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Left atrial strain (LAS) measured by two-dimensional speckle tracking echocardiography (2DSTE) is considered to be a marker of LA structural remodeling, but it remains unsettled. We investigated the potential usefulness and clinical relevance of LAS to detect atrial remodeling including fibrosis by analyzing gene expression in cardiovascular surgery patients. Preoperative 2DSTE was performed in 131 patients (92 patients with sinus rhythm [SR] patients including paroxysmal AF [PAF], 39 atrial fibrillation [AF]) undergoing cardiovascular surgery. Atrial samples were obtained from the left atrial appendages, and mRNA expression level was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) in 59 cases (24 PAF, 35 AF). Mean value of left atrial reservoir strain (mLASr) correlated with left atrial volume index (LAVI), and left atrial conduit strain (mLAScd). mLASr also correlated with left atrial contractile strain (mLASct) in SR patients including PAF. mLASr was significantly lower, and LAVI was higher, in the AF group, compared with SR patients including PAF. The expression of COL1A1 mRNA encoding collagen type I α1 significantly increased in AF patients (p = 0.031). mLASr negatively correlated with COL1A1 expression level, and multivariate regression analysis showed that mLASr was an independent predictor of atrial COL1A1 expression level, even after adjusting for age, sex, and BMI. But, neither mLAScd / mLASct nor LAVI (bp) correlated with COL1A1 gene expression. The expression level of COL1A1 mRNA strongly correlated with ECM-related genes (COL3A1, FN1). It also correlated ECM degradation-related genes (MMP2, TIMP1, and TIMP2), pro-fibrogenic cytokines (TGFB1 encoding TGFβ1, END1, PDGFD, CTGF), oxidant stress-related genes (NOX2, NOX4), ACE, inflammation-related genes (NLRP, IL1B, MCP-1), and apoptosis (BAX). Among the fibrosis-related genes examined, univariable regression analysis showed that log (COL1A1) was associated with log (TGFB1) (adjusted R2 = 0.685, p<0.001), log (NOX4) (adjusted R2 = 0.622, p<0.001), log (NOX2) (adjusted R2 = 0.611, p<0.001), suggesting that TGFB1 and NOX4 was the potent independent determinants of COL1A1 expression level. mLASr negatively correlated with the ECM-related genes, and fibrosis-related gene expression level including TGFB1, NOX2, and NLRP3 in PAF patients. PAF patients with low mLASr had higher expression of the fibrosis-related gene expression, compared with those with high mLASr. These results suggest that LASr correlates with atrial COL1A1 gene expression associated with fibrosis-related gene expression. Patients with low LASr exhibit increased atrial fibrosis-related gene expression, even those with PAF, highlighting the utility of LAS as a marker for LA fibrosis in cardiovascular surgery patients. [ABSTRACT FROM AUTHOR]

Low-intensity endurance exercise with blood flow restriction (KAATSU) is under consideration for use in cardiac rehabilitation. However, the physiological responses to such exercise have not yet been fully characterized. In an initial effort in healthy males (n = 11, age: 26.3±4.6 y), we compared the physiological responses to low-intensity endurance exercise with and without a thigh KAATSU. Participants performed maximal graded exercise testing using a cycle ergometer with or without KAATSU. We examined responses to cycling exercise at ventilatory threshold (VT) in heart rate (HR), oxygen consumption (VO2), dyspnea, ratings of perceived exertion (RPE), blood pressure (BP), and rectus femoris activation. Participants reached VT at a lower mechanical load, HR, VO2, dyspnea, and double product (HR×systolic BP) with KAATSU vs. no-KAATSU. At VT, RPE, and rectus femoris activity did not differ between the two conditions. These results suggest that KAATSU reduced exercise intensity to reach VT and the physiological responses to exercise at VT without changes in knee extensor muscle activation. Results from this pilot study in healthy males suggest that KAATSU aerobic exercise at VT intensity has the potential to be an effective and low-burden adjuvant to cycling in cardiac rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Although pulmonary vein isolation (PVI) is an established procedure for atrial fibrillation (AF), non-PV foci play a crucial role in AF recurrence. Persistent left superior vena cava (PLSVC) has been reported as critical non-PV foci. However, the effectiveness of provocation of AF triggers from PLSVC remains unclear. This study was designed to validate the usefulness of provoking AF triggers from PLSVC. Methods: This multicenter retrospective study included 37 patients with AF and PLSVC. To provoke triggers, AF was cardioverted, and re-initiation of AF was monitored under high-dose isoproterenol infusion. The patients were divided into two groups: those whose PLSVC had arrhythmogenic triggers initiating AF (Group A) and those whose PLSVC did not have triggers (Group B). Group A underwent isolation of PLSVC after PVI. Group B received PVI only. Results: Group A had 14 patients, whereas Group B had 23 patients. After a 3-year follow-up, no difference in the success rate for maintaining sinus rhythm was observed between the two groups. Group A was significantly younger and had lower CHADS2-VASc scores than Group B. Conclusions: The provocation of arrhythmogenic triggers from PLSVC was effective for the ablation strategy. PLSVC electrical isolation would not be necessary if arrhythmogenic triggers are not provoked. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase 4 (DPP-4) is a novel adipokine and may be involved in the association between adipose tissue and metabolic syndrome. We investigated DPP-4 and adiponectin levels in the serum, subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT), and their relationship with preoperative factors, as well as comparing the DPP-4 levels in SAT and EAT with and without DPP-4 inhibitors. This study included 40 patients (25 men, age 67.5 ± 13.8 years). The serum adipokine, DPP-4, and adiponectin levels in SAT and EAT were measured using ELISA and Western blotting. The DPP-4 and adiponectin levels were significantly higher in the SAT than in the EAT. The serum DPP-4 and DPP-4 activity levels had no correlation with the DPP-4 levels in the SAT and EAT, but the DPP-4 levels in the SAT and EAT had a positive correlation. The DPP-4 levels in the SAT were positively correlated with atherosclerosis, diabetes mellitus, DPP-4-inhibitor use, and fasting blood glucose. The DPP-4 levels in the EAT showed a negative correlation with eGFR and a positive correlation with atrial fibrillation. The DPP-4 activity in the serum had a lower tendency in the group taking DPP-4 inhibitors than in the group not taking them. DPP-4 inhibitors may suppress angiogenesis and adipose-tissue hypertrophy. [ABSTRACT FROM AUTHOR]

