Inverse changes in plasma tetranectin and titin levels in patients with type 2 diabetes mellitus: a potential predictor of acute myocardial infarction?

Abstract

An early intervention using biomarkers to predict acute myocardial infarction (AMI) will effectively reduce global heart attack incidence, particularly among high-risk patients with type 2 diabetes mellitus (T2DM). This study attempted to identify potential biomarkers by detecting changes in the levels of plasma proteins in T2DM patients following onset of AMI in comparison with those without AMI. Volunteer T2DM patients without AMI (control; n=10) and T2DM patients with AMI (n=10) were recruited. Plasma samples from these patients were evaluated via two-dimensional gel electrophoresis (2DE) to screen for proteins with level changes between the two groups. The abundance of spots on gel images was analyzed using Progenesis SameSpots and subjected to false discovery rate (FDR) analysis. Protein spots with statistically significant changes of at least 1.5 fold were selected for mass spectrometry (MS) analysis. Due to strong cardiac connections, tetranectin and titin were evaluated by enzymelinked immunosorbent assay (ELISA). The adjusted P-values and fold changes between the two groups resulted in identification of 34 protein spots with significantly altered abundance. Upon MS analysis, 17 plasma proteins were identified: tetranectin, titin, clusterin, haptoglobin, myosin-13, zinc fnger protein 445, DNA repair protein RAD50, serum albumin, apolipoprotein A-IV, caspase-6, aminoacyl tRNA synthase complex-interacting multifunctional protein 1, serotransferrin, retinol-binding protein 4, transthyretin, alpha-1-antitrypsin, apolipoprotein A-I and serum amyloid A. Comparable patterns of changes in tetranectin and titin between the control and AMI groups were confirmed using ELISA. In summary, tetranectin and titin in plasma appeared to be closely associated with the onset of AMI among T2DM patients and can be used as potential biomarkers for prediction of a cardiac event, though this requires validation in a prospective cohort study.

Urinary Titin Is Increased in Patients After Cardiac Surgery

“…More recently, Yoshihisa et al reported that urinary N-terminal fragment (N-titin) of titin, a giant sarcomeric protein that is involved in muscular passive tension and viscoelasticity, could be a biomarker for predicting high risk dilated cardiomyopathy patients (6) by using the enzyme-linked immunosorbent assay (ELISA) system (7). In accordance with this finding, plasma titin is closely associated with the onset of acute myocardial infarction in patients with type 2 diabetes mellitus (8).…”

Obscurin and Clusterin Elevation in Serum of Acute Myocardial Infarction Patients

“…Twelve proteins among 23 were reported with acute inflammation, heart failure, thrombosis, and cardiac diseases . Transthyretin, hemoglobin subunit alpha, beta, antithrombin III, serum amyloid P‐component, fibrinogen α, ß, γ, alpha‐1‐acid glycoprotein 1 and 2, apolipoprotein A‐II, and serotransferrin are relatively highly abundant proteins in human serum and therefore already known biomarkers for cancer, inflammation, cardiac hypertrophy, and heart failure . Some proteins are known as muscle or cardiac muscle components, such as complement C‐4A, C3, obscurin, and titin …”

Circulating biomarkers for cardiovascular diseases: the beats never stop

“…Accordingly, this Special Issue of Acta Pharmacologica Sinica was planned to provide a forum for high quality original research and review articles to showcase the most recent advances in translational research and clinical practices on a wide-spectrum array of conventional as well as novel cardio-vascular biomarkers. Coverage of this Special Issue encompasses various forms of large or small molecules, such as proteins, peptides, cytokines, microRNAs, and metabolic by- This Special Issue covers a variety of pathological types of CVD, including acute myocardial infarction (AMI) [2][3][4][5] , heart failure [6] , aortic aneurysms [7,8] , carotid restenosis [9] , pulmonary arterial hypertension (PAH) [10] , and cardiac amyloidosis [11] . Several review articles provided in-depth analyses on the important diagnostic and prognostic roles of zinc [12] , oxylipins [13] , and leptin [14] in the fundamental cellular signaling and pathogenic processes in CVD and diabetes.…”

“…Several review articles provided in-depth analyses on the important diagnostic and prognostic roles of zinc [12] , oxylipins [13] , and leptin [14] in the fundamental cellular signaling and pathogenic processes in CVD and diabetes. Notably, all the 7 original research articles are clinical research on Asian patients with AMI [5] or PAH [10] as well as European patients with AMI [2] , chronic heart failure [6] , vascular aneurysm [7] or restenosis [9] , and stroke [15] .…”

“…Another highlighted area of discussion in this Special Issue is on the technological and methodological innovations for the CVD biomarker detection. Our invited experts have communicated their original research results using various technologies from advanced chip-based digital PCR [2] to 2D-gel analysis [5] . They also thoroughly reasoned the needs for multiplex approach to enhance diagnostic accuracy superior to the single biomarker detection [19] .…”