Relationships between Community Festival Participation, Social Capital, and Subjective Well-Being in a Cross-Cultural Context.

This study explores the relationships among social capital, community festival participation, and subjective well-being (SWB). It examines the mediating role of festival participation between social capital and SWB. The dataset Social Well-being Survey in Asia from the Philippines and Thailand was collected using nationwide surveys in 2016. The total number of respondents was 1057 in the Philippines and 982 in Thailand. The results affirm several determinants related to SWB, which is composed of happiness and overall life satisfaction. The models show significant relationships among festival participation, social capital, and SWB. The results indicate strong associations among social capital with family and relatives, festival participation, and SWB. The interaction effects between the two countries are included. Structural and cognitive social capital with kinship groups were important determinants in facilitating festival participation, and positively associated with SWB. Moreover, the results identify the mediating effect of festival participation between social capital with family and relatives and SWB. The results can provide similarities and differences in the relationships among social capital and kinship groups, community festival participation, and SWB between the Philippines and Thailand. This study offers important empirical evidence of a cross-cultural study in the context of the Philippines and Thailand.

Delayed contrast enhancement imaging of a murine model for ischemia reperfusion with carbon nanotube micro-CT.

We aim to demonstrate the application of free-breathing prospectively gated carbon nanotube (CNT) micro-CT by evaluating a myocardial infarction model with a delayed contrast enhancement technique. Evaluation of murine cardiac models using micro-CT imaging has historically been limited by extreme imaging requirements. Newly-developed CNT-based x-ray sources offer precise temporal resolution, allowing elimination of physiological motion through prospective gating. Using free-breathing, cardiac-gated CNT micro-CT, a myocardial infarction model can be studied non-invasively and with high resolution. Myocardial infarction was induced in eight male C57BL/6 mice aged 8-12 weeks. The ischemia reperfusion model was achieved by surgically occluding the LAD artery for 30 minutes followed by 24 hours of reperfusion. Tail vein catheters were placed for contrast administration. Iohexol 300 mgI/mL was administered followed by images obtained in diastole. Iodinated lipid blood pool contrast agent was then administered, followed with images at systole and diastole. Respiratory and cardiac signals were monitored externally and used to gate the scans of free-breathing subjects. Seven control animals were scanned using the same imaging protocol. After imaging, the heart was harvested, cut into 1mm slices and stained with TTC. Post-processing analysis was performed using ITK-Snap and MATLAB. All animals demonstrated obvious delayed contrast enhancement in the left ventricular wall following the Iohexol injection. The blood pool contrast agent revealed significant changes in cardiac function quantified by 3-D volume ejection fractions. All subjects demonstrated areas of myocardial infarct in the LAD distribution on both TTC staining and micro-CT imaging. The CNT micro-CT system aids straightforward, free-breathing, prospectively-gated 3-D murine cardiac imaging. Delayed contrast enhancement allows identification of infarcted myocardium after a myocardial ischemic event. We demonstrate the ability to consistently identify areas of myocardial infarct in mice and provide functional cardiac information using a delayed contrast enhancement technique.

The ubiquitin ligase MuRF1 protects against cardiac ischemia/reperfusion injury by its proteasome-dependent degradation of phospho-c-Jun.