Voltage-gated [Ca.sup.2+] channels ([Ca.sub.V]) are ubiquitously expressed in various cell types and play vital roles in regulation of cellular functions including proliferation. However, the molecular identities and function of [Ca.sub.V] remained unexplored in preadipocytes. Therefore, whole cell voltage-clamp technique, conventional/ quantitative real-time RT-PCR, Western blot, small interfering RNA (siRNA) experiments, and immunohistochemical analysis were applied in mouse primary cultured preadipocytes as well as mouse 3T3-L1 preadipocytes. The effects of [Ca.sub.V] blockers on cell proliferation and cell cycle were also investigated. Whole cell recordings of 3T3-L1 preadipocytes showed low-threshold [Ca.sub.V], which could be inhibited by mibefradil, [Ni.sup.2+] ([IC.sub.50] of 200 [micro]M), and NNC55-0396. Dominant expression of [[alpha].sub.1G] mRNA was detected among [Ca.sub.V] transcripts ([[alpha].sub.1A]-[[alpha].sub.1I]), supported by expression of [Ca.sub.V]3.1 protein encoded by [[alpha].sub.1G] gene, with immunohistochemical studies and Western blot analysis, siRNA targeted for [[alpha].sub.1G] markedly inhibited [Ca.sub.V]. Dominant expression of [[alpha].sub.1G] mRNA and expression of [Ca.sub.V]3.1 protein were also observed in mouse primary cultured preadipocytes. Expression level of [[alpha].sub.1G] mRNA and [Ca.sub.V]3.1 protein significantly decreased in differentiated adipocytes. Mibefradil, NNC55-0396, a selective T-type [Ca.sub.V] blocker, but not diltiazem, inhibited cell proliferation in response to serum. NNC55-0396 and siRNA targeted for am also prevented cell cycle entry/progression. The present study demonstrates that the [Ca.sub.V]3.1 T-type [Ca.sup.2+] channel encoded by [[alpha].sub.1G] subtype is the dominant [Ca.sub.V] in mouse preadipocytes and may play a role in regulating preadipocyte proliferation, a key step in adipose tissue development. 3T3-L1; adipose; [[alpha].sub.1G]; cell cycle doi: 10.1152/ajpcell.00488.2009.

