lncRNA-056298 Regulates GAP43 and Promotes Cardiac Intrinsic Autonomic Nerve Remodelling in a Canine Model of Atrial Fibrillation Induction after Ganglionated Plexus Ablation.

BACKGROUND: Cardiac intrinsic autonomic nerve remodelling has been reported to play an important role in the recurrence of atrial fibrillation after radiofrequency ablation, which significantly affects the long-term efficacy of this procedure. lncRNAs have been shown to interact in the pathological processes underlying heart diseases. However, the roles and mechanisms of lncRNAs in cardiac intrinsic autonomic nerve remodelling during atrial fibrillation reduction after ganglionated plexus ablation remain unknown. OBJECTIVES: The aim of this study was to investigate the mechanism by which lncRNA- 056298 modulates GAP43 to affect cardiac intrinsic autonomic nerve remodelling and facilitate the induction of atrial fibrillation after ganglionated plexus ablation. METHODS: A canine model of right atrial ganglionated plexus ablation was established. The atrial electrophysiological characteristics and neural markers were detected before and after 6 months of ganglionated plexus ablation. High-throughput sequencing was used to screen differentially expressed lncRNAs in target atrial tissues, and lncRNA- 056298 was selected to further explore its effects and mechanisms on cardiac intrinsic autonomic nerve remodelling. RESULTS: The induction rate of atrial fibrillation increased in dogs after ganglionated plexus ablation. Overexpression of lncRNA-056298 by lentivirus can shorten the atrial effective refractory period and increase the induction of atrial fibrillation. lncRNA- 056298 promoted cardiac intrinsic autonomic nerve remodelling via endogenous competition with cfa-miR-185 to induce transcription of its target gene GAP43, thereby affecting the induction of atrial fibrillation. CONCLUSIONS: lncRNA-056298 regulates GAP43 by sponging miR-185, which affects cardiac intrinsic autonomic nerve remodelling and mediates atrial fibrillation induction after ganglionated plexus ablation.

Efficacy and safety of olmesartan medoxomil­amlodipine besylate tablets (Sevikar®) in older patients with essential hypertension: Subgroup analysis from the Sevikar study.

Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar®) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.

Efficacy and safety of olmesartan medoxomil-amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single-arm, multi-center, real-world study.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

Bromoform exposure is associated with non-melanoma skin cancer: evidence from NHANES 2011-2020.

Background: Non-melanoma skin cancer (NMSC) is a prevalent skin malignancy. It has been indicated in many studies that trihalomethanes (THMs) exposure has a strong association with tumors but has not been associated with NMSC. Our investigation aims to explore the association between THMs exposure and NMSC. Methods: Cross-sectional data from the 2011 to 2020 National Health and Nutrition Examination Survey (NHANES) was collected. Poisson regression and subgroup analyses were performed to evaluate the association between individual THMs components and NMSC. Fitted smoothing curves and generalized additive models were also used. Results: This study involved 5,715 individuals, 98 (1.7%) of whom self-reported NMSC. After adjusting for covariates, Poisson regression showed that higher blood TBM levels were associated with an increased likelihood of NMSC (OR = 1.03; 95% CI: 1.01-1.05, p = 0.002). However, the correlation between the blood levels of TCM, DBCM, and BDCM and the likelihood of NMSC was not statistically significant (all p > 0.05). Subgroup analysis and interaction tests showed no significant differences between blood TBM concentration and the likelihood of NMSC, indicating that age, gender, and race were significantly independent of this positive association (all p < 0.05). Conclusions: Our results implied that among adults older than 65 years old in the U.S., elevated blood TBM concentrations were positively associated with NMSC. More prospective investigations are required to validate this relationship with the early prevention of NMSC.

High-fat stimulation induces atrial neural remodeling by reducing NO production via the CRIF1/eNOS/P21 axi.

