ABSTRACT
BACKGROUND: N-acetylneuraminic acid (Neu5Ac) is a functional metabolite involved in coronary artery disease (CAD). We aimed to evaluate the relationship between serum Neu5Ac and the risk and prognosis of acute coronary syndrome (ACS) in a real-world prospective study. METHODS: Patients with suspected ACS who underwent coronary angiography were included. Serum Neu5Ac was measured at admission. Coronary lesion severity was evaluated by Gensini Score. GRACE risk stratification was performed at admission. Major adverse cardiac events (MACEs) were recorded during follow-up. RESULTS: A total of 766 patients, including 537 with unstable angina (UAP), 100 with myocardial infarction (MI), and 129 without CAD were included. The circulating Neu5Ac level was significantly higher in patients with MI (median [1QR]: 297[220, 374] ng/ml) than in those with UAP (227 [114, 312] ng/ml) or without CAD (207 [114, 276] ng/ml; both p < 0.001). Serum level of Neu5Ac was positively correlated with age, hypertension, serum uric acid, creatinine, MB isoform of creatine kinase (CK-MB), and Gensini score (all p < 0.05). Receiver operating characteristic curve analysis showed that a higher serum Neu5Ac was potentially associated with MI and high-risk GRACE stratification in ACS patients. Logistic analysis identified only elevated serum Neu5Ac as an independent predictor of MACEs in these patients (odds ratio [OR]: 1.003, 95% confidence interval [CI]: 1.002-1.005, p < 0.001). CONCLUSIONS: Serum Neu5Ac is associated with myocardial injury, GRACE risk category, and prognosis in ACS patients.
Subject(s)
Acute Coronary Syndrome/blood , N-Acetylneuraminic Acid/blood , Acute Coronary Syndrome/diagnostic imaging , Aged , Biomarkers/blood , Coronary Angiography , Female , Humans , Male , Middle Aged , Patient Admission , Prognosis , Prospective Studies , Risk Assessment , Risk Factors , Time Factors , Up-RegulationABSTRACT
MicroRNA (miR)138 serves an important role in the proliferation, differentiation and apoptosis of human pulmonary artery smooth muscle cells (HPASMCs), indi-cating the involvement of miR138 in the development and progression of pulmonary artery hypertension (PAH). Potassium channel subfamily K member 3 (TASK1), a twopore domain K+ channel, is expressed in HPASMCs and is associated with hypoxic PAH. However, whether miR138 mediates PAH through targeting TASK1 is not known. In the present study, HPASMCs were transfected with miR138 mimic to establish a PAH model in vitro, and the effects of a miR138 inhibitor and a TASK1 inhibitor (A293) were examined. Cell proliferation and mitochondrial membrane potential (MMP) were measured by CCK8 assay and flow cytometry, respectively. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to examine the expression of miR138, TASK1, Bcl2, caspase3 and activation of extracellular signalregulated kinase 1/2 (ERK1/2). A dualluciferase reporter assay was also used to analyse the expression level of TASK1 in HPASMCs. The results of the present study demonstrated that the miR138 mimic promoted proliferation and MMP level, which was similar to the effect of A293 treatment on HPASMCs. However, the miR138 inhibitor inhibited the effects induced by miR138 mimic or A293 treatment, as demonstrated by a decrease in proliferation and MMP level in HPASMCs, accompanied by a decrease of Bcl2 and an increase of caspase3 expression levels, as well as ERK1/2 activation. The dualluciferase reporter assay indicated that TASK1 expression was negatively regulated by miR138. The results of the present study suggested that miR138 promoted proliferation and suppressed mitochondrial depolarization of HPASMCs by targeting TASK1.
Subject(s)
Cell Proliferation , Membrane Potential, Mitochondrial , MicroRNAs/genetics , Myocytes, Smooth Muscle/cytology , Nerve Tissue Proteins/genetics , Potassium Channels, Tandem Pore Domain/genetics , Pulmonary Artery/cytology , Aged , Cells, Cultured , Female , Gene Expression Regulation , Humans , MAP Kinase Signaling System , Male , Middle Aged , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Pulmonary Artery/metabolismABSTRACT
The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, circulating levels of homocysteine (Hcy), and the severity of coronary lesion in patients with acute coronary syndrome (ACS) remains unknown.Consecutive ACS patients were included. MTHFR C677T polymorphisms were determined via amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Gensini scores were used to evaluate the severity of coronary lesions.Three hundred ten ACS patients were included, and grouped according to the MTHFR C677T polymorphism variant: CC (nâ=â78, 25.2%), CT (nâ=â137, 44.2%), and TT (nâ=â95, 30.6%) groups. No significant differences were detected with respect to baseline characteristics. Patients in TT group had significantly higher Hcy, and significantly lower folic acid (FA) levels as compared with those in the other 2 groups (Pâ<â.05 for both). More importantly, patients with TT had more severe coronary lesions as compared with those from the other 2 groups, as evidenced by higher Gensini scores (Pâ<â.05 for both); however, no significant differences were observed with respect to the numbers of affected coronary arteries, or the number, length, and diameter of stents implanted in each group (Pâ>â.05 for all). On multivariate logistic regression analysis, presence of a T allele in MTHFR C677T was found to be independently associated with higher circulating Hcy (odds ratio [OR]â=â1.06, 95% confidence interval [CI]: 1.01-1.12, Pâ=â.024), and higher Gensini scores (OR: 1.01, 95% CI: 1.00-1.02, Pâ=â.046).MTHFR C677T TT polymorphism was associated with higher Hcy levels and more severe coronary lesions in patients with ACS.