Despite improvements in interventions of acute coronary syndromes, primary reperfusion therapies restoring blood flow to ischemic myocardium leads to the activation of signaling cascades that induce cardiomyocyte cell death. These signaling cascades, including the mitogen-activated protein kinase signaling pathways, activate cardiomyocyte death in response to both ischemia and reperfusion. We have previously identified muscle ring finger-1 (MuRF1) as a cardiac-specific protein that regulates cardiomyocyte mass through its ubiquitin ligase activity, acting to degrade sarcomeric proteins and inhibit transcription factors involved in cardiac hypertrophy signaling. To determine MuRF1's role in cardiac ischemia/reperfusion (I/R) injury, cardiomyocytes in culture and intact hearts were challenged with I/R injury in the presence and absence of MuRF1. We found that MuRF1 is cardioprotective, in part, by its ability to prevent cell death by inhibiting Jun N-terminal kinase (JNK) signaling. MuRF1 specifically targets JNK's proximal downstream target, activated phospho-c-Jun, for degradation by the proteasome, effectively inhibiting downstream signaling and the induction of cell death. MuRF1's inhibitory affects on JNK signaling through its ubiquitin proteasome-dependent degradation of activated c-Jun is the first description of a cardiac ubiquitin ligase inhibiting mitogen-activated protein kinase signaling. MuRF1's cardioprotection in I/R injury is attenuated in the presence of pharmacologic JNK inhibition in vivo, suggesting a prominent role of MuRF1's regulation of c-Jun in the intact heart.

Sent to destroy: the ubiquitin proteasome system regulates cell signaling and protein quality control in cardiovascular development and disease.

The ubiquitin proteasome system (UPS) plays a crucial role in biological processes integral to the development of the cardiovascular system and cardiovascular diseases. The UPS prototypically recognizes specific protein substrates and places polyubiquitin chains on them for subsequent destruction by the proteasome. This system is in place to degrade not only misfolded and damaged proteins, but is essential also in regulating a host of cell signaling pathways involved in proliferation, adaptation to stress, regulation of cell size, and cell death. During the development of the cardiovascular system, the UPS regulates cell signaling by modifying transcription factors, receptors, and structural proteins. Later, in the event of cardiovascular diseases as diverse as atherosclerosis, cardiac hypertrophy, and ischemia/reperfusion injury, ubiquitin ligases and the proteasome are implicated in protecting and exacerbating clinical outcomes. However, when misfolded and damaged proteins are ubiquitinated by the UPS, their destruction by the proteasome is not always possible because of their aggregated confirmations. Recent studies have discovered how these ubiquitinated misfolded proteins can be destroyed by alternative "specific" mechanisms. The cytosolic receptors p62, NBR, and histone deacetylase 6 recognize aggregated ubiquitinated proteins and target them for autophagy in the process of "selective autophagy." Even the ubiquitination of multiple proteins within whole organelles that drive the more general macro-autophagy may be due, in part, to similar ubiquitin-driven mechanisms. In summary, the crosstalk between the UPS and autophagy highlight the pivotal and diverse roles the UPS plays in maintaining protein quality control and regulating cardiovascular development and disease.

Identification of binding partners for the cytoplasmic loop of connexin43: a novel interaction with ß-tubulin.

Connexin43 (Cx43), a component of gap junctions, has a relatively large carboxy-terminal region with multiple proteomic interactions. Proteomic interactions with its cytoplasmic loop, however, are poorly defined. The goal of this study is to examine proteomic interactions involving the cytoplasmic loop (CL) of Cx43. The authors utilized various techniques, including glutathione-S-transferase (GST) pull-down, immunoblot analysis, two-dimensional (2D) gel electrophoresis, and mass spectrometry, to elucidate binding partners for Cx43-CL. The authors identified novel interactions with Cx43-CL involving α- and ß-tubulin, myelin basic protein, and Purα. Because tubulin interacts with the C-terminus of Cx43 (Cx43-CT), the authors further investigated the nature of the interaction between ß-tubulin and Cx43-CL. ß-Tubulin binds with the full length of Cx43-CL with approximately one-fifth the affinity of the interaction between Cx43-CT and ß-tubulin. This study demonstrates novel proteomic interactions involving Cx43-CL that may lead to a more complete understanding of trafficking and gating of gap junction channels.

Decreased connexin43 expression in the mouse heart potentiates pacing-induced remodeling of repolarizing currents.

