Angiotensin II Mediates Cardiomyocyte Hypertrophy in Atrial Cardiomyopathy via Epigenetic Transcriptional Regulation.

Aims: European Heart Rhythm Association established an expert consensus to define, characterize, and classify atrial cardiomyopathy into four subgroups based on their histopathological features. The predominant pathological feature of classes I and III is the hypertrophy of atrial cardiomyocytes. Here, we aim to investigate the mechanism of epigenetic transcriptional regulation of cardiomyocyte hypertrophy in atrial cardiomyopathy. Methods and Results: Compared with that of sinus rhythm control individuals, the myocardium of patients with atrial fibrillation exhibited increased levels of angiotensin II (AngII), chromatin-bound myocyte enhancer factor 2 (MEF2), acetylated histone H4 (H4ac), and H3K27ac; upregulation of hypertrophy-related genes; and decreased levels of histone deacetylase (HDAC) 4 and HDAC5 bound to the promoters of hypertrophy-related genes. Furthermore, incubation of atrial cardiomyocytes with AngII increased their cross-sectional area and improved the expression of hypertrophy-related genes. AngII also promoted the phosphorylation of HDAC4 and HDAC5 and induced their nuclear export. RNA sequencing analyses revealed that AngII significantly upregulated genes associated with cardiac hypertrophy. Chromatin immunoprecipitation showed that this correlated with increased levels of chromatin-bound MEF2, H4ac, and H3K27ac and decreased HDAC4 and HDAC5 enrichment in the promoters of hypertrophy-related genes. Moreover, these AngII-induced prohypertrophic effects could be partially reverted by treatment with the AngII receptor blocker losartan. Conclusions: AngII had a prohypertrophic effect on atrial cardiomyopathy which was epigenetic-dependent. Patients with atrial fibrillation manifest an increased susceptibility to hypertrophy and exhibit epigenetic characteristics that are permissive for the transcription of hypertrophy-related genes. AngII induces histone acetylation via the cytoplasmic-nuclear shuttling of HDACs, which constitutes a novel mechanism of atrial hypertrophy regulation and might provide a promising therapeutic strategy for atrial cardiomyopathy.

Flow reserve fraction: the optimal choice in lesion assessing and interventional guiding for patient with unstable angina pectoris and intermediate lesion wrapped with myocardial bridge: a case report.

BACKGROUND: It is difficult to choose correctly interventional strategy for coronary intermediate lesions combined with myocardial bridge. Endovascular imaging is advocated to guide treatment, but flow reserve fraction (FFR) is not recommended to guide the interventional treatment of myocardial bridge disease because of the inaccurate judgment misled by myocardial bridge. CASE PRESENTATION: In this study, we reported a case of a 56-year-old male patient with unstable angina pectoris (UAP). From his coronary angiography, we found diffuse stenosis near the midsection of the left anterior descending (LAD) branch and the presence of a severe myocardial bridge in the lesion area. We were sure that the LAD was culprit vessel and this lesion was culprit lesion. Both FFR and intravenous ultrasound (IVUS) were performed and the conclusions of them are different. Although stent implantation is not usually recommended in the myocardial bridge area. However, after careful examination, a stent was finally implanted under the precise guidance of FFR. And the patient recovered well up-to now. CONCLUSIONS: This case illustrates that FFR functional test was complimentary to intravascular imaging test for the coronary intermediate lesion, especially the lesion wrapped with myocardial bridges, both in assessing the lesion and in guiding treatment.

Angiotensin II in atrial structural remodeling: the role of Ang II/JAK/STAT3 signaling pathway.

Ang II/JAK/STAT3 signaling pathway is known to be involved in atrial remodeling associated with development and progression of atrial fibrillation. In the present study, we used in vivo animal model and human atrial specimens to further characterize the role of this pathway in the atrial structural remodeling. We observed an elevated level of Ang II in the atrial samples of AF patients. This increase in Ang II was accompanied by increased expression of collagens I and III, MMP1, MMP2 and elevated phosphorylation of STAT3. Using rat models, we demonstrated that Ang II infusion induced profound changes in the level of apoptosis, expression of collagen subtypes I and III, caspase-3, caspase-8, MMP1, MMP2 and redistribution of cytochrome C. The data further support the key role of Ang II in the development of AF and highlight the specific mechanisms and changes associated with this process.

The role of leptin in the ventricular remodeling process and its mechanism.