BACKGROUND: Autonomic remodeling of the atria plays a pivotal role in the development of atrial fibrillation (AF) and exerts a substantial influence on the progression of this condition. Hyperlipidemia is a predisposing factor for AF, but its effect on atrial nerve remodeling is unclear. The primary goal of this study was to explore the possible mechanisms through which the consumption of a high-fat diet (HFD) induces remodeling of atrial nerves, and to identify novel targets for clinical intervention. METHODS: Cell models were created in vitro by subjecting cells to palmitic acid (PA), while rat models were established by feeding them a high-fat diet. To investigate the interplay between cardiomyocytes and nerve cells in a co-culture system, we utilized Transwell cell culture plates featuring a pore size of 0.4 µm. The CCK-8 assay was employed to determine cell viability, fluorescent probe DCFH-DA and flow cytometry were utilized for measuring ROS levels, JC-1 was used to assess the mitochondrial membrane potential, the Griess method was employed to measure the nitric oxide (NO) level in the supernatant, a fluorescence-based method was used to measure ATP levels, and MitoTracker was utilized for assessing mitochondrial morphology. The expression of pertinent proteins was evaluated using western blotting (WB) and immunohistochemistry techniques. SNAP was used to treat nerve cells in order to replicate a high-NO atmosphere, and the level of nitroso was assessed using the iodoTMT reagent labeling method. RESULTS: The study found that cardiomyocytes' mitochondrial morphology and function were impaired under high-fat stimulation, affecting nitric oxide (NO) production through the CRIF1/SIRT1/eNOS axis. In a coculture model, overexpression of eNOS in cardiomyocytes increased NO expression. Moreover, the increased Keap1 nitrosylation within neuronal cells facilitated the entry of Nrf2 into the nucleus, resulting in an augmentation of P21 transcription and a suppression of proliferation. Atrial neural remodeling occurred in the HFD rat model and was ameliorated by increasing myocardial tissue eNOS protein expression with trimetazidine (TMZ). CONCLUSIONS: Neural remodeling is triggered by high-fat stimulation, which decreases the production of NO through the CRIF1/eNOS/P21 axis. Additionally, TMZ prevents neural remodeling and reduces the occurrence of AF by enhancing eNOS expression.

Atrial standstill associated with lamin A/C mutation: A case report.

The case report shares evidence for a better understanding of atrial standstill. This being a rare arrhythmogenic condition. This is a 46-year-old woman presented with multiple sites of arterial embolism, including lower extremity arteries, coronary artery, and cerebral artery. Unexpectedly, multiple arterial embolization in the patient was due to atrial standstill by transthoracic echocardiography and cardiac electrophysiological study. An additional family investigation revealed that the patient's brother and sister also suffered from this disease. In search of further understanding the case, we carried out the genetic testing of the family and a frame shift double-G insertion mutation at c.1567 in the LMNA gene was found in all the three individuals. The patient recovered well after anticoagulation therapy and left bundle branch area pacing. This report remarks on the importance of multiple sites of arterial embolism which should be wary of family atrial standstill.

Corrigendum: Retrospective analysis of longitudinal melanonychia: a Chinese experience.

[This corrects the article DOI: 10.3389/fped.2022.1065758.].

Divergent control and variation in bacterial and fungal necromass carbon respond to the abandonment of rice terraces.

The abandonment of rice terraces in hilly agroecosystems in recent decades has caused substantial changes in microbial characteristics and their impact on microbial necromass carbon (MNC) and soil organic carbon (SOC). Nevertheless, the regulatory mechanisms and impact pathways of MNC remain unclear. Here, soil samples were collected from 0 to 120 cm soil profiles in rice terraces, dry land (DL), and forest land (FL) for analysis. After converting rice terraces to DL and FL, MNC decreased significantly by 31.12% and 38.33%, while SOC decreased significantly by 51.26% and 29.87% respectively. These reductions are due to the loss of terrace management practices and associated functions. There were no significant changes in bacterial necromass carbon (BNC), whereas fungal necromass carbon (FNC) experienced a significant decrease. As a result, the decline in SOC may be primarily attributed to the reduction in FNC. BNC and FNC were regulated by bacterial life history strategies and fungal biomass, respectively. However, bacterial copiotrophs experienced a significant reduction after rice terrace abandonment. The regulation of BNC may be influenced by other factors, potentially offsetting the negative impact of abandonment. Dissolved organic carbon and bulk density were the primary control factors for bacterial community composition and fungal biomass, respectively. Additionally, the impact of soil layers on the alterations in MNC and SOC was more significant compared to the abandonment of rice terraces. These findings indicate that short-term abandonment of rice terraces results in a decrease in SOC, potentially compromising the ecological service function of the hilly agroecosystems. In the face of rapid population growth and global warming, it is crucial to minimize terrace abandonment and enhance utilization rates. This approach will effectively support sustainable terrace management and ecological services.

