Role of Troponin I Proteolysis in the Pathogenesis of Stunned Myocardium

Gao, Wei Dong; Atar, Dan; Liu, Yongge; Pérez, Néstor Gustavo; Murphy, Anne M.; Marbán, Eduardo

doi:10.1161/01.res.0000435855.49359.47

Cited by 360 publications

(154 citation statements)

References 40 publications

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“…The level of cTnI was increased and peaked in parallel with CK-MB activity, and the peak values correlated with each other. In contrast to cTnT, CK-MB, and LDH-1, cTnI is not expressed in skeletal muscle during fetal development, and an increase in cTnI has been reported only after myocardial damage [6,10,19,22,24]. cTnI is thus a serum marker with a high sensitivity and specificity for cardiac myocyte damage and can aid in the diagnosis of myocarditis or myocardial injury [12,25].…”

Section: Discussionmentioning

confidence: 99%

Elevation of Cardiac Troponin I in the Acute Stage of Kawasaki Disease

Kim¹,

Kim²

1999

Pediatr Cardiol

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The study was performed to investigate the level of serum cardiac troponin I (cTnI), a marker specific for myocardial damage, using a chemiluminescent immunoassay in the acute febrile stage of Kawasaki disease (KD). The study population consisted of 45 KD patients before intravenous gamma-globulin (IVGG) therapy and a control group of 20 patients without KD. Among KD patients the results from measurements of the level of cTnI were positive in 18 cases (40%) and the creatine kinase (CK)-MB was positive in 11 cases (24%), but in the control group both the cTnI and CK-MB results were negative. Seven KD patients (15.6%) showed increases in both cTnI and CK-MB that were significantly correlated with each other (p < 0.05); however, CK-MB is not heart-specific. A significant increase in the level of cTnI in the acute stage of KD suggests that acute myocarditis or myocardial cell injury begins in the early phase of the disease (p < 0.05). The serologic test for cTnI can thus be a useful method for the early diagnosis of acute myocarditis and may enable early treatment with IVGG to reduce the cardiovascular abnormalities in KD patients.

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Section: Discussionmentioning

confidence: 99%

Elevation of Cardiac Troponin I in the Acute Stage of Kawasaki Disease

Kim¹,

Kim²

1999

Pediatr Cardiol

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“…The myofilament proteins, including actin, myosin, tropomyosin, and troponin, are key mediators of contraction in cardiac muscle, and several studies have demonstrated that TnT and TnI in particular undergo specific and selective PTM in various forms of acute myocardial disease [2][3][4][5][6][7][8]. In order to include analysis of TnT modification in various models of cardiac disease using a proteomic approach, the 2-DE separation and detection of TnT and degraded TnT products was improved, through analysis of tissue from a rejected human donor transplant heart.…”

Section: Discussionmentioning

confidence: 99%

“…Extensive work in various animal models of myocardial injury and patients undergoing coronary artery bypass surgery has demonstrated that two subunits of the troponin complex, TnT [2][3][4][5] and TnI [5][6][7][8], undergo varying degrees of disease-induced post-translational modification (PTM). These include proteolytic degradation, formation of covalent complexes with each other, and, in the case of TnI, phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

Solubilization, two-dimensional separation and detection of the cardiac myofilament protein troponin T

Labugger¹,

McDonough²,

Neverova³

et al. 2002

Proteomics

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Proteomics strongly relies on the separation of complex protein mixtures, with two-dimensional electrophoresis (2-DE) being a commonly used technique. However efficient separation requires adequate solubilization of the original sample which will determine whether all proteins are accurately represented. Cardiac muscle has presented a particular challenge to solubilization. Here we have optimized the solubilization, separation and detection of the myofilament protein troponin T (TnT). Human left ventricular tissue from a rejected donor transplant heart was homogenized under 19 different conditions and subjected to 2-DE and Western blot analysis for TnT. The optimal conditions for isoelectric focusing of intact TnT requires homogenization in 6 M urea, 2.5 M thiourea, 4% 3-[(3-cholamidopropyl)dimethylamino]-1-propanesulfonate, with the addition of NaCl (2.5 M final concentration). TnT degradation products present in this severely damaged heart however, were differentially extracted from both each other and the intact molecule under the various conditions used. Despite adequate focusing of TnT it was found that a nonglutaraldehyde silver staining protocol, that is compatible with subsequent mass spectrometry, has greatly reduced sensitivity for TnT compared to Coomassie blue. Thus, care is required to avoid misrepresentation of troponin T in proteomic analysis in cardiac tissue.

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“…Moreover, the activity of calpain is enhanced in post-ischaemic reperfused myocardium [44,45]. In stunned myocardium there is a partial and selective degradation of the thin filament regulatory protein Tn I [46]. In striated muscles Tn I has a critical involvement in the ternary troponin complex.…”

Section: Stunningmentioning

confidence: 99%

125I-BMIPP and 18F-FDG uptake in a transgenic mouse model of stunned myocardium

Verberne

Sloof

Beets

et al. 2003

Eur J Nucl Med Mol Imaging

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Reported metabolic patterns in myocardial stunning are not uniform. We investigated relative myocardial perfusion, glucose and fatty acid uptake using a technetium-99 hexakis-2-methoxyisobutyl-isonitrile (MIBI), fluorine-18 2-fluoro-2-deoxyglucose (FDG) and iodine-125 15-(p-iodo-phenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) mixture, in a recently developed transgenic (TR) mouse model which mimics stunned myocardium. Twenty-seven mice - 14 TR and 13 age-matched wild type controls (C) - were divided into four groups: TR-fed, TR-fasted, C-fed and C-fasted. Animals were sacrificed 2 h after injection, tissue samples counted and percent-injected dose/gram tissue (% id/g) calculated for each radioisotope. Tissues were also Folch extracted and 125I incorporation into the various lipid pools (TG, triglycerides; DG, diglycerides; FFA, free fatty acids; PL, phospholipids) was determined by thin-layer chromatography (TLC). The pooled data for each of the four groups (TR-fed vs C-fed and TR-fed vs C-fasted) showed no differences in myocardial blood flow (% MIBI id/g), glucose uptake (% FDG id/g) or fatty acid uptake (% BMIPP id/g). Only minor differences were observed in the incorporation of 125I-BMIPP into the myocardial TG, DG, FFA and PL lipid pools. However, significantly decreased myocardial FDG uptake was observed in a subset of fasted mice - four out of ten TR-fasted mice (3.4% vs 20.5% id/g) and three out of nine C-fasted mice (5.5% vs 30.6% id/g). The transgenic mouse model of stunned myocardium shows normal myocardial perfusion and overall intact myocardial glucose and myocardial fatty acid uptake as determined with clinically applicable radiolabelled analogues. These data are in line with the hypothesis that the contractile inefficiency in stunned myocardium is not linked to metabolic alterations but is associated with an insufficient chemical to mechanical energy coupling.

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Role of Troponin I Proteolysis in the Pathogenesis of Stunned Myocardium

Cited by 360 publications

References 40 publications

Elevation of Cardiac Troponin I in the Acute Stage of Kawasaki Disease

Elevation of Cardiac Troponin I in the Acute Stage of Kawasaki Disease

Solubilization, two-dimensional separation and detection of the cardiac myofilament protein troponin T

125I-BMIPP and 18F-FDG uptake in a transgenic mouse model of stunned myocardium

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