Exosomal CircRNAs in Circulation Serve as Diagnostic Biomarkers for Acute Myocardial Infarction.

BACKGROUND: The diagnostic potential of circular RNAs (circRNAs) in circulating exosomes for acute myocardial infarction (AMI) is not well understood, despite existing research indicating their role in cardiovascular diseases. This study aimed to clarify the significance of exosomal circular RNAs as indicators for AMI. METHODS: We examined 120 individuals diagnosed with AMI and 83 individuals with non-cardiogenic chest pain (NCCP), all previously enrolled in a conducted study. High-throughput sequencing to identify differentially expressed circRNAs in the circulating exosomes of AMI patients. To validate, we employed Real-Time polymerase chain reaction (RT-PCR) targeting five circRNAs that exhibited notable increase. RESULTS: The sequencing identified 893 exosomal circRNAs with altered expression in AMI patients, including 118 up-regulated and 775 down-regulated circRNAs. Genes linked to these circRNAs were enriched in crucial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, highlighting their direct relevance to AMI pathophysiology. Three exosomal circRNAs (hsa_circ_0001558, hsa_circ_0001535, and hsa_circ_0000972) showed significant up-regulation in AMI patients during the initial validation cohort. The corresponding area under the curve (AUC) values were 0.79, 0.685, and 0.683, respectively. Further validation of hsa_circ_0001558 in a second cohort showed a 4.45-fold increase in AMI patients, with AUC = 0.793. The rise was particularly noticeable in patients with non-ST-elevation myocardial infarction (NSTEMI) (2.80 times, AUC = 0.72) and patients with ST-elevation myocardial infarction (STEMI) (5.27 times, AUC = 0.831) compared to patients with NCCP. CONCLUSIONS: Our findings demonstrate significant differences in the expression patterns of circRNAs in plasma exosomes between AMI patients and NCCP patients. Specifically, hsa_circ_0001558 appears as a promising indicator for AMI diagnosis. Further research is necessary to fully evaluate the diagnostic potential of exosomal circRNAs in the context of AMI, emphasizing the importance of these findings.

Effectiveness of Heart Failure Checklist Management in Patients with Chronic Heart Failure: An Open-Label, Single-Center Controlled Study During 18 Months of Follow-Up.

Background: The efficacy of chronic heart failure (CHF) checklist management in reducing adverse outcomes of heart failure patients is still uncertain. This study explores whether CHF checklist management is more useful than usual care in reducing adverse health outcomes in the medium- and long-term among CHF patients. Methods: In our prospective study, 132 patients with CHF were randomly assigned to CHF management group and usual care group by random number method. Patients in CHF management group were conducted through CHF checklist by cardiologists and general practitioner. Patients assigned to usual care were treated by non-stationary medical group without checklist. All groups were followed up for 18 months. Results: There was no significant difference in overall mortality rate between management group and control group during 18 months (12.3% [8/65] vs. 11.7% [7/60], P = 0. 912]). The re-hospitalization rate of heart failure in management group (18.5% [12/65]) was significantly lower than that in usual care group (38.3% [23/60]) after 18 months of follow-up (P = 0.013). Median NT-proBNP level (632.3 ng/l vs. 1678 ng/l, p = 0.004) was lower in management group than that in usual care group. Cardiac ultrasonography was performed at 18 months between the management and usual care group. LVEDD (55.88±7.11 mm vs. 60.92±8.06 mm) and LVESD (43.25±8.42mm vs. 48.41± 9.02mm) were decreased (P<0.01). LVEF was increased (45.36±10.64% vs. 39.96 ±10.15%, P<0.01). The utilization rate of ACEI/ARB/ARNI, ß-blocker were high in management group. Conclusion: CHF checklist management by cardiologists and general practitioners can significantly reduce the re-hospitalization and improve cardiac function. CHF management through heart failure checklist may improve prognosis in patients with CHF in the medium- and long-term.

Circulating Exosomal CircRNAs as Diagnostic Biomarkers for Chronic Coronary Syndrome.

