Omega-3 fatty acid protects cardiomyocytes against hypoxia-induced injury through targeting MiR-210-3p/CASP8AP2 axis.

MicroRNAs (miRs) regulate diverse biological functions in both normal and pathological cellular conditions by post-transcriptional regulation of various genes expression. Nevertheless, the role of miRs in regulating the protective functions of omega-3 fatty acid in relation to hypoxia in cardiomyocytes remains unknown. The aim of this study was to investigate the effects of omega-3 fatty acid supplementation on cardiomyocyte apoptosis and further delineate the mechanisms underlying microRNA-210 (miRNA-210)-induced cardiomyocyte apoptosis in vitro. H9C2 cultured cells were first subjected to hypoxia followed by a subsequent treatment with main component of the Omega-3 fatty acid, Docosahexaenoic Acid (DHA). Cell apoptosis were detected by flow cytometry and the expression of miR-210-3p were detected by RT-qPCR and caspase-8-associated protein 2 (CASP8AP2) at protein levels by immunoblotting. Dual luciferase assay was used to verify the mutual effect between miR-210-3p and the 3'-untranslated region (UTR) of CASP8AP2 gene. DHA was shown to reduce apoptosis in H9C2 cells subjected to hypoxia. While DHA caused a significant increase in the expression of miR-210-3p, there was a marked reduction in the protein expression of CASP8AP2. MiR-210-3p and CASP8AP2 were significantly increased in H9C2 cardiomyocyte subjected to hypoxia. Overexpression of miR-210-3p could ameliorate hypoxia-induced apoptosis in H9C2 cells. MiR-210-3p negatively regulated CASP8AP2 expression at the transcriptional level. Both miR-210-3p mimic and CASP8AP2 siRNA could efficiently inhibit apoptosis in H9C2 cardiomyocyte subjected to hypoxia. We provide strong evidence showing that Omega-3 fatty acids can attenuate apoptosis in cardiomyocyte under hypoxic conditions via the up-regulation of miR-210-3p and targeting CASP8AP2 signaling pathway.

Association of Serum Omentin-1 Concentrations with the Presence of Atrial Fibrillation.

BACKGROUND Omentin-1 is one of the adipokines associated with obesity, diabetes, and coronary heart disease development. We determined to investigate whether serum omentin-1 concentrations were correlated with the presence of atrial fibrillation (AF). MATERIAL AND METHODS Serum omentin-1 concentrations were examined in a cross-sectional population that included 220 patients with AF (70 with paroxysmal AF, 78 with persistent AF, and 72 with permanent AF) and 115 healthy controls. RESULTS Reduced serum omentin-1 concentrations were found in AF patients compared to the controls. In addition, patients with permanent AF had lower serum omentin-1 concentrations compared to patients with persistent AF and patients with paroxysmal AF. Significantly decreased serum omentin-1 concentrations were observed in persistent AF patients compared to paroxysmal AF patients. Spearman correlation analysis suggested that serum omentin-1 concentrations were negatively correlated with left atrial diameter in AF patients. CONCLUSIONS Serum omentin-1 concentrations were correlated with the presence of AF and atrial remolding.

Circulating miR-30 is related to carotid artery atherosclerosis.

OBJECTIVES: The aim of this study is to evaluate the relationship of miR-30 with office and ambulatory blood pressure parameters and carotid intima-media thickness (CIMT) in patients with hypertension and healthy controls. METHODS: We assessed the expression level of miR-30 in 40 patients with essential hypertension and 40 healthy individuals. All patients underwent carotid artery ultrasonography, and office and ambulatory blood pressure monitoring. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of selected miR-30. The miR-30 expression level correlation between blood pressure parameters and CIMT was assessed using the Spearman correlation coefficient. Multiple logistic regression analysis was performed to assess independent association between miR-30 expression level and CIMT. RESULTS: We observed lower expression level of miR-30 (26.01 ± 2.40 vs. 28.26 ± 1.28; p < 0.001) in hypertensive patients compared with healthy control individuals, as well as in increased CIMT group compared with normal CIMT group (25.09 ± 1.84 vs. 27.81 ± 2.37; p < 0.001). miR-30 expression level showed significant negative correlation with 24 h mean SBP (r = -0.51, p < 0.001), 24 h mean DBP(r = -0.316, p = 0.004), office SBP(r = -0.502, p < 0.001), office DBP (r = -0.205, p = 0.068), and CIMT (r = -0.578, p < 0.001), respectively. The odds ratio for CIMT was 0.519 (B = -0.748, CI 95% 0.278, 0.806; p = 0.006). CONCLUSION: Our study suggests that circulating miR-30 might be used as a biomarker for atherosclerosis in essential hypertensive patients.

