MiR-144-5p/CCL12 Signaling Axis Modulates Ischemic Preconditioning-Mediated Cardio-protection by Reducing Cell Viability, Enhancing Cell Apoptosis, Fibrosis, and Pyroptosis.

Ischemic postconditioning (IPost) represents short periods of nonlethal ischemia-reperfusion performed at the onset of reperfusion. Studies have shown that IPost involves various biological processes such as cell proliferation, apoptosis, and pyroptosis and can activate complex signaling pathways. CCL12 is a critical mediator in the inflammatory process after tissue injury. In the present study, we examined the potential actions of CCL12-mediated signaling pathways in cardioprotection after IPost using a cardiomyocyte model. By applying the bioinformatics analysis, we found that CCL12 was upregulated in the rat heart tissues after I/R injury, and the expression level of CCL12 was restored in rats with IPost. The in vitro studies showed that CCL12 and CCR2 expression levels were upregulated in the hypoxia/reoxygenation (H/R)-induced H9C2 cells, which was attenuated in the H/R + hypoxia post-conditioning (PostC) group. The functional assays showed that H/R treatment reduced cell viability, increased cell apoptosis, and promoted fibrosis and pyroptosis of H9C2 cells, which was attenuated in the H/R + PostC group. Overexpression of CCL12 impaired the protective action of hypoxia post-conditioning in the H9C2 cells. Further mechanistic studies showed that miR-144-5p could directly target the 3' untranslated region of CCL12. Overexpression of miR-144-5p markedly repressed the expression levels of CCL12 and CCR2 in H9C2 cells, while miR-144-5p inhibition had the opposite effects. Furthermore, the inhibition of miR-144-5p reduced the cell viability, increased cell apoptosis, and enhanced fibrosis and pyroptosis of H9C2 cells after H/R or H/R + PostC treatment. In conclusion, CCL12 was downregulated in cardiomyocytes following ischemic postconditioning, and CCL12 overexpression impaired the cardioprotective actions of ischemic postconditioning by reducing cell viability, enhancing cell apoptosis, fibrosis, and pyroptosis. Further mechanistic evidence revealed that CCL12 was a direct target of miR-144-5p, and miR-144-5p/CCL12/CCR2 signaling may represent a critical pathway in mediating the cardioprotective effects of ischemic postconditioning.

Catheter ablation for paroxysmal and persistent atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in cardiovascular departments. Treatments include medical interventions and catheter ablation. Due to uncertainties in medical therapies for AF, and the need to continue sinus rhythm, ablation has been recently considered as a viable alternative. Many new ablation methods based on pulmonary vein isolation (PVI) have been developed. OBJECTIVES: The primary objective of this review was to assess the beneficial and harmful effects of catheter ablation (CA) in comparison with medical treatment in patients with paroxysmal and persistent AF. The secondary objective was to determine the best regimen of CA. SEARCH METHODS: Searches were run on The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 3 2009, MEDLINE (1950 to August 2009), EMBASE (1980 to August 2009), the Chinese Biomedical Literature Database (1978 to August 2009) and the CKNI Chinese Paper Database (1994 to 2009) . Several journals published in Chinese were also handsearched. SELECTION CRITERIA: Randomised controlled trials (RCTs) in people with paroxysmal and persistent AF treated by any type of CA method. Two reviewers independently selected the trials for inclusion. DATA COLLECTION AND ANALYSIS: Assessments of risk of bias were performed by two reviewers, and relative risk (RR) and 95% confidence intervals (CI) were used for dichotomous variables. Meta-analysis were performed where appropriate. MAIN RESULTS: A total of 32 RCTs (3,560 patients) were included. RCTs were small in size and of poor quality.CA compared with medical therapies: seven RCTs indicated that CA had a better effect in inhibiting recurrence of AF [RR 0.27; 95% CI 0.18, 0.41)] but there was significant heterogeneity. There was limited evidence to suggest that sinus rhythm was restored during CA (one small trial: RR 0.28, 95% CI 0.20-0.40), and at the end of follow-up (RR 1.87, 95% CI 1.31-2.67; I(2)=83%). There were no differences in mortality (RR, 0.50, 95% CI 0.04 to 5.65), fatal and non-fatal embolic complication (RR 1.01, 95% CI 0.18 to 5.68) or death from thrombo-embolic events (RR 3.04, 95% CI 0.13 to 73.43).Comparisons of different CAs; 25 RCTs compared CA of various kinds. Circumferential pulmonary vein ablation was better than segmental pulmonary vein ablation in improving symptoms of AF (p<=0.01) and in reducing the recurrence of AF (p<0.01). There is limited evidence to suggest which ablation method was the best. AUTHORS' CONCLUSIONS: There is limited evidence to suggest that CA may be a better treatment option compared to medical therapies in the management of persistent AF. This review was also unable to recommend the best CA method.

Research on clinical characteristics and prognostic analysis of heparin-induced thrombocytopenia after surgery for acute type a aortic dissection.

