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OBJECTIVES: To investigate the mechanism of electroacupuncture (EA) at "Neiguan" (PC6) in impro-ving myocardial electrical remodeling in rats with acute myocardial infarction (AMI) by enhancing transient outward potassium current. METHODS: A total of 30 male SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The AMI model was established by subcutaneous injection with isoprenaline (ISO, 85 mg/kg). EA was applied to left PC6 for 20 min, once daily for 5 days. Electrocardiogram (ECG) was recorded after treatment. TTC staining was used to observe myocardial necrosis. HE staining was used to observe the pathological morphology of myocardial tissue and measure the cross-sectional area of myocardium. Potassium ion-related genes in myocardial tissue were detected by RNA sequencing. The mRNA and protein expressions of Kchip2 and Kv4.2 in myocardial tissue were detected by real-time fluorescence quantitative PCR and Western blot, respectively. RESULTS: Compared with the control group, cardiomyocyte cross-sectional area in the model group was significantly increased (P<0.01), the ST segment was significantly elevated (P<0.01), and QT, QTc, QTd and QTcd were all significantly increased (P<0.05, P<0.01). After EA treatment, cardiomyocyte cross-sectional area was significantly decreased (P<0.01), the ST segment was significantly reduced (P<0.01), and the QT, QTc, QTcd and QTd were significantly decreased (P<0.01, P<0.05). RNA sequencing results showed that a total of 20 potassium ion-related genes co-expressed by the 3 groups were identified. Among them, Kchip2 expression was up-regulated most notablely in the EA group. Compared with the control group, the mRNA and protein expressions of Kchip2 and Kv4.2 in the myocardial tissue of the model group were significantly decreased (P<0.01, P<0.05), while those were increased in the EA group (P<0.01, P<0.05). CONCLUSIONS: EA may improve myocardial electrical remodeling in rats with myocardial infarction, which may be related to its functions in up-regulating the expressions of Kchip2 and Kv4.2.

Core outcome sets for myocardial infarction in clinical trials of traditional Chinese medicine and Western medicine.

BACKGROUND: Clinical trials of traditional Chinese medicine (TCM) and Western medicine showed there was heterogeneity of outcome reporting in myocardial infarction (MI). Developing a core outcome set (COS) might improve the consistency of outcome reporting in future clinical trials. METHODS: A list of outcomes was developed based on a systematic review of randomized controlled trials (RCTs) of MI and semistructured interviews with MI patients. Two rounds of Delphi survey for clinicians, researchers, journal editors, and methodologists were conducted. An online questionnaire sent to nurses. After an online consensus meeting, a COS for MI RCTs was developed. RESULTS: After extracted data from clinical trials and discussed, 216 outcomes were included in round 1 of the Delphi survey. Seventy-four participants completed round 1 of the Delphi survey. Sixty-five participants completed round 2 of the Delphi survey. Twenty-two nurses completed the online questionnaire. Fifteen participants attended the online consensus meeting, and 14 of them voted and determined the final COS. For all types of MI, it was recommended that left ventricular ejection fraction and quality of life be measured and reported. For acute MI, the participants in the consensus meeting recommended the following core outcomes: death from cardio-cerebrovascular disease, cardiogenic shock, heart failure, troponin I, troponin T, creatine kinase isoenzyme, Killip class, target vessel revascularization, and emergency CABG. For previous MI, recurrent MI, recurrent angina pectoris, and heart failure readmission were recommended. CONCLUSIONS: The COS for MI in RCTs provides recommendations for clinical trials that seek to improve outcomes for patients with MI.

Application Effect Evaluation of Optimizing Emergency Nursing Process Before Emergency Coronary Intervention in Patients with AMI and Hypertension.

