Human Ventricular Myosin Light Chain Isotype 1 as a Marker of Myocardial Injury

Abstract

A monoclonal enzyme immunoassay for measuring human ventricular myosin light chain isotype 1 (HVMLC1) in serum has been developed. To evaluate the method in patients with suspected myocardial injury, we studied 51 patients (16 acute myocardial infarction (AMI), 19 unstable angina pectoris (UAP), 9 stable angina pectoris, 3 nonischemic heart disease, 4 hip surgery patients), and 190 controls (blood donors). Serial blood-samples were drawn from patients; a single blood-sample from controls. The diagnostic value of the HVMLC1 assay was compared with total creatine kinase (CK), CKMB activity, CKMB mass concentration, lactate dehydrogenase isoenzyme 1 (LD1), troponin T (TnT) and mitochondrial-aspartate aminotransferase (m-ASAT). The detection limit of HVMLC1 was 0.4 µg/l (linear range 0-20 µg/l). Sera from 190 reference persons did not contain detectable levels of HVMLC1 ( < 0.4 µg/l; 99% percentile). The coefficients of variation were 13% (1.0 µg/l) and 3.1% (17.7 µg/l). Cross-reactivity with myosin from skeletal muscle was seen. Times to peak value were: CK 19.3 ± 2.0, LD1 43.4 ± 3.2, HVMLC1 72.9 ± 7.0, and m-ASAT 67.3 ± 5.6 h. Time-curves of HVMLC1 and m-ASAT were similar, whereas time-curves for HVMLC 1 and TnT were quite different in most cases. Peak value of HVMLC 1 was five times higher than CK peak value and eight times that of LD1. HVMLC 1 appeared in the blood within hours after the onset of chest pain and in the majority remained for more than a week after AMI. Among patients with UAP 16% (3/19) had elevated HVMLC1 in serum, whereas elevated TnT was seen in 26% (5/19) and elevated CKMB mass in 26% (5/19). We conclude that the new HVMLC 1 assay offers a sensitive diagnosis of myocardial injury. It is characterized by a wide diagnostic time window. The similarity of the HVMLC 1 and m-ASAT curves indicates that it may be used to estimate the extent of myocardial necrosis.

Autoantigens Identified by Screening a Human Heart cDNA Library with Acute Rheumatic Fever Sera

“…It is composed of two heavy chains, two phosphorylatable regulatory light chains, and two non‐phosphorylatable essential alkali light chains. The regulatory light chains have disease links with familial hypertrophic cardiomyopathy, 18 while the alkali light chains are involved in actin binding and are a known biomarker of cardiac injury 19 …”

“…The regulatory light chains have disease links with familial hypertrophic cardiomyopathy, 18 while the alkali light chains are involved in actin binding and are a known biomarker of cardiac injury. 19…”

Combined subthreshold dose inhibition of myosin light chain phosphorylation and MMP‐2 activity provides cardioprotection from ischaemic/reperfusion injury in isolated rat heart

“…Consistent with this, our model of I/R injury has consistently shown loss of MLC1 from myocardium, which was detected in the effluent (Sawicki et al ., ; Cadete et al ., ). These observations are consistent with previous reports in which MLC1 has been validated as a serum marker of myocardial injury (Ravkilde et al ., ; Omura et al ., ). Additionally, we have shown that creatine kinase (CK) is increased (200‐fold) in our I/R injury model and can be rescued with MMP‐2 inhibition (Fert‐Bober et al ., 2008b).…”