Circulating miR155 expression level is positive with blood pressure parameters: Potential markers of target-organ damage.

OBJECTIVES: The aim of this study is to evaluate the relationship of miR155 with office and ambulatory blood pressure (BP) parameters and left ventricular hypertrophy (LVH) in patients with hypertension and healthy controls. METHODS: We assessed the expression level of the miR155 in 50 patients with essential hypertension and 30 healthy individuals. All patients underwent two-dimensional echocardiography, office BP monitoring and ambulatory blood pressure monitoring (ABPM). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression of selected miR155. The miR155 correlations between BP parameters and left ventricular mass index (LVMI) were assessed using the Spearman correlation coefficient. RESULTS: We observed higher expression level of miR155 (33.22 ± 2.59 vs. 27.30 ± 1.76; p < 0.001) in hypertensive patients compared with healthy control individuals, as well as in LVH to nLVH group (33.00 ± 2.78 vs. 27.28 ± 1.76; p < 0.001). MiR155 expression level showed significant positive correlations with office measurement of systolic blood pressure (SBP) (r = 0.634, p < 0.001), diastolic blood pressure (DBP) (r = 0.222, p < 0.05), pulse pressure (PP) (r = 0.564, p < 0.001), respectively. And explored miR155 expression level in relation to 24-h ABPM parameters showed significant positive correlation with 24 h mean SBP (r = 0.67, p < 0.001), 24 h mean DBP (r = 0.257, p < 0.05), 24 h mean PP (r = 0.597, p < 0.001), respectively, as well as with LVMI (r = 0.591, p < 0.001). CONCLUSION: Circulating miR155 may possibly represent potential non-invasive marker of hypertension and target organ damage (TOD) in essential hypertensive patients.

Objective Ischemia, Subjective Angina, and Psychological Distress in Angina With No Obstructive Coronary Disease.

BACKGROUND: Angina with no obstructive coronary disease (ANOCA) and ischemia with no obstructive coronary disease, prevalent yet underrecognized conditions, mostly affect women. Previous studies rarely distinguished between them. We aimed to compare the prevalence of objective ischemia through various examinations in women with ANOCA and assess the impact of objective and subjective ischemia on their mental health. METHODS AND RESULTS: A total of 84 eligible women with ANOCA and 42 controls underwent mental stress, pharmacological stress, exercise stress, and Holter testing. Objective evidence of myocardial ischemia was assessed by positron emission tomography-computed tomography and ECG, and subjective symptoms were graded using the Canadian Cardiovascular Society scale (CCS). Psychological assessments were conducted using 6 scales. Among 84 women with ANOCA, 37 (44%) received a diagnosis of ischemia with no obstructive coronary disease following mental stress testing, 20 (28.6%) through pharmacological stress testing, 14 (21.2%) via exercise stress testing, and 24 (32.9%) from Holter. Mental stress-induced myocardial ischemia was more prevalent (P<0.05). Among 54 patients with ANOCA who completed all tests, 30% showed no ischemia, and only 1 (1.9%) showed ischemia in all tests. In addition, patients with ANOCA had higher psychological scores than controls (P<0.01). No significant differences was observed in psychological scores between ANOCA with positive and negative ischemia test results (P>0.05). However, ANOCA with milder angina (CCS I) exhibited higher scores across the Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Perceived Stress Scale, and Posttraumatic Stress Disorder Checklist-Civilian Version and a higher prevalence of Type D personality traits (P<0.05). CONCLUSIONS: In patients with ANOCA, the positive rate of myocardial ischemia exhibits variability among several noninvasive tests. A worsened psychological state is more closely linked to milder angina symptoms than to ischemia performance, highlighting the importance of focusing on symptom management in their psychological care. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03982901.

