High expression of long chain acyl‑coenzyme A synthetaseï¿½1 in peripheral blood may be a molecular marker for assessing the risk of acute myocardial infarction

Yang, Liping; Yang, Yan; Si, Daoyuan; Shi, Kaiyao; Liu, Dongna; Meng, Heyu; Meng, F.

doi:10.3892/etm.2017.5091

Cited by 17 publications

(21 citation statements)

References 35 publications

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“…The expression of ACSL1 is significantly related to the degree of atherosclerosis in the coronary artery (39). it has been observed that acSl1 is upregulated in peripheral blood leukocytes of patients with acute Mi (39). The present study further demonstrated the important roles of hsa-mir-142-3p and acSl1 in Mi.…”

Section: Discussionsupporting

confidence: 74%

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Uncovering potential differentially expressed miRNAs and targeted mRNAs in myocardial infarction based on integrating analysis

Wang¹,

Cao²

2020

Mol Med Rep

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Myocardial infarction (Mi) is one of the leading causes of death globally. The aim of the present study was to find valuable micrornas (mirnas/mirs) and target mrnas in order to contribute to our understanding of the pathology of Mi. mirna and mrna data were downloaded for differential expression analysis. Then, a regulatory network between mirnas and mrnas was established, followed by function annotation of target mrnas. Thirdly, prognosis and diagnostic analysis of differentially methylated target mrnas were performed. Finally, an in vitro experiment was used to validate the expression of selected mirnas and target mrnas. a total of 19 differentially expressed mirnas and 1,007 differentially expressed mRNAs were identified. Several regulatory interaction pairs between mirna and mrnas were identified, such as hsa-mir-142-2p-long-chain-fattyacid-coa ligase 1 (acSl1), hsa-mir-15a-3p-nicotinamide phosphoribosyltransferase (naMPT), hsa-mir-33b-5p-regulator of G-protein signaling 2 (rGS2), hsa-mir-17-3p-Jun dimerization protein 2 (JdP2), hsa-mir-24-1-5p-aquaporin-9 (aQP9) and hsa-mir-34a-5p-STaT1/aKT3. of note, it was demonstrated that acSl1, naMPT, rGS2, JdP2, aQP9, STaT1 and aKT3 had diagnostic and prognostic values for patients with Mi. in addition, STaT1 was involved in the 'chemokine signaling pathway' and 'Jak-STaT signaling pathway'. aKT3 was involved in both the 'MaPK signaling pathway' and 'T cell receptor signaling pathway'. reverse transcription-quantitative Pcr validation of hsa-mir-142-3p, hsa-mir-15a-3p, hsa-mir-33b-5p, acSl1, naMPT, rGS2 and JdP2 expression was consistent with the bioinformatics analysis. In conclusion, the identified miRNAs and mRNAs may be involved in the pathology of Mi.

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Section: Discussionsupporting

confidence: 74%

“…overexpression of acSl1 can lead to severe cardiomyopathy (38). The expression of ACSL1 is significantly related to the degree of atherosclerosis in the coronary artery (39). it has been observed that acSl1 is upregulated in peripheral blood leukocytes of patients with acute Mi (39).…”

Section: Discussionmentioning

confidence: 99%

Uncovering potential differentially expressed miRNAs and targeted mRNAs in myocardial infarction based on integrating analysis

Wang¹,

Cao²

2020

Mol Med Rep

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“…The high expression of ACSL1 was an independent risk factor for AMI. The triglycerides content in peripheral white blood cells of patients with myocardial infarction was shown to increase [4]. Therefore, the high expression of ACSL1 gene increased the level of triglyceride, which has been hypothesized to be one of the pathogenesis of AMI promoted by ACSL1.…”

Section: Introductionmentioning

confidence: 99%

“…The levels of total cholesterol, plasma triglyceride and plasma low-density lipoprotein (LDL) of AMI patients are significantly higher than those of healthy individuals. The results of our previous gene chip study suggested that the expression of ACSL1 in peripheral white blood cells (PBL) of AMI patients and healthy controls groups significantly increased (LogFC=2.590, P=0.04) [4]. The long-chain acyl-coenzyme A synthetases (ACSL) family played a key role in regulating fatty acids Ivyspring International Publisher which entered the synthetic or oxidative pathways [5].…”

Section: Introductionmentioning

confidence: 99%

ACSL1 affects Triglyceride Levels through the PPARγ Pathway

Li¹,

Li²,

Meng³

et al. 2020

Int. J. Med. Sci.

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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.

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“…The gene was associated with concentration of IDL particles in this study ( p = 1.82 × 10 −7 ), and its deficiency in the liver has been shown to reduce synthesis of triglycerides and beta oxidation, and alter the fatty acid composition of major phospholipids [37]. An intronic variant (rs60780116) in ACSL1 has been associated with T2D [38] and elevated expression of ACSL1 has been shown to be an independent risk factor for acute myocardial infarction [39].…”

Section: Discussionmentioning

confidence: 90%

The influence of rare variants in circulating metabolic biomarkers

Riveros-Mckay

Oliver‐Williams

Karthikeyan

et al. 2018

Preprint

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Circulating metabolite levels are biomarkers for cardiovascular disease (CVD). We tested association between rare sequence variants and 226 serum lipoproteins, lipids and amino acids in 7,142 healthy participants. Gene-based association analyses identified novel gene-trait associations with ACSL1, MYCN, FBXO36 and B4GALNT3 (p<2.5 × 10−6), and confirmed established associations. Regulation of the pyruvate dehydrogenase (PDH) complex was associated for the first time, in gene set analyses, with IDL and LDL parameters, as well as circulating cholesterol (pMETASKAT <2.41 × 10−6). Individuals at the lower tails of the distributions of four out of 49 lipoproteins and lipids had an excess of predicted deleterious variants in lipoprotein disorder and metabolism gene sets (ppermutation<0.00037). These four traits were CVD risk factors (e.g. S-VLDL-C), demonstrating that rare “protective” variation is a significant contributor to lipoprotein levels in a healthy population. In conclusion, rare variant analysis of these important metabolic biomarkers reveals novel loci and pathways involved in their regulation.

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High expression of long chain acyl‑coenzyme A synthetaseï¿½1 in peripheral blood may be a molecular marker for assessing the risk of acute myocardial infarction

Cited by 17 publications

References 35 publications

Uncovering potential differentially expressed miRNAs and targeted mRNAs in myocardial infarction based on integrating analysis

Uncovering potential differentially expressed miRNAs and targeted mRNAs in myocardial infarction based on integrating analysis

ACSL1 affects Triglyceride Levels through the PPARγ Pathway

The influence of rare variants in circulating metabolic biomarkers

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