GAS6 protein and lipid metabolism dysfunction: a potential biomarker for risk stratification in patients with ischaemic chronic heart failure and metabolic disorders

Аннотация

Chronic heart failure (CHF) remains a critical problem, the relevance of which is growing against the background of cardiometabolic polymorbidity. Comorbid conditions such as type 2 diabetes mellitus (T2DM) and obesity have common pathogenetic mechanisms that accelerate myocardial remodelling and fibrosis. The GAS6 (Growth Arrest-Specific 6) protein, as a ligand for the TAM family of receptors, is a central regulator of inflammation, cell survival, and vascular remodelling. Establishing a link between GAS6 levels and specific lipid metabolism disorders in the context of CHF is critical for improving risk stratification. The aim of the study was to investigate the activity of GAS6 protein and its relationship with lipid metabolism indicators in patients with ischaemic CHF, as well as to determine its potential prognostic value for risk stratification depending on the presence of concomitant metabolic pathology. The study included 225 patients with ischemic CHF and 30 healthy individuals (control group). The patients were divided into 4 groups: Group 1 (n=75) – coronary artery disease (CAD) + T2DM + obesity; Group 2 (n=50) – CAD + T2DM; Group 3 (n=50) – CAD + obesity; Group 4 (n=50) – CAD without metabolic pathology. Lipid metabolism indicators (total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), atherogenicity coefficient (AC)) and serum GAS6 levels (using the ELISA kit Cusabio, USA) were determined. Spearman's rank correlation coefficient was used to determine correlations, with a critical significance level of p<0.05. According to the results of the study, the GAS6 protein content was highest in Group 1 (31.64±18.71 ng/ml), exceeding the control values by 66.3% (p<0.001), which indicates the cumulative effect of combined pathology. GAS6 levels in Group 3 and Group 2 were significantly higher than the control (by 41.8% and 31.1% , respectively). When analysing the correlations in Group 1, strong and significant positive correlations were found between GAS6 and BMI (r=0.68) and proatherogenic lipid metabolism fractions (LDL-C (r=0.54), VLDL-C (r=0.51), TG (r=0.47)). GAS6 is a sensitive marker, the activation of which is closely associated with the number and type of concomitant metabolic disorders. The established strong direct relationship between GAS6 and BMI and pro­athero­genic lipid fractions confirms that this protein is a powerful biochemical mediator that reflects the degree of dyslipidaemia and exacerbates atherosclerosis processes in patients with cardiometabolic polymorbidity. The level of GAS6 can serve as an important diagnostic and prognostic marker for early stratification of patients with ischaemic heart failure.