Serum uric acid: creatinine ratio (UCR) is associated with recurrence of atrial fibrillation after catheter ablation.

Background and aims: Studies showed that elevated preoperative serum uric acid(SUA) levels are associated with recurrence of atrial fibrillation(AF) after catheter ablation. UA:creatinine ratio(UCR - UA normalised for renal function) has appeared as a new biomarker and is considered to reflect endogenous UA levels preferably because it eliminates the influence of renal function. This study aimed to investigate the correlation between UCR and recurrence of AF after catheter ablation. Methods and results: A total of 233 consecutive patients with symptomatic, drug-refractory AF underwent catheter ablation. All participants underwent history-taking, physical examination and blood biochemistry analysis at baseline. After a mean follow-up of 23.99 ± 0.76 months, recurrence ratios for each UCR quartile (from lowest quartile to highest) were 10.9%, 23.6%, 23.6%, and 41.8%, respectively (P = 0.005). Multivariate Cox regression analysis revealed that UCR was an independent predictor of AF recurrence (HR 1.217, 95%CI 1.008-1.468; P = 0.041). Subgroup analysis showed that UCR was associated with AF recurrence in paroxysmal AF (HR 1.426, 95% CI 1.092-1.8608; P = 0.009) and in male patients (HR 1.407, 95% CI 1.015-1.950; P = 0.04). A cut-off point of 4.475 for the UCR had sensitivity of 65.5% and specificity of 59.6% in predicting AF recurrence (P = 0.001). Conclusion: Our results demonstrate that elevated preoperative UCR is associated with recurrence of AF after catheter ablation, and it indicate UCR maybe a predictive factor for the recurrence of AF.

Puerarin-Tanshinone IIA Suppresses atherosclerosis inflammatory plaque via targeting succinate/HIF-1α/IL-1ß axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory injury is an important pathological factor for the formation of atherosclerotic plaque. It is well known that Puerarin and Tanshinone IIA (Pue-Tan) can significantly reduce interleukin-1ß (IL-1ß) levels and delay the atherosclerosis (AS) process clinically in China. Previous evidence has shown that the Succinate/HIF-1α/IL-1ß inflammatory signaling axis (Succinate axis) promotes the progression of atherosclerotic inflammatory plaques. It is not clear whether Pue-Tan inhibits inflammatory plaques by reducing the level of IL-1ß through the succinate signaling axis. AIM OF STUDY: Find out the interaction between Pue-Tan targets and the succinate axis by means of network pharmacology and bioinformatics analysis and to further confirm whether Pue-Tan can inhibit vascular inflammation and delay the formation of atherosclerotic inflammatory plaques by targeting the succinate signaling axis. MATERIALS AND METHODS: Firstly, animal experiments were conducted to verify the changing relationship between Succinate and IL-1ß under Pue-Tan intervention. Secondly, network pharmacology approach was employed to uncover the specific targets of Pue-Tan in the intervention of AS from multiple levels of components, proteins, and pathways, and at the same time, the target must be a key factor of the succinate signaling axis. Autodock vina1.5.6 was applied to molecular docking for Pue-Tan and target protein. Subsequently, cells experiment and animal experiment were performed to verify Pue-Tan inhibiting the inflammatory progression of atherosclerosis by targeting succinate signaling axis. RESULTS: Firstly, we first found that the reduction of IL-1ß was positively correlated with succinate in the serum of Pue-Tan-treated mice. Secondly, network pharmacology compared with molecular docking showed that hypoxia-induced factor-1α (HIF-1α) was the key target of Pue-Tan and the key node of succinate singling axis. Finally, in vitro study, Pue-Tan significantly reduced the factors of succinate axis just as HIF-1α siRNA; in vivo study, we confirmed a decreased expression of succinate axis and ICAM-1 in the aorta of ApoE-/- mice under Pue-Tan intervention, which was consistent with the in vitro results. CONCLUSION: This study confirmed that Pue-Tan blocked the succinate axis by targeting HIF-1α to prevent the formation of atherosclerotic inflammatory plaques and delay the pathological process of AS. Network Pharmacology, Bioinformatics of Molecular Docking, and Molecular Biology Validation can be used as a effective way to discover and verify the pharmacological mechanism of TCM.

Mechanism of myocardial fibrosis regulation by IGF-1R in atrial fibrillation through the PI3K/Akt/FoxO3a pathway.