Circular RNA (circRNA) has been reported to be involved in the pathogenesis of cardiovascular disease; however, it is unclear whether circRNA carried by exosomes (exos) can be used as biomarkers for chronic coronary syndrome (CCS). High-throughput sequencing was carried out in the plasma exosomal RNA of 15 CCS patients and 15 non-cardiac chest pain patients (NCCP, control group) to screen for differentially expressed circRNAs. Selected differentially expressed exo-circRNAs were further verified by real-time polymerase chain reaction in a small-sample cohort and a large-sample cohort. A total of 276 circRNAs were differentially expressed in the plasma exosomes of CCS patients, with 103 up-regulated and 173 down-regulated. Among the 103 up-regulated circRNAs, 5 circRNAs with high expression levels were selected for validation. Real time quantitative PCR of the first and second validation cohort demonstrated that exo-hsa_circ_0075269 and exo-hsa_circ_0000284 were significantly up-regulated in patients with CCS. Circulating exo-hsa_circ_0075269 and exo-hsa_circ_0000284 yielded the area under the curve values of 0.761 (p < 0.001, 95%CI = 0.669, 0.852) and 0.623 (p = 0.015, 95%CI = 0.522, 0.724) for CCS, respectively, by ROC curve analysis. In conclusion, the expression profile of circRNA in plasma exosomes of patients with CCS was significantly different from that of the control group. Plasma exo-hsa_circ_0075269 and exo-hsa_circ_0000284 have the potential to be new biomarkers for CCS.

99mTc-HFAPi imaging identifies early myocardial fibrosis in the hypertensive heart.

BACKGROUND: This study aimed to explore whether 99mTc-radiolabeled fibroblast activation protein inhibitor (99mTc-HFAPi) imaging can detect early myocardial fibrosis in the hypertensive heart. METHODS: In the experimental model, spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto rats (WKYs) were randomly divided into three groups (8, 16, and 28 weeks). The animals underwent 99mTc-HFAPi imaging and echocardiography. Autoradiography and histological analyses were performed in the left ventricle. The mRNA and protein expression level of the fibroblast activation protein (FAP) and collagen I were measured using quantitative PCR and western blot. In the clinical investigation, a total of 106 patients with essential hypertension and 20 gender-matched healthy controls underwent 99mTc-HFAPi imaging and echocardiography. RESULTS: In-vivo and in-vitro autographic images demonstrated diffusely enhanced 99mTc-HFAPi uptake in the SHR heart starting at week 8, before irreversible collagen deposition. The mRNA and protein levels of FAP in SHRs began to increase from week 8, whereas changes in collagen I levels were not detected until week 28. In the clinical investigation, even in hypertensive patients with normal diastolic indicators, normal left ventricular geometry, and normal global longitudinal strain (GLS), the prevalence of increased 99mTc-HFAPi uptake reached 34, 41, and 20%, respectively, indicating that early fibrogenesis precedes structural and functional myocardial abnormalities. CONCLUSION: In hypertension, 99mTc-HFAPi imaging can detect early fibrotic process before myocardial functional and structural changes.

Ezrin regulates the progression of NSCLC by YAP and PD-L1

Purpose To determine whether ezrin regulates Yes-associated protein (YAP) and programed cell death ligand-1 (PD-L1), which are involved in the invasion and metastasis of non-small cell lung cancer (NSCLC). Methods Immunohistochemistry of 164 NSCLC and 16 para-cancer tissues was performed to detect ezrin, YAP, and PD-L1 expression. Further, H1299 and A549 cells were transfected with lentivirus, and then colony formation, CCK8, transwell, and wound-healing assays were used to assess cell proliferation, migration, and invasion. RT-qPCR and western blotting were used for quantitative analysis of ezrin, PD-L1, and YAP expression. Moreover, the role of ezrin in tumor growth was assessed in vivo, and immunohistochemistry and western blotting were performed to evaluate changes in ezrin expression in mouse samples. Results The positive protein expression rates of these molecules in NSCLC were as follows: ezrin, 43.9% (72/164); YAP, 54.3% (89/164); and PD-L1, 47.6% (78/164); these were higher than those in normal lung tissues. Moreover, YAP and ezrin expression positively correlated with PD-L1 expression. Ezrin promoted proliferation, migration, invasion, and expression of YAP and PD-L1in NSCLC. Inhibition of ezrin expression reduced the effects of ezrin on cell proliferation, migration, invasion, inhibited the expression of YAP and PD-L1, and obviously reduced experimental tumor volume in vivo. Conclusions Ezrin is overexpressed in NSCLC patients and correlates with PD-L1 and YAP expression. Ezrin regulates YAP and PD-L1 expression. Inhibition of ezrin delayed NSCLC progression (AU)

