Background: Coronary artery diseases are the most important cause of premature death, and these diseases are predominantly related to atherosclerosis. Soluble lectin-like oxidized low-density lipoprotein receptor-1 and microRNAs are closely associated with atherosclerotic coronary heart diseases.Aims: To investigate the relationship between the severity and risk of coronary artery disease and plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 and miR-98.Study Design: Case-control study.Methods: Angiographically documented patients with 38 single-vessel, 75 double-vessel, and 62 multi-vessel coronary artery disease; 62 healthy control participants; and 24-hour hypoxic (1% oxygen) human umbilical vein endothelial cells were included in this study. Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 concentrations were determined through enzyme-linked immunosorbent assays, and miR-98 expressions were measured by quantitative real-time polymerase chain reaction.Results: The expressions of plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 levels were progressively and significantly higher in patients with single-vessel, double-vessel, and multi-vessel coronary artery disease than in healthy controls (p<0.001). Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 concentrations in female patients with multi-vessel, double-vessel, and single-vessel coronary artery disease had evidently elevated compared with that in male patients (p<0.001). Plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 levels were remarkably increased in females with coronary artery disease in different age groups compared with the males in the same age groups (p<0.001). Patients with single-vessel (areas under the curve=0.879), double-vessel (area under the curve=0.928), and multi-vessel (area under the curve=0.943) coronary artery disease have been clearly differentiated from healthy participants with respect to high sensitivity and specificity. The expression of miR-98 was noticeably downregulated in patients with single-, double- and multi-vessel occluded coronary artery disease and in hypoxic human umbilical vein endothelial cell compared with controls (p<0.001). Significantly elevated lectin-like oxidized low-density lipoprotein receptor-1 and caspase-3 activity and remarkably decreased cellular viability in hypoxic injured human umbilical vein endothelial cell. On the contrary, mimic of miR-98 markedly reduced caspase-3 and lectin-like oxidized low-density lipoprotein receptor-1 levels and highly increased cellular viability.Conclusion: Elevated circulating plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 levels have a potential impact to identify the severity of coronary artery disease and have a strong correlation with aging as well as the female gender. Reduced plasma miR-98 level is possibly considered a risk factor for coronary artery disease, and agomiR-98 prevents atherosclerosis and cellular injury by targeting lectin-like oxidized low-density lipoprotein receptor-1.