Lin Mi

Mitofusin 2 Inhibits Angiotensin II-Induced Myocardial Hypertrophy

Background and Objectives: Myocardial hypertrophy is a common clinical finding leading to heart failure and sudden death. Mitofusin 2 (Mfn2), a hyperplasia suppressor protein, is downregulated in hypertrophic heart. This study examined the role of Mfn2 in myocardial hypertrophy and its potential signal pathway. Methods and Results: In in vitro studies, neonatal cardiac myocytes were isolated and cultured. Incubation of cultured cardiomycytes with angiotensin II (Ang II) inhibited gene expression of Mfn2; induced cell hypertrophy and protein synthesis; and activated protein kinase Akt. Pretreatment of cells with AdMfn2—a replication-deficient adenoviral vector encoding rat Mfn2 gene—upregulated Mfn2 expression and subsequently attenuated Ang II-induced cell hypertrophy; protein synthesis; and Akt activation. In in vivo studies, direct gene delivery of AdMfn2 into myocardium decreased the infusion of Ang II-induced atrial natriuretic factor (ANF, a hypertrophic marker) expression and cardiomyocyte cross-sectional area. Consistently, upregulation of Mfn2 in myocardium decreased the thicknesses of anterior and posterior walls of left ventricle (LV) and the ratio of LV mass/body weight in Ang II-treated rats. Of note, AdGFP (control for AdMfn2) did not affect the effects of Ang II in vitro or in vivo. Conclusions: Upregulation of Mfn2 inhibits Ang II-induced myocardial hypertrophy. In this process, inhibition of Akt activation seems to play a significant role. These findings indicate Mfn2 is a critical protein in modulating myocyte hypertrophy.

Growth differentiation factor 15 in different stages of heart failure: potential screening implications

Identification of individuals in the early stage of heart failure (HF) may allow earlier initiation of disease-modifying treatment. We evaluated concentrations of the growth differentiation factor (GDF)-15at different stages and its potential screening value in 208 subjects. Plasma GDF-15 was measured by using an enzyme-linked immunosorbent assay. GDF-15 was positively correlated with the stages of HF (r=0.804, p<0.001). In distinguishing patients with stage B HF, the area under the curve was 0.873 (p<0.001). These findings indicate that GDF-15 concentration was elevated with the progressing stages of HFand might have potential screening implications for stage B HF.

Dramatic changes in catestatin are associated with hemodynamics in acute myocardial infarction.

Acute myocardial infarction (AMI) is characterized by complex neuroendocrine activation. To investigate catestatin profiles, serial catestatin levels were determined by enzyme-linked immunosorbent assay in the first week after AMI in 50 patients. Catestatin levels reduced at admission and negatively correlated with heart rates; it increased significantly on the third day but remained decreased at 1 week and positively with blood pressure. In a subgroup of 20 patients admitted within 4 h after onset, circulating catestatin correlated inversely with norepinephrine. Catestatin might be involved in the course of AMI and act as a tool in monitoring the progression of AMI.

Catestatin is useful in detecting patients with stage B heart failure

Screening patients with stage B heart failure(HF) may be one strategy for reducing human morbidity. To describe catestatin levels in different stages of HF and evaluate the diagnostic utility of catestatin for detecting stage B HF, we included 300 patients. Catestatin, BNP testing and echocardiogram were performed. Our studies showed catestatin decreased gradually from stage A to C. There was significant difference between stage A and B. Cutoff value for detecting stage B HF was 19.73 ng/ml for catestatin with 90% sensitivity and 50.9% specificity. These results may have implications in the new method to detect patients with stage B HF.

