Cardiovascular magnetic resonance image analysis and mechanism study for the changes after treatments for primary microvascular angina pectoris.

ABSTRACT: Most cases of primary microvascular angina pectoris (PMVA) are diagnosed clinically, but the etiology and pathological mechanisms are unknown. The effect of routine clinical medications is minimal, and PMVA can progress to serious cardiovascular events. To improve the diagnosis and effective treatment of this disease, this study was designed to diagnose PMVA via cardiovascular magnetic resonance (CMR) and the coronary angiography thrombolysis in myocardial infarction (TIMI) blood flow grade, as well as to analyze vascular endothelial function to elucidate the pathogenesis of PMVA and compare the effects of routine clinical medications.The present randomized controlled trial including a parallel control group will be conducted on 63 PMVA patients in our cardiovascular department. The patients will be selected and randomly divided into the control, diltiazem, and nicorandil groups. The control group will be administered routine drug treatments (aspirin, atorvastatin, betaloc ZOK, perindopril, and isosorbidemononitrate sustained-release tablets). The diltiazem group will be additionally treated with 90 mg qd diltiazem sustained-release capsules. The nicorandil group was additionally given 5 mg tid nicorandil tablets. Coronary angiography will be performed before treatment, the severity and frequency of chest pain will be evaluated before and after 9 months of treatment, and homocysteine and von Willebrand factor levels will be measured. Electrocardiography, echocardiography, dynamic electrocardiography, a treadmill exercise test, and CMR will be performed. Sex, age, body mass index, complications, smoking, and family history will also be recorded. The SPSS19.0 statistical software package will be used to analyze the data. The measurements will be expressed as the mean ±â€Šstandard deviation. Measurement data will be compared between the groups using Student's t-test. A relative number description will be used for the counting data, and the chi-squaretest will be used to compare the groups. A multivariate logistic regression analysis will be performed A P-value < .05 will be considered significant.The direct indices (CMR and coronary angiographic TIMI blood flow grade) may improve after adding diltiazem or nicorandil during routine drug treatments (such as aspirin, statins, and nitrates) in PMVA patients, and indirect indices (homocysteine and von Willebrand factor levels) may be reduced. TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org.cn/showprojen.aspx?proj=41894), No. CHiCTR1900025319, Registered on August 23, 2019; pre initiation.

A20 overexpression inhibits lipopolysaccharide-induced NF-κB activation, TRAF6 and CD40 expression in rat peritoneal mesothelial cells.

Zinc finger protein A20 is a key negative regulator of inflammation. However, whether A20 may affect inflammation during peritoneal dialysis (PD)-associated peritonitis is still unclear. This study was aimed to investigate the effect of A20 overexpression on lipopolysaccharide (LPS)-induced inflammatory response in rat peritoneal mesothelial cells (RPMCs). Isolated and cultured RPMCs in vitro. Plasmid pGEM-T easy-A20 was transfected into RPMCs by Lipofectamine™2000. The protein expression of A20, phospho-IκBα, IκBα, TNF receptor-associated factor (TRAF) 6 and CD40 were analyzed by Western blot. The mRNA expression of TRAF6, CD40, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by real time-PCR. NF-κB p65 DNA binding activity, IL-6 and TNF-α levels in cells culture supernatant were determined by ELISA. Our results revealed that RPMCs overexpression of A20 lead to significant decrease of LPS-induced IκBα phosphorylation and NF-κB DNA binding activity (all p<0.01). In addition, A20 also attenuated the expression of TRAF6, CD40, IL-6 and TNF-α as well as levels of IL-6 and TNF-α in cells culture supernatant (all p<0.05). However, A20 only partly inhibited CD40 expression. Our study indicated that A20 overexpression may depress the inflammatory response induced by LPS in cultured RPMCs through negatively regulated the relevant function of adaptors in LPS signaling pathway.

Resveratrol inhibits hydrogen peroxide-induced apoptosis in endothelial cells via the activation of PI3K/Akt by miR-126.

