Curcumin promotes venous thrombi resolve process in a mouse deep venous thrombosis model via regulating miR-499.

BACKGROUND/AIMS: The morbidity of deep venous thrombosis (DVT) is increasing rapidly and the current therapeutic strategies for DVT are unsatisfactory. Accumulating evidence suggest that venous thrombi resolve (VTR) may provide new insights into DVT therapeutic strategies. The aim of this study was to investigate the role of curcumin in VTR process and try to reveal the potential mechanism. METHODS: Immunofluorescence and HE staining were performed to investigate the therapeutic angiogenesis effect of curcumin in VTR process. Microarray analysis and RT-PCR were performed to examine the expression level of miR-499 in thrombosis after curcumin administration. Cell proliferation, migration and angiogenesis capacity were tested by CCK8 assay, Transwell assay and Tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the connection between miR-499 and paired phosphate and tension homology deleted on chromosome ten (PTEN). RESULTS: We found that curcumin could effectively promote VTR process by activating angiogenesis in thrombus in vivo. The expression of miR-499 exhibited notably downregulated after curcumin administration. The proangiogenic effect of curcumin in HUVECs could be blocked by miR-499 overexpression. In addition, we confirmed that miR-499 directly target to the 3'UTR region of PTEN. CONCLUSION: Curcumin promotes VTR process in DVT through activating therapeutic angiogenesis. Mechanically, curcumin promotes therapeutic angiogenesis by regulating miR-499 mediated PTEN/VEGF/Ang-1 signaling pathway.

Apelin-APJ effects of ginsenoside-Rb1 depending on hypoxia-induced factor 1α in hypoxia neonatal cardiomyocytes.

OBJECTIVE: To investigate whether ginsenoside-Rb1 (Gs-Rb1) inhibits the apoptosis of hypoxia cardiomyocytes by up-regulating apelin-APJ system and whether the system is affected by hypoxia-induced factor 1α (Hif-1α). METHODS: Neonatal rat cardiomyocytes were randomly divided into 6 groups: a control group, a simple CoCl group, a simple Gs-Rb1 group, a CoCl and Gs-Rb1 hypoxia group, a CoCl and 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) group, a CoCl and YC-1 group and a Gs-Rb1 group, in which YC-1 inhibits the synthesis and accelerates the degradation of Hif-1a. The concentration of CoCl, Gs-Rb1 and YC-1 was 500 µmol/L, 200 µmol/L and 5 µmol/L, respectively; the apoptosis ratio was analyzed with a flow cytometer; and apelin, APJ and Hif-1α were assayed with immunocytochemistry, Western blot assays and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) The anti-apoptosis effect of Gs-Rb1 on hypoxia cardiomyocytes was significantly inhibited by YC-1; (2) Hypoxia significantly up-graded the expression of mRNA and protein of apelin; this effect was further reinforced by Gs-Rb1 and significantly inhibited by YC-1; (3) Gs-Rb1 further strengthened the expression of APJ mRNA and APJ proteins once hypoxia occurred, which was significantly inhibited by YC-1; (4) Gs-Rb1 significantly increased the expression of Hif-1α, which was completely abolished by YC-1; (5) There was a negative relationship between AR and apelin (or APJ, including mRNA and protein), a positive correlation between apelin (or APJ) protein and Hif-1a protein, in hypoxia cardiomyocytes. CONCLUSION: The apelin-APJ system plays an important role in the anti-apoptosis effect of Gs-Rb1 on hypoxia neonatal cardiomyocytes, which was partly adjusted by Hif-1α.

[Prognostic value of acute heart block after alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy].

OBJECTIVE: To investigate the prognostic value of acute heart block (AHB) after percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Ninety-four HOCM patients underwent PTSMA were included in this study. Twelve-lead electrocardiograms were obtained during and post PTSMA. Association between clinic events and incidence of post-PTSMA AHB was analyzed. RESULTS: AHB was induced in 26 patients by PTSMA and disappeared in 11 patients shortly post PTSMA, subacute intraventricular conduction disturbances was seen in 11 (42.3%), subacute I degrees AVB in 2 (7.7%) and subacute III degrees AVB in another 2 (7.7%) patients. Among 68 patients without AHB during PTSMA, intraventricular conduction disturbances was evidenced in 14 patients (20.6%), I degrees AVB in 2 (2.9%) and III degrees AVB in 1 patient (1.5%) after PTSMA. AHB patients with subacute heart block were associated with poor prognosis (conduction block duration was 42.00 h) while patients without AHB was associated with benign prognosis even with new onset of subacute heart block (conduction block duration was 7.33 h, P < 0.01). CONCLUSION: Patients with AHB during PTSMA are at higher risk for subacute heart block, especially intraventricular conduction disturbances. AHB patients with subacute heart block were associated with poor prognosis and longer recovery time of conducting system.

Complications of percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy.

OBJECTIVE: To assess the complications of percutaneous tansluminal septal myocardial ablation (PTSMA) for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Seventy-two patients with symptomatic left ventricular outflow tract obstruction were diagnosed by echocardiography or catheterization procedures. Absolute ethanol was injected into the target coronary artery branch (branches) for septal myocardial ablation. Documented complications were recorded. RESULTS: Sixty-nine patients had severe chest pain, 19 developed different degrees of heart block during the periprocedural period, but only one developed a complete AV block, requiring permanent pace-maker implantation. Temporary right bundle branch block occurred in 50% of patients and permanent block occurred in 38.9% of patients. Acute inferior myocardial infarction occurred in six patients (8.3%) and acute anterior myocardial infarction occurred in one patient. During two-year follow-up of 24 cases, there were no deaths. All patients had improvement in heart function and none experienced heart failure. CONCLUSION: The most common complication of PTSMA is right bundle branch block. The most significant complication of the procedure is heart block. PTSMA is a good technical, non-surgical treatment for HOCM.