Voltage-gated [Na.sup.+]] channel currents ([I.sub.Na]) are expressed in several types of smooth muscle cells. The purpose of this study was to evaluate the expression of [I.sub.Na], its functional role, pathophysiology in cultured human (hASMCs) and rabbit aortic smooth muscle cells (rASMCs), and its association with vascular intimal hyperplasia. In whole cell voltage clamp, [I.sub.Na] was observed at potential positive to -40 mV, was blocked by tetrodotoxin (TTX), and replacing extracellular [Na.sub.+] with N-methyl-D-glucamine in cultured hASMCs. In contrast to native aorta, cultured hASMCs strongly expressed SCN9A encoding [Na.sub.v]1.7, as determined by quantitative RT-PCR. [I.sub.Na] was abolished by the treatment with SCN9A small-interfering (si)RNA (P < 0.01). TTX and SCN9A siRNA significantly inhibited cell migration (P < 0.01, respectively) and horseradish peroxidase uptake (P < 0.01, respectively). TTX also significantly reduced the secretion of matrix metalloproteinase-2 6 and 12 h after the treatment (P < 0.01 and P < 0.05, respectively). However, neither TTX nor siRNA had any effect on cell proliferation. L-type [Ca.sup.2+] channel current was recorded, and [I.sub.Na] was not observed in freshly isolated rASMCs, whereas TTX-sensitive [I.sub.Na] was recorded in cultured rASMCs. Quantitative RT-PCR and immunostaining for [Na.sub.v]1.7 revealed the prominent expression of SCN9A in cultured rASMCs and aorta 48 h after balloon injury but not in native aorta. In conclusion, these studies show that [I.sub.Na] is expressed in cultured and diseased conditions but not in normal aorta. The [Na.sub.v]l.7 plays an important role in cell migration, endocytosis, and secretion. [Na.sub.v]1.7 is also expressed in aorta after balloon injury, suggesting a potential role for [Na.sub.v]1.7 in the progression of intimal hyperplasia. vascular smooth muscle; sodium channel; SCN9A; balloon injury

Denitrification is a well-studied respiratory system that is also important in the biogeochemical nitrogen cycle. Environmental signals such as oxygen and N-oxides have been demonstrated to regulate denitrification, though how denitrification is regulated in a bacterial community remains obscure. Pseudomonas aeruginosa is a ubiquitous bacterium that controls numerous genes through cell-to-cell signals. The bacterium possesses at least two N-acyl-L-homoserine lactone (AHL) signals. In our previous study, these quorum-sensing signals controlled denitrification in P. aeruginosa. In addition to the AHL signals, a third cell-to-cell communication signal, 2-heptyl-3-hydroxy-4-quinolone, referred to as the Pseudomonas quinolone signal (PQS), has been characterized. In this study, we examined the effect of PQS on denitrification to obtain more insight into the respiratory regulation in a bacterial community. Denitrification in P. aeruginosa was repressed by PQS, which was partially mediated by PqsR and PqsE. Measuring the denitrifying enzyme activities indicated that nitrite reductase activity was increased by PQS, whereas PQS inhibited nitric oxide reductase and the nitrate-respiratory chain activities. This is the first report to demonstrate that PQS influences enzyme activities, suggesting this effect is not specific to P. aeruginosa. Furthermore, when iron was supplied to the PQS-added medium, denitrifying activity was almost restored, indicating that the iron chelating property of PQS affected denitrification. Thus, our data indicate that PQS regulates denitrification primarily through iron chelation. The PQS effect on denitrification was relevant in a condition where oxygen was limited and denitrification was induced, suggesting its role in controlling denitrification where oxygen is present.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that is one of the most refractory to therapy when it forms biofilms in the airways of cystic fibrosis patients. To date, studies regarding the production of an immunogenic and protective antigen to inhibit biofilm formation by P. aeruginosa have been superficial. The previously uncharacterized outer membrane protein (OMP) Opr86 (PA3648) of P. aeruginosa is a member of the Omp85 family, of which homologs have been found in all gram-negative bacteria. Here we verify the availability of Opr86 as a protective antigen to inhibit biofilm formation by P. aeruginosa PAO1 and several other isolates. A mutant was constructed in which Opr86 expression could be switched on or off through a tac promoter-controlled opr86 gene. The result, consistent with previous Omp85 studies, showed that Opr86 is essential for viability and plays a role in OMP assembly. Depletion of Opr86 resulted in streptococci-like morphological changes and liberation of excess membrane vesicles. A polyclonal antibody against Opr86 which showed reactivity to PAO1 cells was obtained. The antibody inhibited biofilm formation by PAO1 and the other clinical strains tested. Closer examination of early attachment revealed that cells treated with the antibody were unable to attach to the surface. Our data suggest that Opr86 is a critical OMP and a potential candidate as a protective antigen against biofilm formation by P. aeruginosa.

Anaerobic growth of Pseudomonas aeruginosa PAO1 was affected by quorum sensing. Deletion of genes that produce N-acyl-L-homoserine lactone signals resulted in an increase in denitrification activity, which was repressed by exogenous signal molecules. The effect of the/as quorum-sensing system was dependent on the rhl quorum-sensing system in regulating denitrification.