Thrombin induces a temporal biphasic vascular response through the differential phosphorylation of endothelial nitric oxide synthase via protease-activated receptor-1 and protein kinase C.

Endothelial nitric oxide synthase (eNOS) is a critical regulatory enzyme that controls vascular tone via the production of nitric oxide. Although thrombin also modulates vascular tone predominantly via the activation of protease-activated receptors (PARs), the time course and mechanisms involved in how thrombin controls eNOS enzymatic activity are unknown. eNOS enzymatic activity is enhanced by the phosphorylation of eNOS-Ser1177 and reduced by the phosphorylation of eNOS-Thr495. In this study, we hypothesized that thrombin regulates vascular tone through the differential phosphorylation of eNOS. Using rat descending aorta, we show that thrombin modulates vascular tone in an eNOS-dependent manner via activated PAR-1. We also show that thrombin causes a temporal biphasic response. Protein kinase C (PKC) is associated with second phase of thrombin-induced response. Western blot analysis demonstrated thrombin phosphorylated eNOS-Ser1177 and eNOS-Thr495 in human umbilical vein endothelial cells. A PKC inhibitor suppressed the thrombin-induced phosphorylation of eNOS-Thr495, but not that of eNOS-Ser1177. Our results suggest that thrombin induces a temporal biphasic vascular response through the differential phosphorylation of eNOS via activated PAR-1. Thrombin causes transient vasorelaxation by the phosphorylation of eNOS-Ser1177, and subsequent attenuation of vasorelaxation by the phosphorylation of eNOS-Thr495 via PKC, leading to the modulation of vascular tone.

Early detachment of prosthetic aortic valve one year after replacement for severe aortic regurgitation due to perforated aortic valve aneurysm; a case of suspected HLA-B52 positive Behçet's disease.

Herein, we report a case of 61-year-old male with congestive heart failure (HF) due to severe aortic regurgitation (AR) caused by ruptured aortic valve aneurysm (VA). Aortic valve replacement (AVR) was performed after improvement of HF symptoms. Pathological examination of resected aortic VA showed neutrophil infiltration. Although he did not have typical clinical features associated with infective endocarditis (IE) such as fever, leukocytosis, or positive blood culture, we misdiagnosed this case as "concealed IE". However, we reconsidered the etiology because prosthetic aortic valve detachment occurred only one year after AVR. When considering causes except IE for perforated aortic VA and early prosthetic valve detachment, Behçet's disease (BD) was more likely based on the clinical course, echocardiography, and pathological findings in this case. The inflammatory process of BD is associated with aortic valvulitis/aortitis, leading to a possible cause of aortic regurgitation due to aortic VA or early prosthetic valve detachment. The diagnosis of BD was challenging in this case because he did not have predominant clinical findings, including recurrent oral ulcer which is a mandatory criterion for the diagnosis by the International Study Group, however, cardiac involvement may have been the initial presentation of BD. .

Different Effects of Pulmonary Vein Isolation on Quality of Life Between Patients with Persistent and Paroxysmal Atrial Fibrillation.

The effect of restoring sinus rhythm by pulmonary vein isolation (PVI) on the quality of life (QOL) of patients with persistent atrial fibrillation (PerAF) has not been adequately investigated. This study was performed to compare the changes in QOL after extended PVI between patients with PerAF and paroxysmal AF (PAF).Patients with PAF (n = 38) and PerAF (n = 22) who underwent their first PVI and developed no AF recurrence 6 months after PVI were enrolled. QOL surveys were performed at baseline and 6 months post-ablation using Short Form-36 surveys.The mental component summary score (MCS) (53.4 ± 10.2 to 56.5 ± 7.1, P = 0.019) and physical component summary score (PCS) (46.1 ± 10.6 to 48.5 ± 8.3, P = 0.015) improved after PVI in the PAF group. The PCS, but not the MCS, improved after PVI in the PerAF group (45.8 ± 7.9 to 51.5 ± 6.2, P < 0.001). Changes in the PCS were greater in the PerAF group than in the PAF group (8.6 ± 6.9 versus 2.8 ± 5.2, P = 0.009). Multivariate regression analysis demonstrated that a low baseline MCS and the type of AF (PAF) were independent predictors of an increased MCS and that a low baseline PCS and the type of AF (PerAF) were independent predictors of an increased PCS.The changes in QOL differed between PAF and PerAF after PVI. Although most patients with PerAF were asymptomatic before PVI, their improvement in physical QOL was greater than that in patients with PAF. Such beneficial effects on physical QOL are likely expected in patients with PerAF with a low PCS before PVI.

Pre-ablation levels of brain natriuretic peptide are independently associated with the recurrence of atrial fibrillation after radiofrequency catheter ablation in patients with nonvalvular atrial fibrillation.

Association between pre-ablation levels of biomarkers of cardiac and endothelial dysfunctions, CHADS2, CHA2DS2-VASc, and APPLE scores and the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation has not been fully studied. A total of 254 patients with nonvalvular AF were prospectively followed for AF recurrence after a single ablation procedure. During a two-year follow-up period, AF recurred in 65 (25.6%) patients. Patients with AF recurrence had significantly greater baseline ln brain natriuretic peptide (BNP) than those without AF recurrence (P < 0.01), whereas there were no significant differences in the levels of biomarkers of endothelial dysfunction and points of scoring systems. In the Cox regression analyses, the baseline ln BNP was significantly independently associated with AF recurrence (adjusted HR =1.286, 95% CI =1.000-1.655, P < 0.05). The baseline levels of ln BNP were significantly associated with rhythm at blood collection, age, sex, and left atrial diameter, and left ventricular ejection fraction (P < 0.05).The subgroup analysis showed a significant interaction on the risk of AF recurrence between ln BNP, sex difference, and rhythm at blood collection (P for interaction < 0.05). In conclusion, the results suggest that the pre-ablation levels of ln BNP are useful to evaluate the risk of AF recurrence after ablation therapy; however, there is a need to be careful while using BNP as a biomarker for the risk of AF recurrence by taking account of the effects of rhythm status at blood collection and sex difference.