AIM: Resveratrol(RSV) is an edible polyphenolic phytoalexin present in different plant species that plays an important role in improving endothelial dysfunction. However, the molecular mechanisms underlying these effects are unknown. In the present study, the mechanism underlying the protection of CRL-1730 cells by RSV against oxidative stress was examined. METHODS: We first assessed the effects of RSV on the cell viability and apoptosis of CRL-1730 cells exposed to hydrogen peroxide(H2O2). Real-time PCR was used to determine the microRNA-126(miR-126) expression in cells treated with RSV and/or H2O2. We also evaluated the PI3K/Akt signaling pathway in CRL-1730 cells following upregulation of the miR-126 expression. Finally, we determined the effects of miR-126 on RSV against oxidative injury using an miR-126 inhibitor. RESULTS: Treatment with RSV resulted in a significant increase in survival and a decrease in the apoptosis of CRL-1730 cells exposed to H2O2. We also found that H2O2 significantly suppressed the expression of miR-126, which was reversed by RSV in a dose-dependent manner. The overexpression of miR-126 decreased PIK3R2(p85-ß) and enhanced Akt phosphorylation, which resulted in an increase in the survival of CRL-1730 cells exposed to H2O2. More importantly, the downregulation of the miR-126 expression reversed the effects of RSV on the survival and apoptosis of CRL-1730 cells exposed to H2O2. In addition, the knockdown of Ets-1 reversed the effects of RSV on the miR-126 expression in CRL-1730 cells exposed to H2O2. CONCLUSIONS: In this study, we demonstrated that the protection of endothelial cells by RSV against oxidative injury is due to the activation of PI3K/Akt by miR-126.

Mineralocorticoid receptor, CYP11B2 mRNA expression, and atrial matrix remodelling in patients with atrial fibrillation.

OBJECTIVE: Atrial fibrillation is associated with the activation of the renin-angiotensin-aldosterone system in the atria. It is not clear whether the expression of mineralocorticoid receptor (MR) and aldosterone synthase CYPII B2 in patients with atrial fibrillation is altered. This study aimed to investigate the mRNA expression of MR and CYPIIB2 and to reveal the correlation between CYPIIB2 mRNA and matrix remodelling in patients with atrial fibrillation. METHODS: Twenty-five patients with rheumatic heart valve disease, 12 in sinus rhythm and 13 in atrial fibrillation (> or = 6 months), underwent a valve replacement operation and right and left atrial lateral wall tissue samples were obtained. The MR and CYPI IB2 expressions were analysed at the mRNA level and collagen volume fraction was determined by Van Gieson's staining. Results - Collagen volume fraction was found to be increased significantly in atrial fibrillation groups compared with sinus rhythm groups (P < 0.001). Both the mRNA of MR and CYPIIB2 were significantly increased in the fibrillation group compared with the group in sinus rhythm (P < 0.01). Collagen volume fraction significantly and positively correlated with left atrial dimension (r = 0.845, P < 0.001).There was a positive correlation between CYPI I B2 mRNA and collagen volume fraction (r = 0.757, P < 0.001). CONCLUSION: Increased expression of MR and CYPIIB2 in the atria is one of the molecular mechanisms for the development of atrial interstitial fibrosis in patients with atrial fibrillation.

[Atrial 11beta-hydroxysteroid dehydrogenase type 2 expression in rheumatic heart disease patients with or without atrial fibrillation].

