Proteomic Approach to Discover Potential Biomarkers for Heart Failure

Abstract

Heart failure is a clinical syndrome that develops due to abnormality in the cardiac structure or mechanical function leading to failure of the heart to deliver oxygen at a rate proportionate with the requirements of the metabolizing tissues. Despite advancement in primary prevention and therapy, it had continued to record poor prognosis and more complications leading to high rate of mortality. Recent advances in proteomic technologies permit the evaluation of systemic changes in protein expression in response to intrinsic or extrinsic perturbations to the biologic system. Proteomics is a potential tool for the discovery and application of novel biomarkers in diagnosis of the inception and progression of cardiovascular diseases (CVDs) which might then affect prevention and therapy. Shotgun proteomic approach was utilized to identify and compare the proteins in the tissue samples of a 3 month old glucokinase knockout mouse in early stage heart failure with a normal control mouse tissue sample. Bioinformatics analysis was performed using the MASCOT MS/MS ions search to identify, characterize and quantify. A total of 156 cardiac proteins were found in the normal control mouse tissue sample while 163 cardiac proteins were found in the diseased mouse tissue sample. 104 common cardiac proteins were identified in both mouse tissue samples. 35 cardiac proteins out of the common cardiac proteins were differentially expressed in the diseased mouse tissue sample and 49 unique cardiac proteins were also found in the diseased mouse tissue sample. 6 cardiac proteins (ATP Synthase mitochondrial OS, Cytochrome C somatic OS, Myoglobin OS, Myosin-6 OS, Isocitrate dehydrogenase (NADP) mitochondrial OS and Histone H4 OS with high exponentially modified protein abundance index (emPAI) from the differentially expressed and unique cardiac proteins were selected as potential discovered biomarkers. The selected proteins play an important role in cellular stress response, mitochondrial dysfunction and myocardial cell death.