Atrial structural remodeling takes on a critical significance to the occurrence and maintenance of atrial fibrillation (AF). As revealed by recent data, insulin-like growth factor-1 receptor (IGF-1R) plays a certain role in tissue fibrosis. In this study, the mechanism of IGF-1R in atrial structural remodeling was examined based on in vivo and in vitro experiments. First, cluster analysis of AF hub genes was conducted, and then the molecular mechanism was proposed by which IGF-1R regulates myocardial fibrosis via the PI3K/Akt/FoxO3a pathway. Subsequently, the mentioned mechanism was verified in human cardiac fibroblasts (HCFs) and rats transduced with IGF-1 overexpression type 9 adeno-associated viruses. The results indicated that IGF-1R activation up-regulated collagen Ⅰ protein expression and Akt phosphorylation in HCFs and rat atrium. The administration of LY294002 reversed the above phenomenon, improved the shortening of atrial effective refractory period, and reduced the increased incidence of AF and atrial fibrosis in rats. The transfection of FoxO3a siRNA reduced the anti-fibrotic effect of LY294002 in HCFs. The above data revealed that activation of IGF-1R takes on a vital significance to atrial structural remodeling by facilitating myocardial fibrosis and expediting the occurrence and maintenance of AF through the regulation of the PI3K/Akt/FoxO3a signaling pathway.

The Diagnostic and Prognostic Value of Cardiac Magnetic Resonance Strain Analysis in Heart Failure with Preserved Ejection Fraction.

Background: Strain analysis of cardiac magnetic resonance (CMR) is critical for the diagnosis and prognosis of heart failure (HF) with preserved ejection fraction (HFpEF). Our study aimed to identify the diagnostic and prognostic value of strain analysis revealed by CMR in HFpEF. Methods: Participants in HFpEF and control were recruited according to the guideline. Baseline information, clinical parameters, blood samples were collected, and echocardiography and CMR examination were performed. Various parameters, including global longitudinal strain, global circumferential strain (GCS) and global radial strain in left ventricle (LV), right ventricle (RV), and left atrium, were measured from CMR. Receiver operator curve (ROC) was established to evaluate the diagnostic and prognostic value of strains in HFpEF. Results: Seven strains, with the exception of RVGCS, were employed to generate ROC curves after t-test. All strains had significant diagnostic value for HFpEF. The area under curve (AUC) of LV strains was greater than 0.7 and the AUC of the combined analysis of LV strains was 0.858 (95% confidence interval (CI): 0.798-0.919, sensitivity: 0.713, specificity: 0.875, P < 0.001), indicating that they had a higher diagnostic value than individual LV strains. However, individual strains had no predictive value in identifying end-point events in HFpEF, the AUC of coanalysis of LV strains was 0.722 (95% CI: 0.573-0.872, sensitivity: 0.500, specificity: 0.959, P = 0.004), indicating its prognostic relevance. Conclusion: Individual strain analysis in CMR may be useful for diagnosing HFpEF, the combination of LV strain analysis had the highest diagnostic value. Moreover, the prognostic value of individual strain analysis in predicting HFpEF outcome was not satisfactory while the combined usage of LV strain analysis was prognostically valuable in HFpEF outcome prediction.

Intermedin 1-53 Ameliorates Atrial Fibrosis and Reduces Inducibility of Atrial Fibrillation via TGF-ß1/pSmad3 and Nox4 Pathway in a Rat Model of Heart Failure.

