Valproic acid (VA) is currently used to treat epilepsy and bipolar disorder. It has also been demonstrated to promote neuroprotection and neurogenesis. Although beneficial actions of VA on brain blood vessels have also been demonstrated, the effects of VA on brain endothelial cell (EC) Ca signaling are hitherto unreported. In this report, we examined the effects of VA on agonist-triggered Ca signaling in mouse cortical bEND.3 EC. While VA (100 μm) did not cause an acute inhibition of ATP-triggered Ca signaling, a 30-min VA treatment strongly suppressed ATP-triggered intracellular Ca release; however, such treatment did not affect Ca release triggered by cyclopiazonic acid, an inhibitor of SERCA Ca pump, suggesting there was no reduction in Ca store size. VA-activated p38 signaling, and VA-induced inhibition of ATP-triggered Ca release was prevented by SB203580, a p38 inhibitor, suggesting VA caused the inhibition by activating p38. Remarkably, VA treatment did not affect acetylcholine-triggered Ca release, suggesting VA may not inhibit inositol 1,4,5-trisphosphate-induced Ca release per se, and may not act directly on Gq or phospholipase C. Taken together, our results suggest VA treatment, via a p38-dependent mechanism, led to an inhibition of purinergic receptor-effector coupling.
Nitinol (TiNi) thin film is a potentially useful material for various clinical applications, e.g., vascular stents. In this study we examined the biological functions of bovine endothelial cell (BAEC) and bovine smooth muscle cells (BSMC) on 1-mum thick amorphous TiNi films. BAEC and BSMC both attached on TiNi film, and exhibited increased cell spreading in the presence of serum containing media. Both cell types had decreased cell proliferation on TiNi as compared to glass control; however, BAEC had significantly greater proliferation rate than BSMC on TiNi. In an in vitro wound model, BSMC migrated faster than BAEC, resulting in a quicker closure of the monolayer. These results provide important insights into the interactions of vascular cells and TiNi thin film, and will help us to optimize the surface properties of TiNi film for applications in the vascular system.
Ca2+-sensing receptors (CaSR), activated by elevated concentrations of extracellular Ca2+, have been known to regulate functions of thyroid cells, neurons, and endothelial cells (EC). In this report, we studied CaSR-mediated Ca2+ influx in mouse cerebral microvascular EC (bEND.3 cells). Cytosolic free Ca2+ concentration and Mn2+ influx were measured by fura-2 microfluorometry. High (3 mM) Ca2+ (CaSR agonist), 3 mM spermine (CaSR agonist), and 10 μM cinacalcet (positive allosteric modulator of CaSR) all triggered Ca2+ influx; however, spermine, unlike high Ca2+ and cinacalcet, did not promote Mn2+ influx and its response was poorly sensitive to SKF 96365, a TRP channel blocker. Consistently, 2-aminoethoxydiphenyl borate and ruthenium red (two other general TRP channel blockers) suppressed Ca2+ influx triggered by cinacalcet and high Ca2+ but not by spermine. Ca2+ influx triggered by high Ca2+, spermine, and cinacalcet was similarly suppressed by A784168, a potent and selective TRPV1 antagonist. Our results suggest that CaSR activation triggered Ca2+ influx via TRPV1 channels; intriguingly, pharmacological, and permeability properties of such Ca2+ influx depended on the stimulating ligands.
Early post-acute myocardial infarction (AMI) pericarditis, pericardial effusion with or without cardiac tamponade, and late post-MI pericarditis (Dressler syndrome), are the major pericardial complications after AMI. It is quite rare and estimated to be only about 0.1% in AMI patients according to a recent report, so it is easily neglected or misdiagnosed and may have tragic result to patient. Clinical features of this post-AMI complication include fever, chest pain, pericarditis and pleurisy occurring 2 to 3 weeks after AMI. Dressler syndrome is rarely associated with left ventricular aneurysm. Contrast enhanced magnetic resonance and echocardiography play important roles in diagnosis of left ventricle aneurysm. We report a 54-year-old male heavy labor worker who had asymptomatic, severe coronary artery disease, complicated with silent myocardial infarction, which resulted in large left ventricular aneurysm, and also systolic heart failure was noted. Patient was diagnosed to have Dressler syndrome after his second cardiology clinic follow-up. He received coronary angiography which revealed triple vessel disease with total occlusion of left anterior descending artery, and a giant left ventricular aneurysm was found. He received surgical intervention with Batista method and followed-up uneventfully at the cardiology clinic.
Ca2+-sensing receptors (CaSRs) are G protein-coupled receptors activated by elevated concentrations of extracellular Ca2+. In our previous works, we showed protein and functional expression of CaSR in mouse cerebral endothelial cell (EC) (bEND.3); the CaSR response (high Ca2+-elicited cytosolic [Ca2+] elevation) was unaffected by suppression of phospholipase C but in part involved Ca2+ influx through transient receptor potential V1 (TRPV1) channels. In this work, we investigated if extracellular acidity affected CaSR-mediated Ca2+ influx triggered by high (3 mM) Ca2+ (CaSR agonist), 3 mM spermine (CaSR agonist), and 10 mM cinacalcet (positive allosteric modulator of CaSR). Extracellular acidosis (pH 6.8 and pH 6.0) strongly suppressed cytosolic [Ca2+] elevation triggered by high Ca2+, spermine, and cinacalcet; acidosis also inhibited Mn2+ influx stimulated by high Ca2+ and cinacalcet. Purinoceptor-triggered Ca2+ response, however, was not suppressed by acidosis. Extracellular acidity also did not affect membrane potential, suggesting suppressed CaSR-mediated Ca2+ influx in acidity did not result from the reduced electrical driving force for Ca2+. Our results suggest Ca2+ influx through a putative CaSR-TRP complex in bEND.3 EC was sensitive to extracellular pH.
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