In clinical cohort studies, high expression of long-chain acyl-coenzyme A synthetases 1 (ACSL1 gene) in peripheral white blood cells of patients with acute myocardial infarction (AMI) has been utilized as molecular markers of myocardial infarction diagnosis. The plasma triglyceride level of AMI patients is significantly higher than that of healthy individuals. We hypothesized that the high expression of ACSL1 increases the level of triglyceride, which is one of the pathogenesis of AMI promoted by ACSL1. In this report, cell culture based methods were adopted to test the hypothesis and further investigate the effect and mechanism of ACSL1 on lipid metabolism. In this study, liver cells of healthy individuals were cultured, the overexpression and the knockdown vectors of ACSL1 were constructed and transfected into liver cells. The transfection was verified at the mRNA and protein level. Intracellular triglyceride content was quantitatively analyzed using ELISA. Changes of genes related to lipid metabolism were subsequently measured through PCR array. Overexpression of ACSL1 led to higher gene expression and protein levels compared to control and the triglyceride content was significantly increased in overexpressing cells. The expression level of fatty acid oxidation pathway PPARγ was significantly down-regulated compared with the control group, as were genes associated with fatty acid synthesis pathways: SREBP1, ACC, FAS, and SCD1. ACSL1 knockdown decreased the content of triglyceride whereas PPARγ was up-regulated and SREBP1, ACC, FAS, and SCD1 were down-regulated compared with the control group. In summary, high expression of ACSL1 reduced fatty acid β-oxidation through the PPARγ pathway, thereby increasing triglyceride levels.

Background

The current study aimed to investigate whether the increased expression of long chain acyl-coenzymeA synthetase 1 (ACSL1) in peripheral blood leukocytes (PBL) may be a molecular marker for the genetic evaluation of acute myocardial infarction (AMI). The mechanism of action of ACSL1 in the pathogenesis of AMI was also investigated. A total of 75 patients with AMI and 70 individuals without coronary heart disease were selected to participate in the present study. The demographic and clinical information of the enrolled subjects was recorded. Reverse transcription quantitative polymerase chain reaction and western blot analysis were applied to measure the expression of ACSL1 at the mRNA and protein levels. It was demonstrated that the expression of ACSL1 mRNA and protein in PBL was increased in patients with AMI compared with controls. Logistic regression analysis indicated that ACSL1 expression in PBL was an independent risk factor of AMI. There was a significant positive association between the level of ACSL1 expression and the degree of atherosclerosis in the coronary artery. Furthermore, patients with AMI exhibited an increased risk of atherosclerosis due to increased fasting blood glucose, total cholesterol, triglyceride and lipoprotein levels and decreased high-density lipoprotein levels, compared with controls. Therefore, the current study demonstrated that ACSL1 expression was increased in the PBLs of patients with AMI. The elevated expression of ACSL1 acts an independent risk factor of AMI and may act as a potential biomarker when determining the risk of AMI.

No abstract