Objective: The study aimed to assess the impact of optimizing the emergency nursing process on certain outcomes in AMI patients with hypertension undergoing coronary intervention therapy. Methods: This is a retrospective cohort study, a total of 90 patients with AMI complicated with hypertension admitted from October 2020 to March 2022 to observe the effect and safety of two different nursing methods in patients with AMI complicated with hypertension. According to the different nursing process, the subjects were divided into the optimization and conventional groups, with 45 cases in each group. Then, the rescue efficiency, success rate, recurrence rate, re-PCI rate, negative emotions, and adverse reactions of the two groups were observed. Results: The results showed that the first aid time (39.23±6.28 vs 49.78±9.14), PCI time (45.13±8.60 vs 60.40±8.16) and ECG time (4.18±0.69 vs 6.87±1.00), success rate (93.33% vs 66.67%) and recurrence rate (8.89% vs 22.22%) of the study subjects undergoing the optimized emergency nursing process were significantly better than those undergoing the general emergency nursing process (P < .05), and their negative emotions (7.51±1.77 vs 14.07±1.93) and adverse reactions (3 vs 9) were significantly lower than those of the conventional group (P < .05). Conclusions: It is suggested that optimizing the emergency nursing process before PCI for patients with AMI complicated with hypertension positively impacts the clinical efficacy and prognosis. Optimizing the emergency nursing process may potential benefits for patient health, healthcare resource utilization, or the quality of care, which should be consider in clinical practice.

An injectable carrier for spatiotemporal and sequential release of therapeutic substances to treat myocardial infarction.

Myocardial infarction (MI) has become the primary cause of cardiovascular mortality, while the current treatment methods in clinical all have their shortcomings. Injectable biomaterials have emerged as a promising solution for cardiac tissue repair after MI. In this study, we designed a smart multifunctional carrier that could meet the treatment needs of different MI pathological processes by programmatically releasing different therapeutic substances. The carrier could respond to inflammatory microenvironment in the early stage of MI with rapid release of curcumin (Cur), and then sustained release recombinant humanized collagen type III (rhCol III) to treat MI. The rapid release of Cur reduced inflammation and apoptosis in the early stages, while the sustained release of rhCol III promoted angiogenesis and cardiac repair in the later stages. In vitro and in vivo results suggested that the multifunctional carrier could effectively improve cardiac function, promote the repair of infarcted tissue, and inhibit ventricular remodeling by reducing cell apoptosis and inflammation, and promoting angiogenesis in the different pathological processes of MI. Therefore, this programmed-release carrier provides a promising protocol for MI therapy.

Cardiomyocyte precursors generated by direct reprogramming and molecular beacon selection attenuate ventricular remodeling after experimental myocardial infarction.

BACKGROUND: Direct cardiac reprogramming is currently being investigated for the generation of cells with a true cardiomyocyte (CM) phenotype. Based on the original approach of cardiac transcription factor-induced reprogramming of fibroblasts into CM-like cells, various modifications of that strategy have been developed. However, they uniformly suffer from poor reprogramming efficacy and a lack of translational tools for target cell expansion and purification. Therefore, our group has developed a unique approach to generate proliferative cells with a pre-CM phenotype that can be expanded in vitro to yield substantial cell doses. METHODS: Cardiac fibroblasts were reprogrammed toward CM fate using lentiviral transduction of cardiac transcriptions factors (GATA4, MEF2C, TBX5, and MYOCD). The resulting cellular phenotype was analyzed by RNA sequencing and immunocytology. Live target cells were purified based on intracellular CM marker expression using molecular beacon technology and fluorescence-activated cell sorting. CM commitment was assessed using 5-azacytidine-based differentiation assays and the therapeutic effect was evaluated in a mouse model of acute myocardial infarction using echocardiography and histology. The cellular secretome was analyzed using mass spectrometry. RESULTS: We found that proliferative CM precursor-like cells were part of the phenotype spectrum arising during direct reprogramming of fibroblasts toward CMs. These induced CM precursors (iCMPs) expressed CPC- and CM-specific proteins and were selectable via hairpin-shaped oligonucleotide hybridization probes targeting Myh6/7-mRNA-expressing cells. After purification, iCMPs were capable of extensive expansion, with preserved phenotype when under ascorbic acid supplementation, and gave rise to CM-like cells with organized sarcomeres in differentiation assays. When transplanted into infarcted mouse hearts, iCMPs prevented CM loss, attenuated fibrotic scarring, and preserved ventricular function, which can in part be attributed to their substantial secretion of factors with documented beneficial effect on cardiac repair. CONCLUSIONS: Fibroblast reprogramming combined with molecular beacon-based cell selection yields an iCMP-like cell population with cardioprotective potential. Further studies are needed to elucidate mechanism-of-action and translational potential.