Gap junction redistribution and reduced expression, a phenomenon termed gap junction remodeling (GJR), is often seen in diseased hearts and may predispose toward arrhythmias. We have recently shown that short-term pacing in the mouse is associated with changes in connexin43 (Cx43) expression and localization but not with increased inducibility into sustained arrhythmias. We hypothesized that short-term pacing, if imposed on murine hearts with decreased Cx43 abundance, could serve as a model for evaluating the electrophysiological effects of GJR. We paced wild-type (normal Cx43 abundance) and heterozygous Cx43 knockout (Cx43+/-; 66% mean reduction in Cx43) mice for 6 h at 10-15% above their average sinus rate. We investigated the electrophysiological effects of pacing on the whole animal using programmed electrical stimulation and in isolated ventricular myocytes with patch-clamp studies. Cx43+/- myocytes had significantly shorter action potential durations (APD) and increased steady-state (Iss) and inward rectifier (I(K1)) potassium currents compared with those of wild-type littermate cells. In Cx43+/- hearts, pacing resulted in a significant prolongation of ventricular effective refractory period and APD and significant diminution of Iss compared with unpaced Cx43+/- hearts. However, these changes were not seen in paced wild-type mice. These data suggest that Cx43 abundance plays a critical role in regulating currents involved in myocardial repolarization and their response to pacing. Our study may aid in understanding how dyssynchronous activation of diseased, Cx43-deficient myocardial tissue can lead to electrophysiological changes, which may contribute to the worsened prognosis often associated with pacing in the failing heart.

Short-term pacing in the mouse alters cardiac expression of connexin43.

BACKGROUND: Cardiac insults such as ischemia, infarction, hypertrophy and dilatation are often accompanied by altered abundance and/or localization of the connexin43 gap junction protein, which may predispose towards arrhythmic complications. Models of chronic dyssynchronous cardiac activation have also been shown to result in redistribution of connexin43 in cardiomyocytes. We hypothesized that alterations in connexin43 expression and localization in the mouse heart might be induced by ventricular pacing over a short period of time. RESULTS: The subdiaphragmatic approach was used to pace a series of wild type mice for six hours before the hearts were removed for analysis. Mice were paced at 10-15% above their average anesthetized sinus rate and monitored to ensure 1:1 capture. Short-term pacing resulted in a significant reduction in connexin43 mRNA abundance, a partial redistribution of connexin43 from the sarcolemma to a non-sarcolemmal fraction, and accumulation of ubiquitinated connexin43 without a significant change in overall connexin43 protein levels. These early pacing-induced changes in connexin43 expression were not accompanied by decreased cardiac function, prolonged refractoriness or increased inducibility into sustained arrhythmias. CONCLUSION: Our data suggest that short-term pacing is associated with incipient changes in the expression of the connexin43 gap junction, possibly including decreased production and a slowed rate of degradation. This murine model may facilitate the study of early molecular changes induced by pacing and may ultimately assist in the development of strategies to prevent gap junction remodeling and the associated arrhythmic complications of cardiac disease.

Metabolic syndrome does not impact survival in patients treated for coronary artery disease.

OBJECTIVES: We evaluated the effect of metabolic syndrome (a risk factor for the development of coronary artery disease) on survival in patients with established coronary artery disease. METHODS: Survival was determined for 2886 patients with coronary artery disease diagnosed by cardiac catheterization performed between 1990 and 2005 at a Department of Veterans Affairs hospital. Variables obtained from the computerized medical record were evaluated in multivariate analysis by Cox regression. The analysis was performed for the entire population; separate analyses were performed for patient cohorts treated with percutaneous coronary intervention and medication (n=1274), coronary artery bypass grafting and medication (n=1096), or medication alone (n=516). RESULTS: Although age (odds ratio 0.948; P<0.000), left ventricular function (odds ratio 0.701; P<0.000), serum creatinine (odds ratio 0.841; P<0.000), and smoking (odds ratio 0.873; P=0.019) were all strong predictors of mortality. Metabolic syndrome had no independent effect irrespective of diabetic status. CONCLUSION: Metabolic syndrome does not impact survival patients with coronary artery disease treated by revascularization and/or medical therapy.