OBJECTIVE: This study aims to explore the role of leptin in the ventricular remodeling process and its mechanism in the diabetic rats' model. METHODS: The diabetic SD rats model induced by streptozotocin was established. The SD rats were randomly divided into 4 groups: control group (20 rats treated with citric acid/sodium citrate buffer); M0 group (10 rats treated with physiological saline); M1 group (10 rats treated with 50 µg/kg LP); M2 group (10 rats treated with 100 µg/kg LP). Ang-II was detected by ELISA. The expression levels of LP and Ob-Rb were detected by RT-PCR. MAPK phosphorylation changes were detected by western blotting. Myocardial morphology was observed. RESULTS: Compared with control group, the blood glucose concentration and Ang-II significantly increased in diabetic model groups (P < 0.01) and body weight decreased (P < 0.05). The expression levels of LP and Ob-Rb increased and heart function decreased in diabetic model groups. CONCLUSIONS: LP may be involved in the myocardial cell hypertrophy through the neuroendocrine system and associated with the JAK-STAT, Ras-Raf-MEK-MAPK and PI-3K signaling pathway, which provides a new concept for the pathogenesis of cardiac hypertrophy.

Effects of tirofiban on platelet activation and endothelial function in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

This pilot study examined, for the first time, the effect of intracoronary administration of tirofiban, an inhibitor of platelet aggregation, on platelet activation and endothelial dysfunction in patients with ST-segment-elevated myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A total of 119 STEMI patients were randomized into either tirofiban group (n = 72, intracoronary injection of 10 µg/kg tirofiban prior to PCI, followed by intravenous infusion at 0.15 µg/kg min) or a control group (n = 47), which did not receive tirofiban. Periprocedural administration of tirofiban was associated with significantly reduced levels of platelet activation (lower levels of CD62P and PAC-1) and endothelial dysfunction (reduced levels of endothelial microparticles, VCAM-1, and ICAM-1) 48 h after PCI. At 10 days after PCI, patients in the tirofiban group had a higher incidence of complete STR (78.7 vs. 65.0%) and higher left ventricular ejection fractions (47.8 vs. 44.2) compared to those in the control group. The clinical outcomes between two groups did not differ significantly two weeks after treatment. The results demonstrated that periprocedural administration of tirofiban is associated with significantly attenuated platelet activation and endothelial dysfunction in STEMI patients undergoing PCI. This may have contributed to the improved myocardial reperfusion and preservation of left ventricular systolic function in these patients.

Correlation between brachial-ankle pulse wave velocity, carotid artery intima-media thickness, ankle-brachial index, and the severity of coronary lesions.

Coronary angiography is the gold standard for the diagnosis of coronary artery disease. Coronary artery Gensini scoring systems measure both the extent and the degree of stenosis of coronary artery and therefore, give clinicians a more accurate, objective, and comprehensive assessment of the severity of coronary artery disease. Using Gensini scoring systems in combination with statistical analysis, we found that five variables, namely, Brachial-ankle pulse wave velocity (PWV), ankle-brachial index (ABI), carotid artery intima-media thickness (IMT), blood sugar, and high density lipoprotein cholesterol (HDL-C), were all significantly different among groups of patients with different Gensini scores. All five variables can be used for early screening and assessment of coronary artery disease as independent prognostic factors for the morbidity and mortality from cardiovascular conditions. With the progression of coronary artery disease, the levels of PWV, IMT, and blood glucose are gradually increasing whereas the levels of ABI and HDL-C are gradually decreasing. These changes can be treated as warning signs and can also be helpful in evaluating the severity of coronary artery diseases. It is highly recommended to perform these five non-invasive tests as early as possible in order to identify high-risk patients at their subclinical stages. This would allow timely intervention and thereby lead to reduced morbidity and mortality from cardiovascular diseases.

Ventricular pacing on the prognosis of patients with pacemaker implantation.

Excessive right ventricular apex pacing has significant adverse effects on the cardiac function and hence, it is necessary to clinically optimize pacing parameters and advocate suitable physiological pacing to safeguard the cardiac function after pacemaker implant. Minimizing ventricular pacing is an atrioventricular node priority function, to encourage ventricular self conduction and to reduce unnecessary right ventricular pacing. Minimized ventricular pacing reduces ventricular pacing by encouraging self atrioventricular conduction function and extending the AV interval. This study is a prospective cohort study to evaluate the changes of cardiac function in patients and serum amino-terminal natriuretic peptide (NT-proBNP) before and after pacing, and the risk of atrial fibrillation with different CUM% VP. The study has shown that the cardiac function will deteriorate with an increase in pacing rate.

Non-steroidal anti-inflammatory drugs and hypertension.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to alleviate pain of the patients who suffer from inflammatory conditions like rheumatoid arthritis, osteoarthritis, and other painful conditions like gout. This class of drugs works by blocking cyclooxgenases which in turn block the prostaglandin production in the body. Most often, NSAIDs and antihypertensive drugs are used at the same time, and their use increases with increasing age. Moreover, hypertension and arthritis are common in the elderly patients requiring pharmacological managements. An ample amount of studies put forth evidence that NSAIDs reduce the efficiency of antihypertensive drugs plus aggravate pre-existing hypertension or make the individuals prone to develop high blood pressure through renal dysfunction. This review will help doctors to consider the effects and risk factors of concomitant prescription of NSAIDs and hypertensive drugs.