Efficacy and safety of non-pharmacological therapy under the guidance of TCM theory in the treatment of anxiety in patients with myocardial infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: With the increasing pressures of modern life and work, combined with a growing older population, the incidence of comorbid anxiety and myocardial infarction (MI) is increasing. Anxiety increases the risk of adverse cardiovascular events in patients with MI and significantly affects their quality of life. However, there is an ongoing controversy regarding the pharmacological treatment of anxiety in patients with MI. The concomitant use of commonly prescribed selective serotonin reuptake inhibitors (SSRIs) and antiplatelet medications such as aspirin and clopidogrel may increase the risk of bleeding. Conventional exercise-based rehabilitation therapies have shown limited success in alleviating anxiety symptoms. Fortunately, non-pharmacological therapies based on traditional Chinese medicine (TCM) theory, such as acupuncture, massage, and qigong, have demonstrated promising efficacy in treating MI and comorbid anxiety. These therapies have been widely used in community and tertiary hospital settings in China to provide new treatment options for patients with anxiety and MI. However, current studies on non-pharmacological TCM-based therapies have predominantly featured small sample sizes. This study aims to comprehensively analyze and explore the effectiveness and safety of these therapies in treating anxiety in patients with MI. METHOD: We will systematically search six English and four Chinese databases by employing a pre-defined search strategy and adhering to the unique rules and regulations of each database to identify studies that fulfilled our inclusion criteria, to qualify for inclusion, patients must be diagnosed with both MI and anxiety, and they must have undergone non-pharmacological TCM therapies, such as acupuncture, massage, or qigong, whereas the control group received standard treatments. The primary outcome measure will be alterations in anxiety scores, as assessed using anxiety scales, with secondary outcomes encompassing the evaluations of cardiopulmonary function and quality of life. We will utilize RevMan 5.3 to conduct a meta-analysis of the collected data, and subgroup analyses will be executed based on distinct types of non-pharmacological TCM therapies and outcome measures. RESULTS: A narrative summary and quantitative analysis of the existing evidence on the treatment of anxiety patients with MI using non-pharmacological therapies guided by Traditional Chinese Medicine theory. CONCLUSION: This systematic review will investigate whether non-pharmacological interventions guided by TCM theory are effective and safe for anxiety in patients with MI, and provide evidence-based support for their clinical application. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022378391.

Electroacupuncture improves cardiac function after myocardial infarction by regulating the mobilization and migration of endogenous stem cells.

OBJECTIVE: The aim of this study was to explore the role and mechanisms of electroacupuncture (EA) in the regulation of chemokines in endogenous stem cell mobilization and myocardial regeneration after myocardial infarction (MI). METHODS: An MI model was constructed in adult male Sprague-Dawley rats by ligating the left anterior descending coronary artery. After 4 weeks of treatment, echocardiography was used to detect changes in cardiac function, and Masson's trichrome staining was used to detect collagen deposition. In addition, immunofluorescence staining was applied to examine von Willebrand factor (vWF)-positive vessels, the expression of cardiac troponin T (cTnT) and proliferation marker Ki67, and the number of c-kit-positive, C-X-C chemokine receptor type 4 (CXCR4)-positive, and Sca-1-positive endogenous stem cells in the infarcted area. In addition, the expression of stromal cell-derived factor (SDF)-1 and stem cell factor (SCF) was detected. RESULTS: EA increased the ejection fraction after MI, reduced collagen deposition and cellular apoptosis, and increased the number of blood vessels compared with an untreated model group. EA significantly promoted cellular proliferation, except for myocardial cells, and significantly increased the number of c-kit-, CXCR4- and Sca-1-positive stem cells. Moreover, the expression of SDF-1 and SCF in myocardial tissue in the EA group was significantly higher than that in the (untreated) MI group. CONCLUSIONS: EA appears to promote angiogenesis and reduce collagen deposition, thus improving the cardiac function of rats with MI. The underlying mechanism of action may involve endogenous stem cell mobilization mediated by SDF-1/CXCR4 and SCF/c-kit.

