The predictive value of stromal cell-derived factor-1 (SDF-1) has not been established in patients with non-ST elevation acute coronary syndrome (non-STEACS). A total of 678 consecutive patients with non-STEACS and moderate to high TIMI (Thrombolysis In Myocardial Infarction) risk scores were recruited. All patients underwent an early invasive strategy and then were followed-up for 18 months for clinical events. Left ventricular remodeling was assessed by echocardiography. Plasma concentrations of SDF-1 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were analyzed. SDF-1 level was an independent predictor of left ventricular remodeling (OR = 2.95, 95% CI = 2.02-4.30, P < 0.001). Cox regression analysis demonstrated that both SDF-1 and NT-proBNP levels were significant independent predictors of death, myocardial infarction, or heart failure (HR = 2.45, 95% CI = 1.71-3.50, P < 0.001; HR = 3.71, 95% CI = 2.41-5.70, P < 0.001, respectively). The area under the ROC curves for SDF-1 (0.776) and NT-proBNP (0.817) were similar. The logistic model with both markers yielded a larger area under the ROC curve (0.862) than that of SDF-1 (P < 0.001) or NT-proBNP (P = 0.0001) alone. In patients stratified by NT-proBNP (above 615.4 pmol/L), SDF-1 (above 2175.1 pg/mL) was associated with poorer outcome (P < 0.001). Findings were similar for death and heart failure as individual endpoints. In non-STEACS, higher SDF-1 levels were a significant predictor of death, myocardial infarction, or heart failure independently of baseline clinical characteristics and NT-proBNP, and the combination of SDF-1 and NTproBNP significantly improved risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers in non-ST elevation acute coronary syndrome.
Essential hypertension (EH) is a frequent, chronic, age-related disorder, which remains a major modifiable risk factor for cardiovascular disease despite important advances in our understanding of its pathophysiology. Previous studies have noted a consistent maternal effect on blood pressure (BP). Consequently, mutations in mitochondrial DNA (mtDNA) have become an additional target of investigations on the missing BP heritability. Among these mutations, mt-transfer RNA (tRNA) is a hot mutational spot for pathogenic mutations associated with EH. Mutant mtDNA aggravates mitochondrial dysfunction, pivotally contributing to the clinical phenotype. Moreover, the damaged mitochondria, due to their inability to provide the high-energy requirements for cells, generate reactive oxygen species (ROS) and induce mitochondrial-mediated cell death pathways. Therefore, mitochondrial dysfunction plays a critical role in the pathogenesis of EH. This review summarizes the basic knowledge of mitochondrial genetics and EH-associated mtDNA mutations and further discusses the molecular mechanisms behind these mtDNA mutations in clinical manifestations of EH.
Mutations in mitochondrial DNA (mtDNA) are one of the most important causes of hearing loss. Of these, the homoplasmic A1555G and C1494T mutations at the highly conserved decoding site of the 12S rRNA gene are well documented as being associated with either aminoglycoside-induced or nonsyndromic hearing loss in many families worldwide. Moreover, five mutations associated with nonsyndromic hearing loss have been identified in the tRNA(Ser(UCN)) gene: A7445G, 7472insC, T7505C, T7510C, and T7511C. Other mtDNA mutations associated with deafness are mainly located in tRNA and protein-coding genes. Failures in mitochondrial tRNA metabolism or protein synthesis were observed from cybrid cells harboring these primary mutations, thereby causing the mitochondrial dysfunctions responsible for deafness. This review article provides a detailed summary of mtDNA mutations that have been reported in deafness and further discusses the molecular mechanisms of these mtDNA mutations in deafness expression.
Adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects. This study investigated whether common single nucleotide polymorphisms (SNPs) in the adiponectin gene influenced plasma adiponectin level and whether they were associated with the risk of coronary artery disease (CAD) and its angiographical severity in type 2 diabetes in Chinese population.
Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder presenting a challenge for clinical investigators. To investigate the association of a mitochondrial genetic basis with PCOS, we screened mutations of the whole mitochondrial genome in 57 women patients with PCOS and 38 healthy control individuals. Two-step PCR reactions were adopted to amplify and sequence the whole mitochondrial genome. A 9-bp deletion variant appeared in homoplasmy between PCOS patients and control individuals. In the 62 individuals with complete sequences, eight of 34 (23.5%) patients showed the 9-bp deletion, compared with only two of 28 (7.1%) in healthy controls. The 9-bp deletion variant in region V of mitochondrial DNA may be associated with the heterogeneous disorder PCOS.
According to a recent report by Sunami et al., a maternally inherited Japanese family with variable phenotypes including mitochondrial myopathy, recurrent headache, and myoclonus and epilepsy had been described to be associated with mitochondrial tRNA(Leu(UUR)) 3291T>C mutation. In order to verify this association, we reanalyzed the clinical and molecular datasets obtained from Sunamis work; in addition, a phylogenetic approach was employed to evaluate the conservation index of this mutation among different species. We further utilized RNA Fold Web Server to predict the minimum free energy (MFE) of tRNA(Leu(UUR)) gene with and without this mutation. Most strikingly, a low level of conservation was found regarding 3291T>C mutation and a slight change in MFE had been observed between the wild type and the mutant. Our negative results gave no support for an active role for this mutation on the clinical expression of mitochondrial disorders.
Mutations in mitochondrial DNA are associated with cardiovascular diseases. We reported here molecular characterization of a three-generation Han Chinese family with maternally transmitted hypertension. Most strikingly, this family exhibited a high penetrance of hypertension. Sequence analysis of mitochondrial genome showed the presence of 12,338T>C mutation and 12,330A>G mutation and distinct sets of polymorphisms belonging to the Asian haplogroup F2b. Interestingly, the well-known 12,338T>C mutation, which caused a change of methionine in the translational initiation codon of ND5, also localized in two nucleotides adjacent to the 3 end of tRNA(Leu(CUN)), was implied to cause a decrease in ND5 mRNA level as well as to alter tRNA(Leu(CUN)) stability level. Moreover, the highly conserved 12,330A>G mutation, which disrupted the base pairing (6T-67A) in acceptor arm of tRNA(Leu(CUN)), may result in the failure of tRNA(Leu(CUN)) metabolism. Therefore, the combination of ND5 12,338T>C and tRNA(Leu(CUN)) 12,330A>G mutations may contribute to the high penetrance of hypertension in this Chinese family.
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