PURPOSE: The present study aimed to explore the clinical characteristics of heparin-induced thrombocytopenia (HIT) after surgery for acute type A aortic dissection and perform a relevant prognostic analysis. METHODS: After continuous observation and analysis of 204 patients who underwent acute type A aortic dissection, we found that blood platelets decreased significantly after surgery and that these patients can be suspected to suffer HIT based on relevant 4Ts scores. For these suspected HIT patients, a latex particle-enhanced immunoturbidimetric assay was conducted to detect heparin-induced antibodies. Perioperative clinical data of patients in HIT and non-HIT groups were recorded as were blood platelet counts, HIT antibody test results, 4Ts scores, thromboembolic complications, clinical prognosis and outcomes. RESULTS: In the present study, 38 suspected HIT patients, 16 HIT patients and 188 non-HIT patients were selected in the clinical setting. Among them, HIT patients were found to have prolonged cardiopulmonary bypass time (223 min on average vs. 164 min) and delayed aortic cross-clamp time (128 min on average vs. 107 min), and these differences between HIT patients and non-HIT patients were significant (P < 0.05). Additionally, the HIT group required longer operation time and higher dose of heparin, but showing no statistical differences (P > 0.05). The transfusions of blood platelets in the HIT group and non-HIT group were 18.7 ± 5.0u and 15.6 ± 7.34 u, respectively. In the HIT group, the mechanic ventilation time and the length of ICU stay were longer comparing the non-HIT group(P < 0.05), though no significant differences in total length of stay or In-hospital mortality were observed (P > 0.05). The incidence of continuous renal replacement therapy in HIT group was higher than the non-HIT group (P < 0.05). Additionally,there were no significant differences in 24-h postoperative drainage or reoperation for bleeding in both group(P > 0.05). However, the HIT antibody titer in the HIT group was significantly higher than that in the Suspected HIT group (2.7 ± 0.8 U/mL vs. 0.3 ± 0.2 U/mL) (P < 0.05). Among patients diagnosed with HIT, the incidence of thromboembolism reached 31.5%.For example, two HIT patients newly developed thromboembolism in both lower extremities,and three patients experienced cerebral infarction. CONCLUSIONS: After surgery for acute type A aortic dissection, HIT patients developed postoperative complications, the duration of ventilatory support and length of ICU stay were extended, and the incidence of thromboembolism increased. HIT antibody detection and risk classification should be implemented for high-risk patients showing early clinical characteristics.

[Acidic fibroblast growth factor promotes the growth of skeletal muscle satellite cells: experiment with rabbits].

OBJECTIVE: To explore if human recombinant acidic fibroblast growth factor (rhaFGF) can promote the proliferation of skeletal muscle satellite cells (MSCs). METHODS: MSCs were obtained from rabbits and cultured, and divided into 2 groups: rhaFGF group, treated with rhaFGF of the concentrations of 0, 5, 10, 20, 40, 60, and 80 microg/L, and rhaFGF + low molecular weight heparin (LMWH) group, treated with rhaFGF of different concentrations and LMWH of the terminal concentration of 10 mg/L. MTT method was used to observe the proliferation of the MSCs so as to determine the appropriate concentration to be used in the next experiment. Other MSCs were cultured and treated with the rhaFGF of the appropriate concentration and then LMWH of the terminal concentration of 10 mg/L was added to be co-cultured for 3 days. Flow cytometry was used to observe the cell cycle of the MSCs. RESULTS: rhaFGF of the concentrations 20 approximately 60 ng/ml promoted the proliferation of MSCs, and 40 ng/ml was selected as the best concentration to be used in the next experiment. Treated with the rhaFGF of the concentration of 40 ng/ml and LMWH for 3 days, the proportion of MSCs at the stage G(0)/G(1) was significantly lower and those at the stage S significantly higher in comparison with the control group (both P < 0.01), however, not significantly different from those of the rhaFGF group. CONCLUSION: rhaFGF promotes the proliferation of MSCs.

[The effects of 40 mg atorvastatin on serum lipids, inflammatory markers and clinical events in ACS patients post PCI].

OBJECTIVE: To assess the safety and effects of 40 mg atorvastatin on serum lipids, inflammatory markers and clinical events in ACS patients post PCI. METHODS: A total of 92 patients with ACS post successful PCI were randomly divided into atorvastatin 10 mg/d (group A) and atorvastatin 40 mg/d (group B) on top of the standard medical therapy. Blood were taken at baseline, 4, 12 and 24 weeks for serum alanine aminotransferase (ALT), lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloprotease-9 (MMP-9) measurements. The major adverse cardiac events (MACE) were also observed. RESULTS: There was no significant difference in medication withdrawn (2 vs. 3 cases) due to increased ALT (3 times higher than normal) and incidence of MACE (5 vs. 7 cases) between the groups. TC and LDL were significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 24 weeks post medication (P < 0.05) while TG and HDL remained unchanged. hs-CRP was significantly reduced at 12 and 24 weeks in both groups compared to baseline and the reduction was more significant in group B than that in group A at 24 weeks. MMP-9 was significantly reduced in both groups 4 weeks and thereafter post medication compared to pre-treatment (P < 0.05) and the reduction was more significant in group B than that in group A at 12 weeks post medication (P < 0.05). CONCLUSION: Both atorvastatin doses significantly reduced TC, LDL, hs-CRP and MMP-9 in ACS patients post PCI and the reduction was more significant in high dose atorvastatin group at 24 weeks while the MACE and drug withdraw rates were similar between the groups.