Effect of mindfulness-based stress reduction in patients with acute myocardial infarction after successful primary percutaneous coronary intervention: a retrospective study.

OBJECTIVE: This study aimed to examine the effects of mindfulness-based stress reduction (MBSR) in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PPCI). METHODS: A retrospective study was conducted with data collected from AMI patients who underwent successful PPCI. The study included 61 cases that received 8-week MBSR intervention (MBSR group) and 61 cases that received weekly health education (control group) over the same period. Outcome measures, including hemodynamic parameters, psychosocial characteristics [Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), Perceived Social Support Scale (PSSS)], health-related quality of life [HRQoL, 7-item Seattle Angina Questionnaire (SAQ-7)], and major adverse cardiovascular events (MACE), were assessed at baseline (T1), post-intervention (T2), 1 month after the post-intervention (T3) and 3 months after the post-intervention (T4). RESULTS: Compared to the control group, the MBSR group showed improvements in blood pressure, specifically in systolic blood pressure (SBP) at T4, and diastolic blood pressure (DBP) at T3 and T4, and mean arterial blood pressure (MABP) at T3 and T4. Additionally, the MBSR group had lower scores of anxiety and perceived stress (HADS, PSS) and higher scores of perceived social support (PSSS) after the intervention. Furthermore, the MBSR group had higher scores on the SAQ-7 at all measurement points. The control group had a significantly higher total MACE rate compared to the MBSR group (26.23% vs. 9.84%). CONCLUSIONS: This study provides support for the potential benefits of MBSR as an adjunctive treatment for AMI patients undergoing PPCI.

Characteristics of Onset Seasons Within One Year and Time Periods Within One Day of Acute Myocardial Infarction.

Context: Some studies have found that the onset of acute myocardial infarctions (AMIs) exhibits regular daily and seasonal changes. However, researchers have provided no authoritative explanations about the mechanisms to assist in clinical practice. Objective: The study intended to examine the characteristics of the onset seasons within in one year and time periods within one day of an AMI, determine the correlation between morbidity rates from AMIs at different time points, and analyze the dendritic cell (DC) functions, thus providing a reference for clinical prevention and treatment. Design: The research team a retrospective analysis of clinical data of AMI patients. Setting: The study took place at the Affiliated Hospital of Weifang Medical University in Weifang, China. Participants: Participants were 339 AMI patients whom the hospital had admitted and treated. The research team divided participants into two groups: (1) those ≥ 60 years old and (2) those <60 years old. Outcome Measures: The research team: (1) calculated and recorded the onset times and percentages for all participants at the different time points and determined the morbidity or death rates for the periods, (2) analyzed the seasonal distribution for the two groups using the circular-distribution method, (3) measured the DC functions of all participants, (4) analyzed the DC functions, and (5) determined the correlation between the morbidity and death rates from AMIs at different time points. Results: The morbidity rate for all participants from AMIs during the period from 6:01 am to 12:00 PM was significantly higher than that between 0:01 AM and 6:00 AM (P < .001), between 12.01 PM and 18:00 PM (P < .001), and between 18:00 pm and 24:00 PM (P < .001). The death rate for all participants from AMIs between January and March was significantly higher than that between April and June (P = .022) and that between July to September (P = .044). The morbidity rate from AMIs in different time periods within one day and the death rate from AMIs in different seasons were positively correlated with both the expression level of cluster of differentiation 86 (CD86) on the DCs and the absorbance (A) value under the mixed lymphocyte reaction (MLR) condition (all P < .001). Conclusions: The time period between 6:01 AM and 12:00 PM within one day and the seasonal period between January and March within one year were the periods with high levels of morbidity and death, respectively, and the onset of AMIs had a correlation with DC functions. Medical practitioners should take specific preventive measures to reduce the morbidity and death rates from AMIs.

Phase I cardiac rehabilitation with 5-phase music after emergency percutaneous coronary intervention for acute myocardial infarction: A prospective randomized study.