Trends in Unhealthy Lifestyle Factors among Adults with Stroke in the United States between 1999 and 2018.

BACKGROUND: Unhealthy lifestyle factors are risk factors for stroke, and they play a key role in stroke secondary prevention. A better understanding of these factors may aid with improvements in public health policy. OBJECTIVE: Our objective was to comprehensively understand the trends in unhealthy lifestyle factors in people who have previously had a stroke in the US. METHODS: Utilizing data from the biannual United States National Health and Nutrition Examination Surveys (NHANESs) between 1999 and 2018, we collated data on unhealthy lifestyle factors (smoking, alcohol drinking, depression, unhealthy diet, high BMI, physical inactivity, and sedentary behavior) in adults with a history of stroke. The Joinpoint Regression model was used to calculate the annual percentage change (APC) and average annual percentage change (AAPC) to identify trends. Logistic regression modeling was used to identify the influence of sociodemographic factors (age, sex, race/ethnicity, marital status, employment status, family income, and highest education level). RESULTS: The analysis included 2017 respondents with a history of stroke. Current alcohol drinking (39.3% (95% confidence interval: 29.8, 48.7) to 57.4% (45.7, 69.0) p = 0.008) and obesity (39.2% (28.3, 50.2) to 49.4% (38.9, 59.8) p = 0.029) increased significantly from 1999 to 2018. The prevalence of smoking and depression remained generally stable. The proportion of respondents with an unhealthy diet decreased from 1999 (44.5% (32.4, 56.5)) to 2011 (29.0% (17.5, 40.4) p = 0.019), but then returned to its original prevalence in 2018 (42.0% (31.4, 52.7)). From 2007 to 2018, the proportion of respondents who were physically inactive decreased significantly, from 70.4% (64.4, 76.3) to 55.1% (46.1, 64.2; p = 0.017). After a gradual increase in sedentary activity from 2007 to 2012, this declined from 2013 to 2018, with no statistical significance. We found stroke survivors who were widowed, divorced, separated, or unemployed were at a higher risk of having unhealthy lifestyles than those who were employed or had other marital statuses. CONCLUSIONS: A modest reduction in the prevalence of physical inactivity was observed in Americans with a history of stroke between 1999 and 2018. The prevalences of smoking, drinking, depression, poor diet, obesity, and sedentary behavior were stable or increasing.

Trends in unhealthy lifestyle factors in US NHANES respondents with cardiovascular disease for the period between 1999 and 2018.

Objectives: To examine national trends in unhealthy lifestyle factors among adults with cardiovascular disease (CVD) in the United States (US) between 1999 and 2018. Methods: We analyzed data from National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of participants with CVD who were aged ≥20 years, which was conducted between 1999 and 2000 and 2017-2018. CVD was defined as a self-report of congestive heart failure, coronary heart disease, angina, heart attack, or stroke. The prevalence rate of each unhealthy lifestyle factor was calculated among adults with CVD for each of the 2-year cycle surveys. Regression analyses were used to assess the impact of sociodemographic characteristics (age, sex, race/ethnicity, family income, education level, marital status, and employment status). Results: The final sample included 5610 NHANES respondents with CVD. The prevalence rate of their current smoking status remained stable among respondents with CVD between 1999 and 2000 and 2017-2018. During the same period, there was a decreasing trend in the age-adjusted prevalence rate of poor diet [primary American Heart Association (AHA) score <20; 47.5% (37.9%-57.0%) to 37.5% (25.7%-49.3%), p < 0.01]. Physical inactivity marginally increased before decreasing, with no statistical significance. The prevalence rate of sedentary behavior increased from 2007 to 2014 but subsequently returned to its original level in 2018 with no statistical significance. The age-adjusted prevalence rate of obesity increased from 32% (27.2%-36.8%) in 1999-2000 to 47.9% (39.9%-55.8%) in 2017-2018 (p < 0.001). The age-adjusted prevalence rate of depression increased from 7% (4.2%-9.9%) in 1999-2000 to 13.9% (10.2%-17.6%) in 2017-2018 (p = 0.056). Trends in mean for each unhealthy lifestyle factor were similar after adjustment for age. We found that respondents who had low education and income levels were at a higher risk of being exposed to unhealthy lifestyle factors (i.e., smoking, poor diet, and physical inactivity) than those who had high education and income levels. Conclusions: There is a significant reduction in the prevalence rate of poor diet among US adults with CVD between 1999 and 2018, while the prevalence rate of obesity showed increasing trends over this period. The prevalence rate of current smoking status, sedentary behavior, and depression was either stable or showed an insignificant increase. These findings suggest that there is an urgent need for health policy interventions targeting unhealthy lifestyles among adults with CVD.