SGLT2i alleviates epicardial adipose tissue inflammation by modulating ketone body-glyceraldehyde-3-phosphate dehydrogenase malonylation pathway.

AIMS: Inflammation in the epicardial adipose tissue (EAT) is a contributor to atrial fibrillation. Studies have reported that sodium glucose co-transporter 2 inhibitor (SGLT2i) can alleviate EAT inflammation. However, the mechanism remains elusive. This study aims to investigate the molecular mechanism of SGLT2i in reducing EAT inflammation and to explore the effects of SGLT2i on atrial fibrosis in atrial fibrillation. METHODS: Sprague-Dawley rats were injected with angiotensin II to induce atrial fibrillation and randomly assigned to receive SGLT2i ( n  = 6) or vehicle ( n  = 6). Macrophages (RAW264.7) were treated with ketone bodies; ACC1 knockdown/overexpression and malonyl-CoA overexpression were performed in vitro . The levels of inflammatory cytokines, ACC1, and malonyl-CoA were examined by ELISA. GAPDH malonylation was measured by co-immunoprecipitation. RESULTS: In atrial fibrillation rats, SGLT2i increased the ketone body levels and decreased the expression of ACC1 and alleviated EAT inflammation and atrial fibrosis. In RAW264.7 cells, ketone bodies decreased the levels of ACC1, malonyl-CoA, and GAPDH malonylation, accompanied by reduced inflammatory cytokines. ACC1 knockdown decreased the expression of malonyl-CoA and GAPDH malonylation and alleviated lipopolysaccharide (LPS)-induced macrophage inflammation; these effects were inhibited by malonyl-CoA overexpression. Furthermore, the protective effects of ketone bodies on macrophage inflammation were abrogated by ACC1 overexpression. CONCLUSION: SGLT2i alleviates EAT inflammation by reducing GAPDH malonylation via downregulating the expression of ACC1 through increasing ketone bodies, thus attenuating atrial fibrosis.

Circulating exosomal lncRNAs in patients with chronic coronary syndromes.

Introduction: The concept of chronic coronary syndrome (CCS) was first presented at the European Society of Cardiology Meeting in 2019. However, the roles of exosomal lncRNAs in CCS remain largely unclear. Material and methods: A case-control study was performed with a total of 218 participants (137 males and 81 females), including 15 CCS patients and 15 controls for sequencing profiles, 20 CCS patients and 20 controls for the first validation, and 100 CCS patients and 48 controls for the second validation. Exosomes were isolated from the plasma of CCS patients and controls, and exosomal lncRNAs were identified by sequencing profiles and verified twice by qRT-PCR analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of exosomal lncRNAs for CCS patients. Results: A total of 152 significantly differentially expressed lncRNAs with over two-fold changes were detected in plasma exosomes of CCS patients, including 90 upregulated and 62 downregulated lncRNAs. Importantly, 6 upregulated lncRNAs with the top fold changes were selected for validations. Exosomal lncRNAs ENST00000424615.2 and ENST00000560769.1 were significantly elevated in CCS patients in both validations compared with controls. The areas under the ROC of lncRNAs ENST00000424615.2 and ENST00000560769.1 were 0.654 and 0.722, respectively. Additionally, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels (p = 0.028). Conclusions: Exosomal lncRNA ENST00000424615.2 and ENST00000560769.1 were identified as novel diagnosis biomarkers for patients with CCS. Moreover, exosomal lncRNA ENST00000560769.1 was significantly higher in the CCS patients with more diseased vessels, and might be associated with a poor prognosis.

