATURE MOLECULAR BIOMARKERS FOR THERAPEUTIC TARGETING FOR CARDIOVASCULAR DISEASES BY NETWORK BASED ANALYSIS

Abstract

The Cardiovascular diseases are the age-related diseases and their genesis is not only affiliated with the accumulation of lipids in the cardiac vessels but more to the inflammatory process. In this study, while focusing on the therapeutic significance, a systems and computational biology strategy was utilized to examine biomarkers central to myocardial inflammation and analyze various regulatory networks monitoring the process. In tissue-specific gene co-expression assessment, CCL2, IL6 and IL8 were revealed as the central hub genes in atrial appendage and CCL2 was shown to be the major hub gene in left ventricle. Consequently, CCL2 was the master gene since it was expressed by both of the cardiac tissues. Moreover, in gene-miRNA interaction analysis, the post-transcriptional regulator hsa-miR-155-5p was identified as the primary regulator, furthermore, in gene-transcription factor (TF) interaction examination, NFƘB1 was found to be the key regulator. The expression of CCL2, IL6 and IL8 (all cytokines) creates an intensified inflammatory cycle. The hub post-transcriptional regulator hsa-miR-155 5p and transcription factor NFƘB1 are observed to be associated with CCL2 and IL6 so, can be considered as crucial regulatory points and hub biomarkers which can be targeted for therapeutics as all are playing major role in inflammatory signalling pathways. The CCL2 CCR2 and IL6-IL6R signalling axes can be obstructed by designing CCL2 and IL6 specific antibodies which can neutralize them or designing CCL2R and IL6R antagonists, and hsa-miR 155-5p and NFƘB1 can also be targeted by designing their inhibitor molecules. Moreover, the drugs- Tocilizumab, Canakinumab, Adalimumab, Methotrexate, Colchicine and Rosuvastatin addresses these biological markers which are associated with inflammation. Therefore, these can be the novel and potential biomarkers which can be targeted for achieving broad-spectrum therapeutics and by targeting these signature biomarkers, we can intervene the inflammatory signalling pathways at multiple levels thus, reducing the risk of pathogenesis of major fatal CVDs.