OBJECTIVE: New drugs to block the occurrence of atrial fibrillation (AF) based on atrial structural remodeling (ASR) are urgently needed. The purpose of this study was to study the role of intermedin 1-53 (IMD1-53) in ASR and AF formation in rats after myocardial infarction (MI). MATERIAL AND METHODS: Heart failure was induced by MI in rats. Fourteen days after MI surgery, rats with heart failure were randomized into control (untreated MI group, n = 10) and IMD-treated (n = 10) groups. The MI group and sham group received saline injections. The rats in the IMD group received IMD1-53, 10 nmol/kg/day intraperitoneally for 4 weeks. The AF inducibility and atrial effective refractory period (AERP) were assessed with an electrophysiology test. Additionally, the left-atrial diameter was determined, and heart function and hemodynamic tests were performed. We detected the area changes of myocardial fibrosis in the left atrium using Masson staining. To detect the protein expression and mRNA expression of transforming growth factor-ß1 (TGF-ß1), α-SMA, collagen Ⅰ, collagen III, and NADPH oxidase (Nox4) in the myocardial fibroblasts and left atrium, we used the Western blot method and real-time quantitative polymerase chain reaction (PCR) assays. RESULTS: Compared with the MI group, IMD1-53 treatment decreased the left-atrial diameter and improved cardiac function, while it also improved the left-ventricle end-diastolic pressure (LVEDP). IMD1-53 treatment attenuated AERP prolongation and reduced atrial fibrillation inducibility in the IMD group. In vivo, IMD1-53 reduced the left-atrial fibrosis content in the heart after MI surgery and inhibited the mRNA and protein expression of collagen type Ⅰ and III. IMD1-53 also inhibited the expression of TGF-ß1, α-SMA, and Nox4 both in mRNA and protein. In vivo, we found that IMD1-53 inhibited the phosphorylation of Smad3. In vitro, we found that the downregulated expression of Nox4 was partly dependent on the TGF-ß1/ALK5 pathway. CONCLUSIONS: IMD1-53 decreased the duration and inducibility of AF and atrial fibrosis in the rats after MI operation. The possible mechanisms are related to the inhibition of TGF-ß1/Smad3-related fibrosis and TGF-ß1/Nox4 activity. Therefore, IMD1-53 may be a promising upstream treatment drug to prevent AF.

Renal Safety of Sacubitril/Valsartan: A Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: As a first-line therapy, sacubitril/valsartan (S/V) plays a significant role in the treatment of heart failure. However, its effect on renal function is still uncertain. We searched PubMed, EMBASE, the Cochrane Library, and Clinical Trials for randomized controlled trials to evaluate the effect of S/V on renal function in patients. The results are reported as the mean difference, relative ratio, and 95% confidence intervals. A total of 13 randomized controlled trials were included (19,367 patients). Among them, 11 studies focused on patients with heart failure, 1 on patients with acute myocardial infarction, and 1 on patients with chronic kidney disease. We found that fewer worsening renal function events, elevated creatine level events, and severe hyperkalemia events (blood potassium >6.0 mmol/L) occurred in the S/V group than those in the renin-angiotensin-aldosterone system inhibitor (RASi) group. The estimated glomerular filtration rate decreased in both the S/V group and the RASi group, but the change was more obvious in the RASi group. There was no significant difference in hyperkalemia events (blood potassium >5.5 mmol/L) between the 2 groups. Subgroup analysis showed that with the extension of follow-up time (>6 months), worsening renal function events occurred less frequently in the S/V group than in the RASi group. Existing evidence has shown that S/V is superior to RASi in general renal safety. Perhaps with the prolongation of treatment time, the advantages of S/V are more obvious.

Case report: Dual atrioventricular nodal non-reentrant tachycardia with six types of ECG patterns leading to tachycardia-induced cardiomyopathy in a 51-year-old man.

More than three types of ECG manifestations in one patient with dual atrioventricular nodal non-reentrant tachycardia (DAVNNT) are rare. We report a 51-year-old male patient with DAVNNT consisting of six types of ECG patterns leading to tachycardia-induced cardiomyopathy. After radiofrequency ablation of the slow pathway, DAVNNT was eliminated and cardiac function was restored.

Contemporary oral anticoagulant therapy of patients with atrial fibrillation in China: Status, obstacles, and strategies for improvement.

Atrial fibrillation (AF) and subsequent stroke and death have become major public health problems in China. Oral anticoagulant (OAC) forms the backbone of prevention of AF-related stroke. However, the quality of OAC use in AF patients in China is not clear. The focus of this narrative review is to summarize the current status of OAC therapy in China and compare it with the studies conducted internationally. In general, most data of OAC use in China were reported around 10-50%, with an increasing proportion of high-risk patients receiving OACs, however, still much lower than those in other countries and regions. Moreover, the phenomenon of inappropriate OAC prescribing and poor long-term persistence and adherence with OAC therapy in AF patients in China have also been noted. The 1-year adherence and persistence of OACs are as low as 50%. Multiple factors from the physicians, patients, and OAC drugs contribute to these phenomena. The management of OACs in AF patients in China needs to be further improved by the joint efforts of healthcare administration (policy makers) and health systems including medical associations, hospitals, and physicians.

The diagnostic value of peroxisome proliferator-activated receptor-γ coactivator-1α in identifying different chronic heart failure phenotypes.