BACKGROUND: Five-phase music therapy was reported to be effective in the treatment and rehabilitation of several diseases. This study explored the effect of phase I cardiac rehabilitation combined with 5-phase music in acute myocardial infarction (AMI) patients after emergency percutaneous coronary intervention. METHODS: This prospective pilot study enrolled AMI patients who received percutaneous coronary intervention from the Traditional Chinese Medicine Hospital from July 2018 to December 2019. The participants were randomized in a 1:1:1 ratio to the control, cardiac rehabilitation, and rehabilitation-music groups. The primary endpoint was the hospital anxiety and depression scale. The secondary endpoints were the myocardial infarction dimensional assessment scale, self-rating sleep status, 6-minute walk test, and left ventricular ejection fraction. RESULTS: The study included 150 AMI patients (n = 50/group). Hospital anxiety and depression scale showed significant time effects for both anxiety and depression (both P < .05), a treatment effect for depression (P = .02), and an interaction effect for anxiety (P = .02). A time effect was also observed for diet, sleep disorders, 6-minute walk test, and left ventricular ejection fraction (all P < .001). A difference among groups was observed for emotional reaction (P = .001). Interactions effects were observed for diet (P = .01) and sleep disorders (P = .03). CONCLUSION: Phase I cardiac rehabilitation combined with 5-phase music could alleviate anxiety and depression and improve sleep quality.

Comparative Study of Different Acupoints for Treating Acute Myocardial Ischemia in Mice.

Acupuncture point specificity has been recognized as a key scientific issue in traditional Chinese medicine (TCM), but there is limited clinical trial or animal study to verify the characteristics of PC6, BL15, and ST36 in the protection from myocardial injury. We aimed to compare the effects among these three acupoints on the acute myocardial infarction mice model and to explore possible mechanisms for the first time. We found that PC6 is the most appropriate acupoint to deliver efficacy and safety to treat acute MI in mice. BL15 stimulation improved the systolic function, but increased the risk of arrhythmia. ST36 only slightly attenuated systolic function and had no effect on arrhythmia during MI. RNA profiles of skin tissue in local acupoints demonstrated that the most altered DEGs and related pathways may partly support its best effects of PC6 treatment on MI injury, and support the observed phenomenon of the acupoint specificity.

Electroacupuncture Treats Myocardial Infarction by Influencing the Regulation of Substance P in the Neurovascular to Modulate PGI2/TXA2 Metabolic Homeostasis via PI3K/AKT Pathway: A Bioinformatics-Based Multiomics and Experimental Study.

Acute myocardial infarction (AMI) is the most severe form of coronary heart disease caused by ischemia and hypoxia. The study is aimed at investigating the role of neuropeptides and the mechanism of electroacupuncture (EA) in acute myocardial infarction (AMI) treatment. Compared with the normal population, a significant increase in substance P (SP) was observed in the serum of patients with AMI. PGI2 expression was increased in the SP-treated AMI mouse model, and TXA2 expression was decreased. And PI3K pathway-related genes, including Pik3ca, Akt, and Mtor, were upregulated in myocardial tissue of SP-treated AMI patients. Human cardiomyocyte cell lines (HCM) treated with SP increased mRNA and protein expression of PI3K pathway-related genes (Pik3ca, Pik3cb, Akt, and Mtor). Compared to MI control and EA-treated MI rat models, Myd88, MTOR, Akt1, Sp, and Irak1 were differentially expressed, consistent with in vivo and in vitro studies. EA treatment significantly enriched PI3K/AKT signaling pathway genes within MI-associated differentially expressed genes (DEGs) according to Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, it was confirmed by molecular docking analysis that PIK3CA, AKT1, and mTOR form stable dockings with neuropeptide SP. PI3K/AKT pathway activity may be affected directly or indirectly by EA via SP, which corrects the PGI2/TXA2 metabolic imbalance in AMI. MI treatment is now better understood as a result of this finding.

Cerebellar fastigial nucleus electrostimulation attenuates inflammation in a Post-Infarction rat model by activating cholinergic anti-inflammatory pathway.

