Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population; yet, the precise mechanisms resulting in AF are not fully understood. Caveolin-1 (Cav-1), the principal structural component of caveolae organelles in cardiac fibroblasts, is involved in several cardiovascular conditions; however, the study on its function in atrium, in particular, in AF, is still lacking. This report examines the hypothesis that Cav-1 confers an anti-AF effect by mediating atrial structural remodeling through its anti-fibrotic action. We evaluated the expression of Cav-1, transforming growth factor-β1 (TGF-β1), and fibrosis in atrial specimens of 13 patients with AF and 10 subjects with sinus rhythm, and found that the expression of Cav-1 was significantly downregulated, whereas TGF-β1 level, collagens I/III contents and atrial fibrosis were markedly increased, in AF. Western blot analysis demonstrated that treatment of human atrial fibroblasts (HAFs) with TGF-β1 resulted in a concentration- and time-dependent repression of Cav-1. Downregulation of Cav-1 with siRNA increased the TGF-β1-induced activation of Smad signal pathway and collagens production in HAFs. Furthermore, incubation of HAFs with the peptides derived from Cav-1 to achieve Cav-1 gain-of-function abolished the TGF-β1-induced production of collagens I/III and decreases of MMP-2/-9 expression. Therefore it was concluded that Cav-1 is an important anti-AF signaling mediator by conferring its anti-fibrotic effects in atrium.

Sirtuin3 (Sirt3) is a histone deacetylase involved in the regulation of many cellular processes. Sirt3 deficiency is known to increase oxidative stress. Reactive oxygen species (ROS) promote degradation of the extracellular matrix and vascular smooth muscle cell (VSMC) apoptosis. Reducing oxidative stress by Sirt3 overexpression could have therapeutic potential for limiting thoracic aortic dissection (TAD) development. We hypothesized that Sirt3 deficiency could increase the risk for TAD by decreasing ROS elimination and that Sirt3 overexpression (Sirt3OE) could provide an alternative option for TAD treatment. Mice with TAD had significantly lower Sirt3 expression than normal subjects. Sirt3 KO mice exhibit significantly increased TAD incidence rate and increased aortic diameters. Moreover, Sirt3 overexpression reduced Ang II-induced ROS production, NF-kB activation, and apoptosis in human aortic smooth muscle cells (HASMCs). Sirt3 overexpression attenuated aneurysm formation and decreased aortic expansion. In conclusion, our data showed that Sirt3 deficiency increases susceptibility to TAD formation by attenuating anti-ROS effects and increasing VSMC apoptosis and vascular inflammation.

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OBJECTIVES There is an urgent need to understand the difference in the influence of thoracoscopic surgical ablation (TSA) and catheter ablation (CA) on clinical outcomes in patients with atrial fibrillation (AF). This meta-analysis of randomized controlled trials aimed to examine the efficacy and safety of TSA versus CA in patients with AF. METHODS Databases including EMBASE, Clinical Trials, PubMed and Cochrane Central Registered Control System were screened for the retrieval of articles. A direct meta-analysis of TSA versus CA was conducted. The I2 test analysis was performed to evaluate heterogeneity. The Begg–Mazumdar test and the Harbord–Egger test were used to detect publication bias. The primary efficacy outcome was freedom from atrial tachyarrhythmia, while the primary safety outcome was severe adverse event (SAE) occurrence. RESULTS Of the 860 identified articles, 6, comprising 466 participants, were finally included. The rate of freedom from AT was higher in the TSA group (75%) than in the CA group (57.1%) (odds ratio 0.41; 95% confidence interval 0.2–0.85; P = 0.02; I2 = 57%). A larger number of SAEs were observed in the TSA group than in the CA group (odds ratio 0.16; 95% confidence interval 0.006–0.46; P = 0.0006; I2 = 44%). The result of the subgroup analysis of 3 studies that enrolled AF patients without a history of ablation showed that the incidence of AT was comparable in both arms. The ablation procedure and hospitalization durations were longer in the TSA arm. CONCLUSIONS In our study, TSA was associated with better efficacy but a higher rate of SAEs compared to CA. In addition, TSA did not show better efficacy results as the first invasive procedure in the sub-analysis of patients with paroxysmal AF or early persistent AF. Therefore, doctors should recommend either TSA or CA to patients with AF after due consideration of the aforementioned findings.

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PVI addition after successful AP or slow pathway of atrioventricular node ablation significantly reduced AF recurrence in PSVT patients with high atrial vulnerability (dERP >74.5 ms).

Serum MIF levels are a potential biomarker for reflecting the presence and severity of angiographically complex coronary lesion in CAD patients.

Group I metabotropic glutamate receptors, mGluR1 and mGluR5, are associated with sympathetic nerve activity. Sympathetic nerve stimulation exerts a crucial effect on modulating phosphorylation status and distribution of connexin43 (Cx43) in rat heart. Hence, mGluR1 and mGluR5 have an indirect effect on regulating the function of gap junction channels, which is affected by the availability of Cx43 protein. Additionally, it has been demonstrated that mGluR1/5 are present in ventricular myocardium in particular intercalated disks where Cx43 is the principal component of ventricular gap junction channels. We, therefore, hypothesized that mGluR1/5 might regulate Cx43 phosphorylation and gap junctional intercellular communication (GJIC) directly, independent of sympathetic nerve stimulation. After documenting the presence of mGluR1 and mGluR5 in H9c2 cardiomyoblast cells, addition of the selective mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) induced Cx43 phosphorylation and GJIC inhibition in both concentration- and time-dependent manner. The effects of DHPG were abolished by the mGluR1 antagonist LY367385 and the specific inhibitor of MEK1, PD98059 which also reduced phosphorylation of extracellular-signal-regulated protein kinase 1/2 (ERK1/2); but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride or the selective inhibitor of protein kinase C (PKC). In conclusion, in H9c2 cardiomyoblast cells mGluR1 increases Cx43 phosphorylation level and suppresses GJIC involving ERK1/2 but not PKC.