Job Burnout Is Associated With Prehospital Decision Delay: An Internet-Based Survey in China.

Background: Prehospital delay is associated with non-modifiable factors such as age, residential region, and disease severity. However, the impact of psychosocial factors especially for job burnout on prehospital decision delay is still little understood. Method: This internet-based survey was conducted between 14 February 2021 and 5 March 2021 in China through the Wechat platform and web page. Self-designed questionnaires about the expected and actual length of prehospital decision time and the Chinese version of Maslach Burnout Inventory-General Survey, Type D Personality Scale-14, and Social Support Rating Scale were applied. A total of 1,039 general participants with a history of perceptible but tolerable body discomfort were included. Results: The top six reasons for prehospital decision delay were: (1) endure until self-healing (50.7%), (2) too busy to ask for leave (40.3%), (3) process for seeing a doctor too complicated (35.8%), (4) too tired after work (26.2%), (5) worry about the expenditure (16.6%), and (6) fear of being identified as with serious problem (14.5%). The univariate analyses revealed that older age (p = 0.001), type D personality (p = 0.025), job burnout (p = 0.055), and worrying about expenditure (p = 0.004) were associated with prolonged prehospital decision time, while engaged in medical-related job (p = 0.028) and with more social support (p = 0.066) would shorten the delay. The multivariate analysis using logistic regression model with forward selecting method showed that age [per 10 years, odds ratio (OR) 1.19 (1.09-1.31), p < 0.001], job burnout [per 10 points in Maslach Burnout Inventory-General Survey (MBI-GS), OR 1.17 (1.04-1.31), p = 0.007], and worrying about expenditure [OR 1.75 (1.25-2.47), p = 0.001] were the three determinants for prehospital decision delay (>7 days). Mediating effects were analyzed by using bias-corrected percentile bootstrap methods (N = 10,000). Social support was found partially mediated the relationship between the determinants and prehospital decision time. The partial mediating effect of social support accounted for 24.0% of the total effect for job burnout and 11.6% for worrying about expenditure. Conclusion: Psychosocial factors have a non-negligible impact on prehospital decision delay. The crucial part of prehospital decision delay may be the lack of motivation inside. Job burnout and lack of social support, as two commonly seen features in the modern world, should be given enough consideration in disease prevention and treatment.

The Effect of Total Cholesterol Variability on Clinical Outcomes After Percutaneous Coronary Intervention.

AIM: Exploring the risk factors of prognosis in patients undergoing percutaneous coronary intervention (PCI) is of great importance. Our aim of the study is to investigate the association between variability in total cholesterol (TC) level and major adverse cardiovascular and cerebrovascular events (MACCE) in patients after PCI. METHODS: Between April 2004 and December 2009, 909 patients who underwent primary PCI and with at least three TC values were included in the final study. TC variability was calculated using four indices: standard deviation (SD), coefficient of variation (CV), the average successive variability (ASV), variability independent of the mean (VIM). MACCE comprised all-cause mortality, non-fatal myocardial infarction (MI), unplanned revascularization, hospitalization for heart failure, and non-fatal stroke. RESULTS: There were 394 cases of MACCE during the follow-up period. When the subjects were divided into quartile groups by CV of TC, high CV groups were associated with a higher hazard ratio of MACCE than for lower CV groups. In multivariable adjusted models, TC variability and MACCE remained correlated [HR (95% CI): Q2, 1.17 (0.86-1.58); Q3, 1.38 (1.03-1.85); Q4, 1.63 (1.22-2.17)]. Similar patterns of MACCE were noted by quartiles of SD, ASV, and VIM. CONCLUSION: Visit-to-visit TC variability is positively correlated with MACCE in patients after PCI.