OBJECTIVE: To investigate the mRNA and protein expressions of 11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) in patients with atrial fibrillation. METHODS: Right and left atrial lateral wall tissue samples were obtained during mitral/aortic valve replacement operation from 25 patients with rheumatic heart valve disease (12 in sinus rhythm and 13 in chronic atrial fibrillation). Realtime quantitative PCR and Western blot were used to determine the mRNA and protein expressions of 11betaHSD2 in atria specimens. The distribution of 11betaHSD2 in human atrial tissue was analyzed by specific immunohistochemical staining. Echocardiography examination was performed before operation. RESULTS: The left atrial diameters were significantly higher in the atrial fibrillation group as compared to sinus rhythm group (P < 0.01). Similarly, mRNA expression of 11betaHSD2 (0.86 +/- 0.14 vs 0.33 +/- 0.12 in right atria, 0.95 +/- 0.15 vs 0.37 +/- 0.10 in left atria, all P < 0.01) and protein expression of 11betaHSD2 (1.18 +/- 0.64 vs 0.71 +/- 0.21 in right atria, P < 0.01; and 1.36 +/- 0.58 vs 0.85 +/- 0.15 in left atria, P < 0.05) were also significantly upregulated in atrial fibrillation groups than those in sinus rhythm groups. The mRNA and protein expressions of 11betaHSD2 were similar between left atria and right atria both in fibrillation and sinus groups (all P > 0.05). The special immunohistochemical staining demonstrated that 11betaHSD2 was abundant in the human atrial myocardium and located mainly in the cytoplasm. CONCLUSION: These findings suggested that upregulated 11betaHSD2 might be associated to the development and persistence of atrial fibrillation.

[Expression of mineralocorticoid receptor and 11-beta-hydroxysteroid dehydrogenase type 2 in human atria during chronic atrial fibrillation: study of 25 cases].

OBJECTIVE: To investigate the mRNA and protein expression of mineralocorticoid receptor (MR) and 11-beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), which plays a crucial role in the human heart to confer specificity on MR, in patients with chronic atrial fibrillation. METHODS: Twenty-five patients of rheumatic heart valve disease, 12 with sinus rhythm, and 13 with chronic atrial fibrillation for 6 months or over, underwent transthoracic echocardiography and mitral/aortic valve replacement operation during which right atrial lateral wall tissue samples were obtained and left atrial lateral wall tissue samples were obtained from 14 of them in addition. Realtime quantitative PCR was used to determine the mRNA expression of MR and 11betaHSD2 and Western blotting was employed to detect the protein expression of MR and 11betaHSD2 in the atrial myocardium. RESULTS: The left atrial diameters increased markedly in the atrial fibrillation group as compared to the sinus rhythm group (P < 0.01). The mRNA expression of MR in the right atrium of the patients with atrial fibrillation was 5.37 +/- 1.15, significantly higher than that of the patients with sinus rhythm (2.67 +/- 1.09, P < 0.01), the mRNA expression of MR in the left atrium of the patients with atrial fibrillation was 5.19 +/- 1.14, significantly higher than that of the patients with sinus rhythm (270 +/- 0.82, P < 0.01). The mRNA expression of 11betaHSD2 in the right atrium of the patients with atrial fibrillation was 0.86 +/- 0.14, significantly higher than that of the patients with sinus rhythm (0.33 +/- 0.12, P < 0.01), and the mRNA expression of 11betaHSD2 in the left atrium of the patients with atrial fibrillation was 0.95 +/- 0.15, significantly higher than that of the patients with sinus rhythm (0.37 +/- 0.10, P < 0.01). The protein expression of MR in the right atrial tissue of the patients with atrial fibrillation was 1.65 +/- 0.72, significantly higher than that of the patients with sinus rhythm (0.86 +/- 0.33, P < 0.01); and the protein expression of MR in the left atrial tissue of the patients with atrial fibrillation was 1.72 +/- 0.62, significantly higher than that of the patients with sinus rhythm (0.97 +/- 0.37a, P < 0.05). The protein expression of 11betaHSD2 in the right atrial tissue of the patients with atrial fibrillation was 1.18 +/- 0.64, significantly higher than that of the patients with sinus rhythm (0.71 +/- 0.21, P < 0.05); and the protein expression of 11betaHSD2 in the left atrial tissue of the patients with atrial fibrillation was 1.36 +/- 0.58, significantly higher than that of the patients with sinus rhythm (0.85 +/- 0.15, P < 0.05). The mRNA expression and protein expression of MR and 11betaHSD2 were not significantly different between the left atria and right atria both in the fibrillation and sinus groups (all P > 0.05). CONCLUSION: The mRNA expression and protein expression of MR and 11betaHSD2 are upregulated in atrial fibrillation and aldosterone antagonists may be effective to arrest the development of sustained atrial fibrillation.