Ezrin regulates the progression of NSCLC by YAP and PD-L1.

PURPOSE: To determine whether ezrin regulates Yes-associated protein (YAP) and programed cell death ligand-1 (PD-L1), which are involved in the invasion and metastasis of non-small cell lung cancer (NSCLC). METHODS: Immunohistochemistry of 164 NSCLC and 16 para-cancer tissues was performed to detect ezrin, YAP, and PD-L1 expression. Further, H1299 and A549 cells were transfected with lentivirus, and then colony formation, CCK8, transwell, and wound-healing assays were used to assess cell proliferation, migration, and invasion. RT-qPCR and western blotting were used for quantitative analysis of ezrin, PD-L1, and YAP expression. Moreover, the role of ezrin in tumor growth was assessed in vivo, and immunohistochemistry and western blotting were performed to evaluate changes in ezrin expression in mouse samples. RESULTS: The positive protein expression rates of these molecules in NSCLC were as follows: ezrin, 43.9% (72/164); YAP, 54.3% (89/164); and PD-L1, 47.6% (78/164); these were higher than those in normal lung tissues. Moreover, YAP and ezrin expression positively correlated with PD-L1 expression. Ezrin promoted proliferation, migration, invasion, and expression of YAP and PD-L1in NSCLC. Inhibition of ezrin expression reduced the effects of ezrin on cell proliferation, migration, invasion, inhibited the expression of YAP and PD-L1, and obviously reduced experimental tumor volume in vivo. CONCLUSIONS: Ezrin is overexpressed in NSCLC patients and correlates with PD-L1 and YAP expression. Ezrin regulates YAP and PD-L1 expression. Inhibition of ezrin delayed NSCLC progression.

Thrombospondin-1 plasma levels associated with in-hospital major adverse cardiovascular events in patients with acute coronary syndrome.

BACKGROUND: Thrombospondin-1, a large matricellular glycoprotein, exerts multifaced biological effects on the cardiovascular system and is correlated with cardiovascular diseases. Its plasma levels and correlation with in-hospital prognosis are yet unclear in the acute coronary syndrome population. The present study aimed to evaluate the correlation between thrombospondin-1 plasma levels and in-hospital adverse events in patients with acute coronary syndrome. METHODS: This is a cross-sectional study. A total of 341 inpatients with acute coronary syndrome were recruited in Beijing Chaoyang Hosipital from May 2021 to November 2021. The thrombospondin-1 plasma levels were measured, and the in-hospital major adverse cardiovascular events, including all-cause death, recurrent ischemia, arrhythmias, and heart failure, were recorded. This correlation was assessed by logistic regression analysis. RESULTS: The thrombospondin-1 plasma levels were higher in patients with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction compared to those in unstable angina (P < 0.001), while the differences between the two different types of myocardial infarction were not statistically different. Thrombospondin-1 plasma levels were correlated with GRACE score, leukocytes, neutrophils, platelets, troponin I, creatine kinase-MB, D-dimer, C-reactive protein, erythrocyte sedimentation rate, and log10 brain natriuretic peptide. Furthermore, thrombospondin-1 plasma levels were associated with the in-hospital major adverse cardiovascular events in patients with acute coronary syndrome (P = 0.001). CONCLUSIONS: Thrombospondin-1 plasma levels were higher in patients with myocardial infarction than those in unstable angina. The high thrombospondin-1 plasma levels were associated with in-hospital major adverse cardiovascular events.

The mediating role of anxiety and depression in the relationship between coping styles and life satisfaction among frontline medical workers during the COVID-19 pandemic: A cross-sectional study.