Background: Despite advances in diagnosing and treating chronic heart failure (HF), the underlying mechanisms in different HF phenotypes remain unclear. Mitochondrial energy metabolism is crucial in HF etiology. Our study aimed to explore the value of metabolic-associated biomarker peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in identifying different HF phenotypes. Methods: A total of 172 participants were enrolled in the Affiliated Hospital of Xuzhou Medical University and were subsequently divided into four groups based on the European Society of Cardiology HF management guideline: the non-HF control (Control, N = 46), heart failure with reduced ejection fraction (HFrEF, N = 54), heart failure with mildly reduced ejection fraction (HFmrEF, N = 22), and heart failure with preserved ejection fraction (HFpEF, N = 50) groups. Each participant's baseline data were recorded, blood samples were taken, and echocardiography was conducted. The level of PGC1α expression was determined using an enzyme-linked immunosorbent assay (ELISA) kit. The receiver operative characteristics (ROC) curve was further established in the four groups to assess the diagnostic value for overall HF and each HF phenotype with the calculation of the area under the curve (AUC) and 95% confidence interval (CI). Results: PGC1α expression was significantly increased in HF patients (315.0 ± 69.58 nmol/L) compared to non-HF participants (233.3 ± 32.69 nmol/L). Considering different HF phenotypes, PGC1α expression was considerably higher in the HFmrEF group (401.6 ± 45.1 nmol/L)than in the other two phenotypes (299.5 ± 62.27 nmol/L for HFrEF and 293.5 ± 56.37 nmol/L for HFpEF, respectively).Furthermore, the AUCs of PGC1α in overall HF and each HF phenotype were all over 0.8, showing the ideal diagnostic value. Additionally, we provided the cut-off criteria for clinical use, which needs further validation. There was no significant correlation between PGC1α and N-terminal (NT)-prohormone B-type natriuretic peptide (BNP)/blood glucose, suggesting that PGC1α might exert a unique function in HF yet in a different pattern. Conclusion: We discovered that PGC1α could be used as a potential biomarker for differentiating HF patients from those without HF and for distinguishing HFmrEF from HFrEF and HFpEF.

Differential Proteomic Profiles of Coronary Serum Exosomes in Acute Myocardial Infarction Patients with or Without Diabetes Mellitus: ANGPTL6 Accelerates Regeneration of Endothelial Cells Treated with Rapamycin via MAPK Pathways.

PURPOSE: Delayed re-endothelialization after coronary drug-eluting stent implantation is associated with an increased incidence of late in-stent thrombosis. Serum exosomes exhibit controversial effects on promoting endothelialization. This study aimed to compare the angiogenic effects of serum exosomes derived from patients with acute myocardial infarction (AMI) and AMI plus diabetes mellitus (DM) and to explore the underlying mechanisms. METHODS: Serum exosomes derived from patients in the control (Con-Exos), AMI (AMI-Exos), and AMI plus DM (AMI+DM-Exos) groups were isolated and identified using standard assays. CCK-8, wound healing, and tube formation assays were performed to detect the angiogenic abilities of serum exosomes on rapamycin-conditioned human umbilical vein endothelial cells (HUVECs). Differential proteomic profiles between AMI-Exos and AMI+DM-Exos were analyzed by mass spectrometry. The effects and potential mechanisms of exosomal angiopoietin-like 6 (ANGPTL6) were investigated. RESULTS: Functional assays indicated that compared with Con-Exos, AMI-Exos enhanced, whereas AMI+DM-Exos inhibited the cell proliferation, migration, and tube formation of rapamycin-conditioned HUVECs. Subsequently, 28 differentially expressed proteins between AMI-Exos and AMI+DM-Exos were identified, which were correlated with material transportation, immunity, and inflammatory reaction. Moreover, ANGPTL6 was highly enriched in AMI-Exos. Overexpression and knockdown of ANGPTL6 enhanced and inhibited angiogenesis, respectively. Furthermore, the effect of ANGPTL6 on angiogenesis was mediated via the activation of ERK 1/2, JNK, and p38 pathways. The inhibition of ERK 1/2 signaling markedly attenuated the migration abilities of overexpressing ANGPTL6. CONCLUSION: Diabetes impairs the regenerative capacities of serum exosomes. Exosomal ANGPTL6 contributes to endothelial repair and is a novel therapeutic target for enhanced stent endothelization.