[Study on expression of mineralocorticoid receptor in human atria during atrial fibrillation].

OBJECTIVE: To investigate the mRNA and protein expression of mineralocorticoid receptor (MR) in patients with atrial fibrillation. METHODS: Twenty-five patients with rheumatic heart valve disease, 12 in sinus rhythm and 13 in chronic atrial fibrillation (>or= 6 months), underwent transthoracic echocardiography and right and left atrial lateral wall tissue samples were obtained from these patients during mitral/aortic valve replacement operation. Realtime quantitative PCR and Western blot were used to determine the mRNA and protein expression of MR in atria specimens. The distribution of MR in human atria was analyzed by specific immunohistochemical staining. RESULTS: The left atrial diameters increased markedly in atrial fibrillation group compared with that in sinus rhythm group (P<0.01). And the results showed that the level of mRNA and protein of MR were increased significantly in atrial fibrillation group compared with those in sinus rhythm group (P<0.01 or 0.05), whereas the expression of mRNA and protein of MR were found to be no difference between left atria and right atria both in fibrillation and sinus groups (all P>0.05). The special immunohistochemical staining demonstrated that MR was abundant in the human atrial myocardium and MRs were located mainly in the cytoplasm of atrial cells, which were more evident in atrial fibrillation group than those in sinus rhythm group. CONCLUSION: These findings suggested that MRs were upregulated in atrial fibrillation and aldosterone antagonists may be effective in treating atrial fibrillation.

[Ablation of the orifices of the pulmonary veins under direct vision by using the transballoon ultrasound ablation catheter for permanent atrial fibrillation with rheumatic valve disease].

OBJECTIVE: To evaluate the effect and possibility of surgical ablation of the pulmonary vein orifices under direct vision with transballoon ultrasound ablation catheter for patients with permanent atrial fibrillation and rheumatic valve disease. METHODS: 21 consecutive patients with rheumatic valve disease and permanent atrial fibrillation undergoing mitral valve replacement surgery were enrolled for this study from December 2002 to September 2003. All the cases were divided into 2 groups by whether or not receiving an additive pulmonary vein ablation procedure. The test group [6 male, 5 female, aged (51.55 +/- 7.83) years, atrial fibrillation duration (5.50 +/- 5.40) years, left atrial diameter (7.27 +/- 1.39) cm, LVEF (53.95 +/- 4.54)% and NYHA class II - IV] undertook a surgical isolation of the pulmonary vein orifices by using a transballoon ultrasound ablation catheter addition to routine mitral valve replacement. The control group [3 male, 7 female, aged (53.30 +/- 7.86) years, atrial fibrillation duration (4.50 +/- 3.47) years, left atrial diameter (6.74 +/- 0.62) cm, LVEF (56.91 +/- 3.78)% and NYHA class II - IV] received the valve replacement surgery alone. RESULTS: There were not any complications in both groups. With an electrical cardioversion 3 months after the surgery, 73% patients in the ultrasound ablation group were free from AF over 1 year while only 10% patients in control group (P=0.003). During an average follow-up duration of (45.92 +/- 4.61) months, 63.6% were in sinus rhythm in ultrasound ablation group while none in the control group. Left atrial volume decreased significantly at 1 year after surgery compared to that at 3 months after surgery in the test group [(97.83 +/- 32.39) cm(3) vs. (150.78 +/- 52.32) cm(3), P<0.05], and the end systolic diameter (LAESD) and end diastolic diameter (LAEDD) also decreased [(4.12 +/- 0.39) cm vs. (5.09 +/- 0.98) cm, P<0.05, respectively], while there were no apparently changes in the control group. CONCLUSIONS: Ablation of the orifices of the pulmonary veins under direct vision with transballoon ultrasound ablation catheter during mitral valve surgery seems effective to maintain sinus rhythm after electrical cardioversion and could be performed safely. The function of left atrial and cardiac output improved during long term follow-up of 46 months.