This study aimed to examine the mediating role of anxiety and depression in the relationship between coping styles and life satisfaction among frontline medical workers during the COVID-19 pandemic. Five hundred and fourteen frontline medical workers from Zunyi were recruited to complete questionnaires, including the Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Satisfaction with Life Scale (SWLS), and Simplified Coping Style Questionnaire (SCSQ). SPSS 24.0 was used to measure the characteristics of anxiety, depression, life satisfaction, and coping styles. We found that the prevalence rates of anxiety and depression among study participants were 22.57% and 18.29%, respectively. Besides, anxiety was positively correlated with depression; anxiety and depression were positively correlated with passive coping style but negatively correlated with life satisfaction and active coping style; life satisfaction was positively correlated with active coping style and negatively correlated with passive coping style (all p < 0.001). Moreover, anxiety and depression mediated the relationship between coping styles and life satisfaction. Anxiety accounted for 18.6% of the effect of active coping style and 35.48% of the effect of passive coping style on life satisfaction. Depression accounted for 48.84% of the effect of active coping style and 67.74% of the effect of passive coping style on life satisfaction. The present study provides novel insights into the effect of subclinical anxiety and depression on frontline medical workers in the pandemic area. Anxiety and depression yielded a mediating effect on the relationship between coping styles and life satisfaction.

A Preliminary Study on the Value of Intestinal Flora in Predicting Major Adverse Cardiovascular and Cerebrovascular Events in Patients with Refractory Hypertension.

Objective: To investigate the value of intestinal flora in predicting major adverse cardiovascular and cerebrovascular events (MACCE) in patients with refractory hypertension (RH). Methods: 359 patients with RH hospitalized in our hospital from April 2020 to March 2021 were followed up for 1 year and selected for the study. These patients were divided into a MACCE group and no-MACCE group. Results were analyzed by comparing general information, the abundance of intestinal flora at the phylum level, and the abundance of intestinal flora at the species level between the two groups. The influence factors related to MACCE were evaluated using multifactor logistic regression analysis, and the value of intestinal flora in predicting MACCE was determined using receiver operating characteristic (ROC) and the area under ROC (AUC). Results: Systolic blood pressure was higher in the MACCE group than in the no-MACCE group (P < 0.05). The abundances of Actinomycetes and Verrucomicrobia were higher in the MACCE group than in the no-MACCE group, while unnamed viruses were the opposite (P < 0.05). The abundances of Eubacterium eligens, Akkermansia muciniphila, Prevotella stercorea, and Eubacterium rectale were lower in the MACCE group than in the no-MACCE group, while Escherichia coli, Clostridium hathewayi, and Ruminococcus gnavus were opposite (P < 0.05). Systolic blood pressure, Actinomycetes, unnamed viruses, Verrucomicrobia, Eubacterium eligens, Akkermansia muciniphila, Prevotella stercorea, Eubacterium rectale, Escherichia coli, Clostridium hathewayi, and Ruminococcus gnavus were closely associated with MACCE in RH patients (P < 0.05). In addition, Akkermansia muciniphila had the highest AUC among the single indicator but was still lower than the AUC of the combined detection. Conclusion: The increases of Actinomycetes, Verrucomicrobia, Escherichia coli, Clostridium hathewayi, and Ruminococcus gnavus and the decreases of unnamed viruses, Eubacterium eligens, Akkermansia muciniphila, Prevotella stercorea, and Eubacterium rectale were associated with MACCE in RH patients, and the combined detection may provide a method and idea for predicting and preventing MACCE.

Activation of PI3k/Akt/mTOR Signaling Induces Deposition of p-tau to Promote Aluminum Neurotoxicity.

Aluminum neurotoxicity impairs learning and memory ability, but the molecular mechanism has not been elucidated. The aim of this study was to examine the role of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling in regulating the expression of synaptic plasticity-related proteins (PRPs) and p-tau deposition to explore the mechanism underlying aluminum-induced neurotoxicity. We constructed a sub-chronic aluminum-exposed Sprague Dawley (SD) rat model to assess aluminum neurotoxicity in vivo. The learning and memory abilities of rats were examined using the Morris water maze test. We also assessed the effect of aluminum in vitro using rat pheochromocytoma (PC12) cells. To explore the role of PI3K/Akt/mTOR signaling in aluminum neurotoxicity, we used the PI3K inhibitor wortmannin and the mTOR inhibitor rapamycin in aluminum-treated PC12 cells. Protein expression was examined by western blotting. Aluminum disrupted the learning and memory abilities of SD rats. Mechanistically, aluminum reduced the levels of the synaptic PRPs (cAMP-response element binding protein (CREB), glutamate receptor 1 (GluR1), glutamate receptor 2 (GluR2), and postsynaptic density protein 95 (PSD-95), and it increased p-tau deposition in the hippocampus of SD rats. We observed similar results in aluminum-treated PC12 cells. Further, PI3K/Akt/mTOR signaling was abnormally activated in aluminum-treated PC12 cells, and treatment with rapamycin reversed the decrease in synaptic PRPs levels and the increase in p-tau deposition. In conclusion, the activation of PI3K/Akt/mTOR signaling reduces the levels of synaptic PRPs and increases p-tau deposition induced by aluminum. Therefore, the PI3K/Akt/mTOR pathway participates in the mechanism of aluminum neurotoxicity.