The salivary-α-amylase level after stroop test in anxious patients can predict the severity of anxiety.

Individuals with anxiety disorder often exhibit as imbalance in response to stressors. We sought to explore the relationship between physiological as well as psychological responses under acute mental stress and the severity of the disease. 20 Generalized Anxiety Disorder (GAD) patients (14 males, mean age 46 ± 10 years) were confronted with the stroop test, during which salivary-α-amylase (sAA), salivary cortisol, and heart rate variability (HRV) were assessed. The results showed that stroop test as a stressor induced autonomic nervous response in GAD patients, which was mainly manifested as the increase in HRV representing sympathetic nervous system and the decrease in HRV representing vagal nerve activity. Moreover, the basic function of sympathetic-adrenal medulla system was hyperfunctional in GAD patients while theirs reactivity was limited, which showed the more serious the lesion was, the higher the baseline value of sAA was, and the less sAA secretion increase would be, or even decrease after mental stress. The change of sAA after stroop test in GAD patients can predict the severity of anxiety, but subjective psychological perception can not.

Consistency of Positron Emission Tomography and Myocardial Contrast Echocardiography in Diagnosing Mental Stress-Induced Myocardial Ischemia: Study Protocol of a Prospective Study-Background, Design and Method.

Mental stress-induced myocardial ischemia (MSIMI) has attracted increasing attention in the last 30 y. Positron emission tomography/computed tomography (PET/CT) is among the most accurate methods for evaluating myocardial perfusion. Even so, echocardiography seems to be a more harmless option when the radiation exposure and high expense of PET/CT are considered. To date, no previous studies have compared the consistency between echocardiography and PET/CT in the diagnosis of MSIMI. The primary aim of this research was to compare the consistency of myocardial contrast echocardiography and PET/CT in diagnosing MSIMI in women with angina symptom/ischemia but no obstructive coronary artery disease (INOCA). Fifty adult female patients with INOCA were recruited for a 12-min-long mental stress test. Each patient underwent both echocardiography and PET/CT at baseline and during mental stress testing; the interval between the two examinations was 1-3 d and the sequence was assigned naturally. MSIMI is defined by a summed difference score (SDS) ≥3 on PET-CT during mental stress testing. It is also defined by new abnormal wall motion, ejection fraction reduction ≥5%, and/or development of ischemic ST change on the electrocardiogram during mental stress testing. This study examined the consistency of PET/CT and myocardial contrast echocardiography in diagnosing MSIMI.

MicroRNA-92b-3p suppresses angiotensin II-induced cardiomyocyte hypertrophy via targeting HAND2.

AIMS: The pathological cardiac hypertrophy will develop into heart failure, which has no effective treatment currently. Previous studies have proved that microRNAs (miRNAs) participate in the development of cardiac hypertrophy and regulate the pathological progress. In this study, we want to investigate the role of microRNA-92b-3p (miR-92b-3p) in cardiomyocyte hypertrophy and the mechanisms involved. MATERIALS AND METHODS: Neonatal mouse ventricular cells (NMVCs) were isolated from the hearts of 1-3-d-old newborn C57BL6 mice. The isolated NMVCs were induced hypertrophic phenotype by Angiotensin-II (Ang-II) and the cell size was examined by FITC-phalloidin staining assay. The expression of miR-92b-3p was determined by quantitative real-time PCR (qRT-qPCR). MRNA and protein level of ß-MHC, ACTA1 and HAND2 in NMVCs transfected with miR-92b-3p mimic and inhibition were assessed by RT-qPCR assay and western blot assay, respectively. Dual luciferase assay was used to verify the interaction between miR-92b-3p and the 3'-untranslated region (UTR) of HAND2 gene. KEY FINDINGS: MiR-92b-3p and HAND2 were significantly increased in Ang-II-induced NMVCs. Overexpression of miR-92b-3p can ameliorate Ang-II-induced cardiomyocyte hypertrophy. MiR-92b-3p negatively regulated HAND2 expression at the transcriptional level. Both miR-92b-3p mimic and HAND2 siRNA could efficiently inhibit Ang-II-induced hypertrophy in mouse cardiomyocytes. SIGNIFICANCE: MiR-92b-3p inhibits Ang-II-induced cardiomyocyte hypertrophy via targeting HAND2.

