Abstract
BackgroundTitin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical setting, we aimed to develop an assay that could reliably measure fragments of degraded titin in serum and potentially be used in the assessment of cardiac muscle damage.MethodsA competitive ELISA was developed to specifically measure levels of the titin sequence 12670’ NVTVEARLIK 12679’, derived by the degradation of titin by matrix metalloproteinase (MMP)-12. Serum samples from 90 individuals were divided into 3 equally sized groups. One group had been diagnosed with acute myocardial infarction (AMI) while the remaining two were asymptomatic individuals either with CT-scan signs of coronary calcium (CT-plusCa) or without coronary calcium (CT-noCa).ResultsMean geometric levels of the titin fragment in the CT-noCa group were 506.5 ng/ml (±43.88). The CT-plusCa group showed 50.6% higher levels of the marker [763 ng/ml (±90.14)] (P < 0.05). AMI patients showed 56.3% higher levels [792 ng/ml (±149)] (P < 0.05).ConclusionsThe titin-12670 fragment is present in both individuals with undiagnosed and diagnosed CVD. The statistically significant increase in level of the marker in the AMI group is indicative that this neoepitope biomarker may be a useful serological marker in AMI.
Highlights
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension
Examples of cardiac markers based on troponin, a protein which is in close proximity to and interacts with titin, indicate that release of myocyterelated protein remodeling fragments into the circulation can provide accurate markers of pathology-related remodeling. We investigated this hypothesis by developing a monoclonal antibody and a serum-based assay for the identification of the titin fragment degenerated by matrix metalloproteinase (MMP)-12
Clone characterization & tissue specificity The clone selected for Enzyme linked immunosorbent assay (ELISA) development was determined to be the IgG1 subtype
Summary
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Known as connectin, is a sarcomeric protein expressed in cardiac and skeletal muscle. It is the largest known protein in nature, with a molecular weight of up to 3700 kDa [1]. Its main function in the heart is to act as a long molecular spring by restoring passive tension during myocardial stretch and enhancing or terminating active force regulating the Frank-Starling mechanism of the heart [2,3,4,5]. The studies rely on invasive tissue extractions which are analysed by methods such as immunoblotting and gel electrophoresis
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