Sirtuin 7 serves as a promising therapeutic target for cardiorenal diseases.

Cardiovascular disorders and associated renal diseases account for the main cause of morbidity and mortality worldwide, necessitating the development of novel effective approaches for the prevention and treatment of cardiorenal diseases. Mammalian sirtuins (SIRTs) function as nicotinamide adenine dinucleotide (NAD+)-dependent protein/histone deacetylases. Seven members of SIRTs share a highly invariant catalytic core domain responsible for the specific enzymatic activity. Intriguingly, the broad distribution of SIRTs and alternative isoforms implicate its distinct functions in diverse cardiac and renal cells and tissue types. Notably, SIRT7 has been shown to exert beneficial effects in cardiorenal physiology and pathophysiology via modulation of senescence, DNA damage repair, ribosomal RNA synthesis, protein biosynthesis, angiogenesis, apoptosis, superoxide generation, cardiorenal metabolism, and dysfunction. Furthermore, SIRT7 has emerged as a critical modulator of a broad range of cellular activities including oxidative stress, inflammation response, endoplasmic reticulum stress, and mitochondrial homeostasis, which are all of great significance in postponing the progression of cardiorenal diseases. More importantly, SIRT7 has been implicated in cardiorenal hypertrophy, fibrosis, remodeling, heart failure, atherosclerosis as well as renal acid-base and electrolyte homeostasis as an essential regulator. In this article, we focus on the involvement in cardiorenal physiology and pathophysiology, diverse actions and underlying mechanisms of the SIRT7 signaling, highlighting its updated research progress in heart failure, atherosclerosis, diabetic nephropathy and other cardiorenal diseases. Targeting SIRT7 signaling could be potentially exploited as a therapeutic strategy aiming to prevent and treat cardiorenal diseases.

Elevated Plasma Thymic Stromal Lymphopoietin After Acute Myocardial Infarction.

Background: Thymic stromal lymphopoietin (TSLP), a distant paralog of the cytokine IL-7, has been shown to be associated with atherosclerosis. However, the effect of plasma TSLP level after acute myocardial infarction (AMI) remains largely unclear. Thus, we aimed to assess the relationship between the concentration of TSLP at admission and the risk of major adverse cardiovascular events (MACE) in AMI patients. Methods: A total of 175 patients with AMI and 145 unstable angina (UA) controls were recruited in the present study. The clinical characteristics were collected, and MACE was recorded during hospitalization and the follow-up period after discharge. Results: The median value (25, 75 percentiles) of TSLP concentrations in the AMI group was higher than that in the UA group [11.18 (8.14-15.22) vs. 8.56 (5.26-11.94) pg/ml, p < 0.001, respectively]. Multivariate linear regression analysis revealed that Troponin-I (standardized ß = 0.183, p = 0.004) was an independent factor for TSLP. According to the median of TSLP concentrations, all the AMI patients were divided into the high-level group (TSLP level ≥ 11.18 pg/ml, N = 91) and the low-level group (TSLP <11.18 pg/ml, N = 84). In a receiver operating characteristic curve analysis, the area under the curve for TSLP as a predictor of AMI was 0.674 with a cut-off value of 9.235 pg/ml. After a median follow-up of 14 months, Kaplan-Meier survival analysis showed no significant difference in MACE-free survival between the two groups (p = 0.648). Finally, the multivariate logistic regression analyses demonstrated that TSLP was a negative predictor of MACE in AMI patients (OR:0.778,95% CI:0.733-0.876, p = 0.032). Conclusions: Plasma TSLP levels were elevated in patients with AMI than those in UA. The lower TSLP concentration was associated with MACE after AMI.

