Renalase mediates macrophage-to-fibroblast crosstalk to attenuate pressure overload-induced pathological myocardial fibrosis.

A potential antifibrotic mechanism in pathological myocardial remodeling is the recruitment of beneficial functional subpopulations of macrophages or the transformation of their phenotype. Macrophages are required to activate molecular cascades that regulate fibroblast behavior. Identifying mediators that activate the antifibrotic macrophage phenotype is tantamount to identifying the button that retards pathological remodeling of the myocardium; however, relevant studies are inadequate. Circulating renalase (RNLS) is mainly of renal origin, and cardiac myocytes also secrete it autonomously. Our previous studies revealed that RNLS delivers cell signaling to exert multiple cardiovascular protective effects, including the improvement of myocardial ischemia, and heart failure. Here, we further investigated the potential mechanism by which macrophage phenotypic transformation is targeted by RNLS to mediate stress load-induced myocardial fibrosis. Mice subjected to transverse aortic constriction (TAC) were used as a model of myocardial fibrosis. The co-incubation of macrophages and cardiac fibroblasts was used to study intercellular signaling. The results showed that RNLS co-localized with macrophages and reduced protein expression after cardiac pressure overload. TAC mice exhibited improved cardiac function and alleviated left ventricular fibrosis when exogenous RNLS was administered. Flow sorting showed that RNLS is essential for macrophage polarization towards a restorative phenotype (M2-like), thereby inhibiting myofibroblast activation, as proven by both mouse RAW264.7 and bone marrow-derived macrophage models. Mechanistically, we found that activated protein kinase B is a major pathway by which RNLS promotes M2 polarization in macrophages. RNLS may serve as a prognostic biomarker and a potential clinical candidate for the treatment of myocardial fibrosis.

Butyric Acid Ameliorates Myocardial Fibrosis by Regulating M1/M2 Polarization of Macrophages and Promoting Recovery of Mitochondrial Function.

Background: We aimed to investigate the effect and mechanism of butyric acid on rat myocardial fibrosis (MF). Methods: 16S rRNA sequencing was used to analyze the gut microbiota characteristics of the Sham group and MF group. HPLC was applied to measure butyric acid in the feces and serum. In vitro, rat macrophages RMa-bm were stimulated with LPS and IL-4, respectively, and then butyrate was added to study the influences of butyrate on M1/M2 polarization and mitochondrial function of rat macrophages. The rat macrophages and rat myocardial fibroblasts were co-cultured to explore the effect of butyrate on rat myocardial fibroblasts. In addition, MF rats were fed with butyric acid diet. Results: Compared with the Sham group, collagen deposition in the MF group was increased, and fibrosis was serious. The abundance of Desulfovibrionaceae and Helicobacteraceae in the MF group was increased compared with the Sham group. Gut epithelial cells were destroyed in the MF group compared with the Sham group. Compared with the Sham group, LPS content in the MF group was increased and butyric acid was decreased. Butyrate inhibited M1 and promoted M2. Furthermore, butyrate may promote mitochondrial function recovery by regulating M1/M2 polarization of macrophages. After adding butyrate, cell proliferation ability was decreased, and aging and apoptosis were increased, which indicated that butyrate inhibited rat myocardial fibroblasts activity. Moreover, butyric acid could protect mitochondria and improve the symptoms of rats with MF. Conclusions: Butyric acid ameliorated MF by regulating M1/M2 polarization of macrophages and promoting recovery of mitochondrial function.

The effect of heart rate on blood pressure measurement in patients with atrial fibrillation: a cross-sectional study.

This study explored the effect of heart rate (HR) on the stability and accuracy of blood pressure (BP) measurement and the optimal HR range for the most accurate blood pressure measurement in atrial fibrillation (AF) patients. A total of 583 patients (383 and 200 with AF and sinus rhythm (SR), respectively) were included in this study. The noninvasive blood pressure (NIBP), invasive blood pressure (IBP), and HR were repeatedly measured ten times at 30-second intervals for every patient. Both the AF and SR groups were then subdivided into five groups depending on the HR (i.e., < 60, 60-80, 80-100, 100-120, and ≥120 bpm). The difference between the IBP and NIBP (i.e., △SBP) and the coefficient of variation (CV) were calculated, and the stability and accuracy of NIBP measurements were analyzed. CV and △SBP were significantly higher in the AF group. In the AF group, the CV of NIBP was highest when the HR was ≥ 100 bpm; and △SBP was significantly lower in the HR groups with 60-80 and 80-100 bpm (< 60 bpm, △SBP 11.62 ± 2.64 mmHg; 60-80 bpm, △SBP 7.10 ± 1.92 mmHg; 80-100 bpm, △SBP 7.10 ± 2.95 mmHg; 100-120 bpm, △SBP 10.52 ± 2.72 mmHg; ≥120 bpm, △SBP 14.15 ± 3.61 mmHg, P < 0.05). The stability and accuracy of the NIBP in the SR groups were not affected by the HR. In AF patients, the NIBP stability was low when the HR was high, and the NIBP was often underestimated when the HR was high or low. Sixty to 100 bpm is the best HR range for measuring blood pressure in AF patients.

A new ECG sign for sudden death: Transient prolonged QT interval following premature contraction. / 一种新的猝死预警心电图：期前收缩后短暂QT间期延长.

