CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 2, May/June 2023 104 AFRICA Circulatory soluble LOX-1 is a novel predictor for coronary artery disease patients Md Sayed Ali Sheikh Abstract Objective: This study investigated the biomarker effect of soluble lectin-like oxidised low-density lipoprotein (sLOX-1) levels for the evaluation of stable and unstable coronary heart disease, correlating it with aging. Methods: This case–control study was conducted at the Cardiology Department of Xiangya Hospital between June 2015 and September 2018. Stable coronary artery disease (CAD) patients were confirmed by an invasive coronary angiogram, and American College of Cardiology as well as European Cardiology Society clinical protocols were used for the diagnosis of unstable CAD subjects. Plasma sLOX1 levels were determined from 226 stable CAD patients, 138 unstable CAD subjects and 75 healthy participants by enzyme-linked immunosorbent assay. Results: Plasma sLOX-1 expressions were significantly elevated in stable CAD patients (4.5-fold) and unstable CAD patients (5.8-fold) above that of volunteer healthy participants. Moreover, between the stable and unstable patient groups, sLOX-1 concentrations were also statistically significantly different (p < 0.001). Levels of plasma sLOX-1 in the healthy female (30–60 years), and stable and unstable CAD female subjects (61–84 years) were markedly elevated compared with healthy male (30–60 years), as well as stable and unstable CAD male patients (61–84 years) (p < 0.001). Besides, in the female unstable CAD (61–84 years) subjects, circulatory sLOX-1 expressions were much higher than in the younger female unstable CAD (30–60 years) patients (p < 0.001). The stable CAD patients were clearly differentiated from healthy subjects with a high sensitivity of the area under the curve (AUC = 0.895). Unstable CAD patients and healthy subjects were also markedly different with a high sensitivity, as shown by AUC (0.902). Stable and unstable CAD subjects were differentiated with an AUC of 0.867. Conclusion: Elevated plasma sLOX-1 levels could be regarded as a novel biomarker for detecting CAD patients and there was a significant association with gender and aging. Keywords: coronary artery disease, soluble LOX-1, biomarker, aging Submitted 4/12/20, accepted 2/7/22 Published online 11/10/22 Cardiovasc J Afr 2023; 34: 104–108 www.cvja.co.za DOI: 10.5830/CVJA-2022-038 Globally, ischaemic cardiac disease is the principal cause of early mortality in all ethnic groups, both male and female. Formation of a stable atherosclerotic plaque and subsequent rupture within the coronary arteries are usually considered as stable and unstable coronary heart disease, respectively. In one study, early assessment with proper management of a coronary artery disease (CAD) patient significantly improved clinical outcome and markedly decreased the incidence of sudden cardiac arrest and mortality rate.1 One in 10 elderly people (80 years old) usually visit a primary care centre or hospital for evaluation of stable chest pain. Due to the increasing complexity of atherosclerotic clinical– pathological correlations, the diagnostic approach for CAD has been divergent. Electrocardiogram (ECG), stress ECG, echocardiography and computed tomography (CT) angiograms are very helpful techniques for early evaluation of coronary heart disease. Moreover, the clinically invasive coronary angiogram is considered a gold-standard method for diagnosis of CAD patients but it has several limitations. Therefore, the discovery of an ideal non-invasive biomarker for early diagnosis of CAD patients is required by the clinician.2 Initiation and progression of atherosclerosis is a crucial mechanism for the development of CAD. Several researchers have demonstrated that the atherosclerotic process is directly linked with alterations of the lectin-like oxidised low-density lipoprotein (ox-LDL) receptor-1 (LOX-1) expressions.3 LOX-1 is a type of E receptor first recognised in endothelial cells and considered as the main mediator for ox-LDL. In endothelial cells, ox-LDL, through the LOX-1 receptor, enhances white blood cell (WBC) adhesion substances and activates caspase-3 pathways, up-regulating reactive oxygen species (ROS) production, and significantly damages endothelial function. Besides, ox-LDL induces LOX-1 expression at the plasma membrane. Moreover, LOX-1 is also expressed from activated macrophages, monocytes, cardiac tissue, platelets, fibroblasts and vascular smooth muscle, and subsequently causes vascular inflammation and the formation of atherosclerotic plaque, as well as erosion and rupture, resulting in thrombus generation and occlusion of the coronary artery.4,5 In one study, the ox-LDL receptor-1 (OLR-1) gene polymorphism significantly increased coronary heart disease risk, especially familial hypercholesterolaemia.6 Besides, the expression of LOX-1 is mainly induced through many inflammatory cytokines, haemodynamic stimuli andmicrovascular dysfunction, and plays an important role in stable CAD and acute myocardial infarction.7,8 Soluble LOX-1 (sLOX-1) molecules released from the cell surface enter into the bloodstream through enzymatic break down of the extracellular proximal membrane domain. Circulatory sLOX-1 levels were up-regulated in obesity, the metabolic syndrome, hyperlipidaemia, hypertension and type 2 diabetes mellitus patients.9,10 Moreover, sLOX‐1 levels were also noticeably up-regulated in severe intracranial artery stenosis Department of Internal Medicine, College of Medicine, Jouf University, Sakaka, Aljouf, Kingdom of Saudi Arabia Md Sayed Ali Sheikh, MB BS, MD, PhD, dshekh@ju.edu.sa, drsheikh07@hotmail.com
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