Evolving roles of cardiac fibroblasts in cardiogenesis and immunology, electrophysiology, and aging.

Cardiac fibroblasts (CFs), one of the major groups of cardiac cells, play a prominent role in the cardiac microenvironment through communicating with other cells such as cardiomyocytes, endothelial cells and immune cells. These communications are required not only during cardiac development but also during pathogenesis. CFs are also involved in developmental changes in the post-natal and pre-natal heart through depositing extra cellular matrix (ECM) and maintaining cardiac tissue structure. Furthermore, CFs show both detrimental and beneficial effects in maintenance of the electrophysiology of the heart. Senescent CFs in the cardiac microenvironment influence other cardiac cells through paracrine signaling, which would worsen or cure the diseases. Therefore, there is a need of exclusive study on CFs' role in the developmental stage of the heart, electrophysiology, and senescence. This review discusses the current research about CFs' function, especially the CFs' role in cardiac development, electrophysiology, and senescence, and proposes a certain gap filling future prospective.

Declined ELABELA plasma levels in hypertension patients with atrial fibrillation: a case control study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients with hypertension. ELABELA, which has cardioprotective effects, is decreased in the plasma of patients with hypertension and might be associated with AF in the hypertensive population. This study aims to measure the ELABELA plasma levels in hypertension patients with and without AF and to analyse the related factors. METHODS: A total of 162 hypertension patients with or without AF were recruited for our monocentric observational study. Subjects were excluded if they had a history of valvular heart disease, rheumatic heart disease, cardiomyopathy, thyroid diseases, or heart failure. The patients' histories were recorded, and laboratory examinations were conducted. Plasma ELABELA was detected by immunoassay. Echocardiographs were performed, and parameters were collected by two experienced doctors. Binary logistic regression analysis was used to identify the association between ELABELA plasma level and AF in patients with hypertension. RESULTS: Plasma ELABELA levels were lower in hypertension patients with AF than in those without AF (2.0 [1.5, 2.8] vs. 4.0 [3.4, 5.0] ng/ml, P < 0.001). ELABELA levels were correlated with age, heart rate, BNP levels and left atrial dimension. In addition to the left atrial dimension, ELABELA plasma levels were associated with AF in patients with hypertension (OR 0.081, 95% CI 0.029-0.224, P < 0.001). ELABELA levels were further decreased in the persistent AF subgroup compared with the paroxysmal AF subgroup (1.8 [1.4, 2.5] vs. 2.2 [1.8, 3.0] ng/ml, P = 0.012) and correlated with HR, BNP and ESR levels. CONCLUSIONS: ELALABELA levels were decreased in hypertension patients with AF and further lowered in the persistent AF subgroup. Decreased ELABELA plasma levels were associated with AF in hypertension patients and may be an underlying risk factor.

Does taking an angiotensin inhibitor increase the risk for COVID-19? - a systematic review and meta-analysis.

Because SARS-COV2 entry into cells is dependent on angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) increase ACE2 activity, the safety of ACEI/ARB usage during the coronavirus disease 2019 (COVID-19) pandemic is a controversial topic. To address that issue, we performed a meta-analysis following The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches of the Embase, MEDLINE, PubMed, and Cochrane Library databases identified 16 case-control studies examining the effect of ACEI/ARB on the incidence of COVID-19 and its severity. ACEI/ARB usage was associated with an increased risk of COVID-19 morbidity (odds ratio (OR) 1.20, 95% confidence interval (CI) 1.07-1.33, P=0.001) among the general population but not in a hypertensive population (OR 1.05, 95% CI 0.90-1.21, P=0.553). ACEI/ARB usage was not associated with an increased risk of COVID-19 morbidity (coefficient 1.00, 95% CI 1.00-1.00, P=0.660) when we adjusted for hypertension in the general population. ACEI/ARB usage was also not associated with an increased risk of severe illness (OR 0.90, 95%CI 0.55-1.47, P=0.664) or mortality (OR 1.43, 95%CI 0.97-2.10, P=0.070) in COVID-19 patients. Our meta-analysis revealed that ACEI/ARB usage was not associated with either the increased risk of SARS-COV2 infection or the adverse outcomes in COVID-19 patients.