Early recognition and treatment for early warning electrocardiogram (ECG) of sudden death are very important to prevent and treat malignant arrhythmia and sudden death. Previous studies have found that R-on-T and T wave alternation, and QT interval prolongation are closely related to malignant arrhythmia or sudden death, which are included in the critical value of ECG.By analyzing the ECG characteristics of 4 patients with sudden death, we found that although the causes of the patients were different, there were transient prolongation of QT interval after premature contraction in 12 lead ECG, followed by malignant arrhythmia or sudden death. Thus, we thought that the transient prolongation of QT interval after premature contraction had a high value for warning malignant arrhythmia or sudden death. This phenomenon should be paid enough attention to reduce the risk of sudden death.

Analysis of situation of acute coronary syndrome based on the date of the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project: single-centre observational study.

BACKGROUND: We are currently faced with an increasing burden of cardiovascular disease in China and the inadequacy of the application of guidelines in clinical practice. In the past decade, China has been strengthening the healthcare system, but it still lacked a national performance measurement system and an appropriate quality improvement strategy. Therefore, in order to improve the implementation of guideline recommendations in clinical practice, China has learnt from the successful experience of Get With The Guidelines project in 2014. Under the guidance of the Medical and Health Hospital of the National Health and Family Planning Commission, the Chinese Society of Cardiology and the American Heart Association jointly launched the Improving Care for Cardiovascular Disease in China (CCC) project. The project team provided an analysis report on the completion of key medical quality evaluation indicators of each hospital every month, supplied guidance through education, training, experience exchange and on-site investigation for problems, and certified hospitals with outstanding performance and obvious progress. The circle pattern, including evaluation, training, improvement and re-evaluation, will boost the guidelines compliance on clinical practice in China and improve the quality of medical services. METHODS: This study was conducted in a centre of the Third Xiangya Hospital of Central South University. It included patients with ACS from December 2009 to December 2011 (n=225), patients with ACS in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project coming from the Third Xiangya Hospital of Central South University (n=665), 12 hospitals in Hunan Province (n=4333) and 150 hospitals in China (n=63 641) from November 2014 to April 2017. It assessed the situation of drug therapy, hospitalisation day, mortality during hospitalisation, median of door-to-needle (D-to-N) time and median of door-to-balloon (D-to-B) time of patients with ST-segment elevation myocardial infarction (STEMI), the proportion of D-to-N within 30 min and D-to-B within 90 min, and the proportion of reperfusion therapy. Patients with ACS from the centre from November 2014 to April 2017 were divided into five groups (every 6 months as a group according to time). The study observed change trends in all the above-mentioned indexes. RESULTS: Compared with before participating in the CCC project, there were increases after participating in the CCC project in the drug usage rates of aspirin, P2Y12 inhibitor (clopidogrel or ticagrelor), ß-blocker, statin and angiotensin converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB). Hospitalisation day and mortality during hospitalisation were shortened. D-to-N and D-to-B times of patients with STEMI were shorter. Compared with Hunan Province and China, the drug usage rates were higher; hospitalisation day and D-to-N time were shorter; D-to-B time was longer; and the proportion of reperfusion therapy was higher. The trend of drug usage rates was on the rise. There was no significant change in the hospitalisation day and D-to-N and D-to-B times. The mortality during hospitalisation showed a downward trend. The proportion of D-to-N within 90 min and reperfusion therapy showed upward trends. CONCLUSION: Quality of care for patients with ACS improved over time in the CCC project, including taking medicine following the guidelines, increased use of reperfusion therapy and faster time to treatment. Although overall mortality has improved, we also should attach importance to high-risk patients. The influence of the CCC project, which is based on guidelines on prognosis of ACS in the centre, presents an important clinical implication that it is necessary to enhance adherence to the guidelines in the treatment of ACS.

Sex differences in antihypertensive drug use and blood pressure control.

BACKGROUND: Hypertension is the most important modifiable cardiovascular risk factor. Epidemiological studies have shown the benefits of lowering blood pressure (BP), but BP control is a major challenge. Furthermore, there are significant sex differences in antihypertensive drug use and BP control. This study examined sex differences in antihypertensive drug use and BP control, with the aim of reducing the complications of hypertension and improving quality of life. METHODS: The study was performed in our outpatient hypertension clinic, and included 1529 patients without secondary hypertension or comorbidities. The study, investigated BP control rates and patterns of antihypertensive drug use in male and female. All data were collected using structured questionnaires and patient measurements. RESULTS: The study included 713 males and 816 females in this study. Fewer females had hypertension in the younger age group (16.2% vs 11.6%; p>0.05), but this difference disappeared in middle-aged (47.8% vs 49.9 %; p<0.05) and elderly age groups (36.0% vs 38.5%; p<0.05). BP control rates differed between males and females (35.6% in male, 31.9% in female, p<0.01). There was an overall difference in BP control rates between males and females (35.6% in males, 31.9% in females, p<0.01). In this aged 18-44 years, angiotensin converting enzyme inhibitors (ACEIs) showed the best control rate in males, while calcium channel blockers (CCBs) were least effective (61.5% with ACEIs, 28.6% with CCBs; p<0.05). In this aged 45-64 years, diuretics (DUs) showed the best control rate in females, while CCBs were least effective (47.5% with DUs, 28.3% with CCBs; p<0.05). CONCLUSIONS: Sex plays an important role in BP control. In those aged 18-44 years, males using ACEIs showed best control rates. In those aged 45-64 years, females using DUs showed best control rates. Our study provides a basis with the selection of antihypertensive drugs according to sex and age.