Targeting myocyte-specific enhancer factor 2D contributes to the suppression of cardiac hypertrophic growth by miR-92b-3p in mice.

The role of microRNA-92b-3p (miR-92b-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-92b-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. MiR-92b-3p was markedly decreased in the myocardium of Ang-II-infused mice and of patients with cardiac hypertrophy. However, miR-92b-3p expression was revealed increased in Ang-II-induced neonatal mouse cardiomyocytes. Cardiac hypertrophy was shown attenuated in Ang-II-infused mice received tail vein injection of miR-92b-3p mimic. Moreover, miR-92b-3p inhibited the expression of atrial natriuretic peptide (ANP), skeletal muscle α-actin (ACTA1) and ß-myosin heavy chain (MHC) in Ang-II-induced mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2D (MEF2D), which was increased in Ang-II-induced mouse hypertrophic myocardium and cardiomyocytes, was identified as a target gene of miR-92b-3p. Functionally, miR-92b-3p mimic, consistent with MEF2D siRNA, inhibited cell size increase and protein expression of ANP, ACTA1 and ß-MHC in Ang-II-treated mouse cardiomyocytes. Taken together, we demonstrated that MEF2D is a novel target of miR-92b-3p, and attenuation of miR-92b-3p expression may contribute to the increase of MEF2D in cardiac hypertrophy.

Prevalence and determinants of left ventricular geometric abnormalities in hypertensive patients: A study based on the updated classification system of left ventricular geometry.

OBJECTIVE: This study was to determine whether different risk factors were associated with different type of left ventricular (LV) geometric abnormalities. METHODS: This retrospective analysis included 2290 hypertensive participants without other cardiovascular disease, valve disease and with ejection fraction ≥50%. The type of LV geometric abnormality was defined on the basis of the new classification system. RESULTS: LV geometric abnormalities were detected in 1479 subjects (64.6%), wherein concentric LV remodeling is the most common LV geometric abnormality (40.3%). Large waist circumference (WC) and neck circumference (NC) were positively associated with concentric LV remodeling, whereas body mass index (BMI) [odds ratio (OR) 0.89, 95% CI 0.85∼0.92, P ＜ 0.001] and systolic blood pressure (SBP) (OR 0.99, 95% CI 0.98∼0.99, P = 0.018) were inversely associated with concentric abnormalities. SBP and age were positively associated with eccentric dilated LVH, while male was inversely associated with eccentric dilated left ventricular hypertrophy (LVH). Age was the strongest risk factor for eccentric dilated LVH (OR 1.05, 95% CI 1.03∼1.07, P ＜ 0.001). Age, NC, SBP, hyperuricemia, and alcohol use were positively associated with concentric LVH, whereas BMI (OR 0.95, 95% CI 0.90∼0.99, P = 0.033) and male (OR 0.12, 95% CI 0.07∼0.18, P ＜ 0.001) were negatively associated with concentric LVH. CONCLUSION: The prevalence of hypertensive LV geometric abnormality in rural area of Southern China was obvious higher. Compared with eccentric LV geometric abnormalities, there were more risk factors, including large WC and NC, age, NC, SBP, hyperuricemia, alcohol use, BMI and gender, which were associated with concentric LV geometric abnormalities.