Lower Plasma Elabela Levels in Hypertensive Patients With Heart Failure Predict the Occurrence of Major Adverse Cardiac Events: A Preliminary Study.

Background: Elabela, a novel cardiac developmental peptide, has been shown to improve heart dysfunction. However, the roles and correlation of Elabela in predicting adverse cardiac events in hypertensive patients with heart failure (HF) remain largely unclear. Objective: To measure plasma levels of Elabela in hypertensive patients with HF and evaluate its prognostic value. Methods: A single-site, cohort, prospective, observational study was investigated with all subjects, including control subjects and hypertensive patients with or without HF, whom were recruited in Beijing Chaoyang Hospital Affiliated to Capital Medical University form October 2018 to July 2019. The subjects among different groups were matched based on age and sex. The clinical characteristics were collected, and plasma Elabela levels were detected in all subjects. The hypertensive patients with HF were followed up for 180 days, and the major adverse cardiac events (MACE) were recorded. The Cox regression was used to explore the correlation between Elabela level and MACE in hypertensive patients with or without HF. The receiver operating characteristic curves were used to access the predictive power of plasma Elabela level. Results: A total of 308 subjects, including 40 control subjects, 134 hypertensive patients without HF, and 134 hypertensive patients with HF were enrolled in this study. Plasma levels of Elabela were lower in hypertensive patients compared with control subjects [4.9 (2.8, 6.7) vs. 11.8 (9.8, 14.0) ng/ml, P < 0.001]. Furthermore, HF patients with preserved ejection fraction had a higher plasma Elabela level than those with impaired left ventricular systolic function (heart failure with mid-range ejection fraction and heart failure with reduced ejection fraction). The hypertensive patients with HF and higher plasma Elabela levels had a better readmission-free and MACE-free survival than those with lower plasma Elabela levels in survival analysis. The Cox regression analysis revealed that plasma Elabela levels were negatively associated with MACE (HR 0.75, 95% CI 0.61-0.99, P = 0.048) in hypertensive patients with HF. Conclusion: Plasma Elabela levels were decreased in hypertensive patients with left ventricular systolic dysfunction. Thus, Elabela may be potentially used as a novel predictor for MACE in hypertensive patients with HF.

Genetic deletion of CMG2 exacerbates systemic-to-pulmonary shunt-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD-PAH) with systemic-to-pulmonary shunt (SPS) is characterized by proliferative vascular remodeling. Capillary morphogenesis gene-2 (CMG2) plays a key role in cell proliferation and apoptosis. This study aimed to determine the role of CMG2 in the pathogenesis of SPS-induced PAH. CMG2 levels were significantly downregulated in pulmonary arterioles from patients with Eisenmenger syndrome and rats with SPS-induced PAH. CMG2 was highly expressed in several cells including human pulmonary arterial smooth muscle cells (HPASMCs). CMG2-/- rats exhibited more severe PAH and pulmonary vascular remodeling than wild-type rats when exposed to SPS for 8 weeks. Overexpression of CMG2 significantly inhibited proliferation and promoted apoptosis of HPASMCs, while knockdown of CMG2 promoted cell proliferation and inhibited cell apoptosis. Next-generation sequencing and subsequent validation results suggested that PI3K-AKT was the most prominent signaling pathway regulated by differentially expressed genes (DEGs) in CMG2-/- rat lungs. Our work identified a novel role for CMG2 in SPS-induced PAH based on the findings that CMG2 deficiency exacerbates SPS-induced vascular remodeling in the development of PAH, indicating that CMG2 might act as a potential target for the treatment of CHD-PAH.