Effects of atorvastatin loading prior to primary percutaneous coronary intervention on endothelial function and inflammatory factors in patients with ST-segment elevation myocardial infarction

Previous studies have demonstrated the beneficial effect of statin loading prior to elective and early percutaneous coronary intervention (PCI), in which the ‘pleiotropic effects’ of statins may contribute to these clinical benefits. The aim of the present study was to examine the potential effects of atorvastatin loading prior to primary PCI on coronary endothelial function and inflammatory factors in patients with acute ST-segment elevation myocardial infarction (STEMI). A total of 60 patients with STEMI were randomized into three groups: Loading dose (80 mg atorvastatin prior to PCI; n=20), regular dose (20 mg atorvastatin prior to PCI; n=20) and control (without atorvastatin prior to PCI; n=20). The plasma samples were collected prior to, and immediately, 6 and 24 h after PCI in all the patients. The plasma concentrations of endothelial nitric oxide synthase (eNOS), nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) were examined using ELISA. The plasma eNOS levels immediately and 24 h after PCI were significantly higher in the regular dose group compared with the other groups. However, there were no significant differences in the plasma eNOS concentration prior to and 6 h after PCI, or in the plasma NO concentration at any of the time-points among the three groups. The plasma IL-6 levels prior to PCI were significantly lower in the loading dose group compared with the other groups; however, there were no significant differences in the plasma concentration of IL-6 following PCI or in the concentrations of TNF-α and ICAM-1 at any of the time-points among the three groups. In conclusion, atorvastatin loading in patients with STEMI undergoing primary PCI may not have protective effects on endothelial function and the inflammatory reaction.

Changes and significance of serum angiopoietin-2 levels in patients with coronary heart disease

Coronary heart disease (CHD) is characterized by inflammatory process and endothelial dysfunction. To investigate angiopoietin-2 (Ang-2) profiles, we evaluated serum Ang-2 levels in different types of CHD in 166 subjects. Ang-2 was measured by enzyme-linked immunosorbent assay. Serum Ang-2 levels were significantly elevated in patients with CHD and gradually increased with advance of CHD. Ang-2 was positively correlated with Gensini scores and hs-CRP. Ang-2 might have potential implication in detecting and monitoring the progression of CHD.

Dynamic changes in serum angiopoietin-1, angiopoietin-2, and angiopoietin-2/angiopoietin-1 ratio in acute myocardial infarction patients treated with primary percutaneous coronary intervention

Context: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) play divergent roles in myocardial ischemia and reperfusion injury. Objective: To investigate serum Ang-1 and Ang-2 levels in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods: Serum Ang-1 and Ang-2 were measured in 85 STEMI patients in the first week after PCI. Results: Ang-1, Ang-2 and Ang-2/Ang-1 ratio (Ang-2/1) were all increased at admission, and had dynamic changes after PCI. Ang-2 and Ang-2/1 at admission and 2 h after PCI were positively correlated with peak cardiac troponin T levels. Conclusion: The extent of myocardial damage may be linked to circulating Ang-2 and Ang-2/1.

Serum erythropoietin: a useful biomarker for coronary collateral development and potential target for therapeutic angiogenesis among the patients with coronary chronic total occlusion

Abstract The study was to investigate the association of endogenous erythropoietin (EPO) and coronary collateral development. Forty-nine patients (31 with chronic total occlusion (CTO), 18 with normal coronary artery) were consecutively enrolled. The serum EPO was positively related with Rentrop class. Increased serum EPO was one of the independent predictors of good collateral development (odds ratio 1.31; p = 0.025). A significantly positive correlation was seen between serum EPO and vascular endothelial growth factor (VEGF) levels (r = 0.96, p < 0.001). Circulatory EPO may be a useful biomarker for coronary collateral development and potential target for therapeutic angiogenesis in patients with CTO.

An analysis of patients receiving emergency CAG without PCI and the value of GRACE score in predicting PCI possibilities in NSTE-ACS patients.

