The coiled-coil domain of myosin-11 as a potential biomarker to detect patients with atherosclerotic cardiovascular disease risk

Abstract

BackgroundAtherosclerosis leads to severe clinical complications, and biomarkers that could predict its progression are highly desired. Phenotypic changes and dysregulation of smooth muscle cells contribute substantially to both subclinical and clinical atherosclerosis. Plasma levels of myosin-11, a smooth muscle cell-specific myosin, have been reported to increase in patients with clinical manifestations of atherosclerosis, including coronary artery disease and/or peripheral artery disease. This study aimed to investigate the association between circulating myosin-11 levels and atherosclerotic cardiovascular disease (ASCVD) risk in patients without symptomatic atherosclerosis. Methods and resultsThis prospective study recruited 161 participants: 80 patients with either hypertension, dyslipidemia, or diabetes mellitus but without symptomatic atherosclerosis (ASCVD risk group); 50 patients with ischemic heart disease (IHD group); and 31 control participants (Controls). We developed rat monoclonal antibodies specific for the coiled-coil domain of myosin-11 and quantified circulating myosin-11 levels using an enzyme-linked immunosorbent assay with these antibodies. Myosin-11 levels were highest in the IHD group, followed by the ASCVD risk group. Both groups had significantly higher myosin-11 levels than Controls. The area under the receiver-operating characteristic curve of myosin-11 was 0.980 for IHD versus Controls and 0.874 for ASCVD risk versus Controls. Univariate analysis detected significant associations between myosin-11 levels and hypertension and age. The association between myosin-11 levels and hypertension remained significant after multivariate logistic regression analysis. ConclusionsCirculating myosin-11 levels are elevated in patients with ASCVD risk. Myosin-11 levels may be a useful biomarker for stratification of asymptomatic individuals with higher risk of ASCVD. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIWe developed a sandwich enzyme-linked immunosorbent assay (ELISA) consisting of rat monoclonal antibodies specific for the coiled-coil domain of myosin-11 to detect trace concentrations of myosin-11 in blood circulation. C_LIO_LIPlasma myosin-11 concentrations were elevated in both asymptomatic individuals with traditional risk factors for atherosclerotic cardiovascular disease and in patients with symptomatic coronary atherosclerosis. C_LIO_LIThis elevation may be a potential marker independent of other circulating biomarkers, traditional risk score, and non-invasive imaging analyses. C_LI What Are the Clinical Implications?O_LICirculating myosin-11 may serve as a potential biomarker for identifying dysregulation of arterial smooth muscle cells during the progression of atherosclerosis. C_LIO_LIFurther studies are warranted to evaluate whether myosin-11 levels, in combination with other reported biomarkers and risk scores, could aid in stratification of asymptomatic individuals with higher risk of ASCVD. C_LI