Background There are patients who underwent emergency coronary angiography (CAG) but did not receive percutaneous coronary intervention (PCI). The aim of this study was to analyze these reasons. Methods This is a single-center retrospective study. We recruited 201 consecutive patients who received emergency CAG but did not receive PCI. To investigate the value of the Global Registry of Acute Coronary Events (GRACE) score in predicting PCI possibilities in non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients, we recruited 80 consecutive patients who presented with NSTE-ACS and received emergency CAG as well as emergency PCI. Results Among the 201 patients who received emergency CAG but did not receive PCI, 26% patients had final diagnosis other than coronary heart disease. In the patients with significant coronary artery stenosis, 23 patients (11.5%) were recommended to coronary artery bypass grafting (CABG), one patient (0.5%) refused PCI; 13 patients (6.5%) with significant thrombus burden were treated with glycoprotein IIb/IIIa receptor antagonist; 74 patients (36.8%) were treated with drug therapy because no severe stenosis (> 70%) was present in the crime vessel. Moreover, 80 of the 201 patients were presented with NSTE-ACS (excluding those patients with final diagnosis other than coronary heart disease, excluding those patients planned for CABG treatment), referred as non PCI NSTE-ACS. When comparing their GRACE scores with 80 consecutive patients presented with NSTE-ACS who received emergency CAG as well as emergency PCI (referred as PCI NSTE-ACS), we found that PCI NSTE-ACS patients had significantly higher GRACE scores compared with non PCI NSTE-ACS patients. We then used Receiver Operator Characteristic Curve (ROC) to test whether the GRACE score is good at evaluating the possibilities of PCI in NSTE-ACS patients. The area under the curve was 0.854 ± 0.030 (P < 0.001), indicating good predictive value. Furthermore, we analyzed results derived from ROC statistics, and found that a GRACE score of 125.5, as a cut-off, has high sensitivity and specificity in evaluating PCI possibilities in NSTE-ACS patients. Conclusions Our findings indicate that the GRACE score has predictive value in determining whether NSTE-ACS patients would receive PCI.

Correlation between growth differentiation factor-15 and collagen metabolism indicators in patients with myocardial infarction and heart failure

Background Growth differentiation factor (GDF)-15, a divergent member of the transforming growth factor beta super-family does appear to be up-regulated in response to experimental pressure overload and progression of heart failure (HF). HF frequently develops after myocardial infarction (MI), contributing to worse outcome. The aim of this study is to assess the correlation between GDF-15 levels and markers related to collagen turnover in different stages of HF. Methods The study consists of a cohort of 179 patients, including stable angina pectoris patients (AP group, n = 50), old MI patients without HF (OMI group, n = 56), old MI patients with HF (OMI-HF group, n = 38) and normal Control group (n = 35). Both indicators reflecting the synthesis and degradation rates of collagen including precollagen I N-terminal peptide (PINP), type I collagen carboxy-terminal peptide (ICTP), precollagen III N-terminal peptide (PIIINP) and GDF-15 were measured using an enzyme-linked inmunosorbent assay. Results The plasma GDF-15 level was higher in OMI-HF group (1373.4 ± 275.4 ng/L) than OMI group (1036.1 ± 248.6 ng/L), AP group (784.6 ± 222.4 ng/L) and Control group (483.8 ± 186.4 ng/L) (P < 0.001). The indicators of collagen turnover (ICTP, PINP, PIIINP) all increased in the OMI-HF group compared with Control group (3.03 ± 1.02 µg/L vs. 2.08 ± 0.95 µg/L, 22.2 ± 6.6 µg/L vs. 16.7 ± 5.1 µg/L and 13.2 ± 7.9 µg/L vs. 6.4 ± 2.1 µg/L, respectively; P < 0.01). GDF-15 positively correlated with ICTP and PIIINP (r = 0.302, P < 0.001 and r = 0.206, P = 0.006, respectively). GDF-15 positively correlated to the echocardiographic diastolic indicators E/Em and left atrial pressure (r = 0.349 and r = 0.358, respectively; P < 0.01), and inversely correlated to the systolic indicators left ventricular ejection fraction and the average of peak systolic myocardial velocities (Sm) (r = −0.623 and r = −0.365, respectively; P < 0.01). Conclusion Plasma GDF-15 is associated with the indicators of type I and III collagen turnover.