There are negative correlations between indices of heart rate variability (HRV) and markers of inflammation. The inflammation plays an important role in myocardial damages after myocardial infarction (MI). Our previous study found that fastigial nucleus electrostimulation (FNS) improved abnormal HRV in a rat model of MI. Whether it can reduce inflammation and improve cardiac function after MI and the underlying mechanisms remain unknown. 66 Sprague Dawley rats were randomly divided into 4 groups as follows: i) Sham group (sham operation); ii) MI group (left anterior descending coronary artery ligation); iii) FNS + MI group (left fastigial nucleus electrostimulation plus MI); iv) FNL + FNS + MI group (left fastigial nucleus lesion plus FNS plus MI). The serum expressions of acetylcholine (ACh), pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and anti-inflammatory cytokines IL-10 were measured by ELISA. Subsequently, the infarct size, the infiltration of inflammatory cells, the fibrotic area, and cardiac function were also evaluated. Additionally, the expressions of the cholinergic anti-inflammatory pathway (CAP)-related proteins in infarct tissue, such as nuclear factor kappa B (NF-κB) and singal transducers and activators of transcription 3 (STAT3), were determined by Western blot. We found that FNS significantly increased ACh and IL-10 levels in serum, and decreased TNF-α and IL-6 levels. FNS significantly attenuated inflammatory cell infiltration, reduced infarct size, decreased fibrosis, increased left ventricular ejection fraction, and reduced mortality. Besides, the ratios of phosphorylated-STAT3/STAT3 and phosphorylated-NF-κB/NF-κB in infarct tissue significantly elevated after MI. FNS reduced the ratios of p-STAT3/STAT3 and p-NF-κB/NF-κB in infarct tissue. The protective effects of FNS were partially reversed by the fastigial nucleus lesion. Our data suggested that FNS can alleviate the inflammation after MI, and its cardiac neuroprotective mechanism may be achieved by increasing vagal tone, releasing ACh, and further activating the CAP via α7 nicotinic acetylcholine receptor. The precise mechanism remains to be elucidated.

Anxiety following myocardial infarction: A systematic review of psychological interventions.

OBJECTIVE: Anxiety is highly prevalent following myocardial infarction (MI) and is linked with adverse effects on a person's recovery, quality of life, physical health, and life expectancy. The primary objective of this systematic review was to assess the effectiveness of psychological interventions for anxiety following MI. METHOD: CINAHL, Medline, PsycINFO, PsycARTICLES, Cochrane Library, EMBASE, and Web of Science were systematically searched for studies that provided information on anxiety pre and post psychological intervention following MI. RESULTS: Eighteen studies were included (15 randomized controlled trials [RCTs] and three non-RCTs). Within these studies, psychological interventions comprised cognitive behavioral therapy, eye movement desensitization reprocessing, counseling, psychotherapy, psychological/psychosocial cardiac rehabilitation, illness perception interventions, relaxation training, mindfulness, stress management, and other psychological-based programmes. Ten studies reported a significant decrease in anxiety following a psychological intervention, when compared with usual care. Three studies noted mixed results, and five studies reported no significant difference in anxiety following a psychological intervention. The interventions varied in length, setting, facilitation, and format. Poor reporting of information increased the risk of bias within studies. CONCLUSION: Psychological interventions may be beneficial to individuals who experience anxiety following a MI. No particular type of psychological intervention appears to be superior to others within the existing literature. Further rigorous research is needed to identify the needs of this population and the specific form of psychological intervention that is most effective in alleviating anxiety following MI. Clinical implications and recommendations for future research are provided. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Tongxinluo-pretreated mesenchymal stem cells facilitate cardiac repair via exosomal transfer of miR-146a-5p targeting IRAK1/NF-κB p65 pathway.

BACKGROUND: Bone marrow cells (BMCs), especially mesenchymal stem cells (MSCs), have shown attractive application prospects in acute myocardial infarction (AMI). However, the weak efficacy becomes their main limitation in clinical translation. Based on the anti-inflammation and anti-apoptosis effects of a Chinese medicine-Tongxinluo (TXL), we aimed to explore the effects of TXL-pretreated MSCs (MSCsTXL) in enhancing cardiac repair and further investigated the underlying mechanism. METHODS: MSCsTXL or MSCs and the derived exosomes (MSCsTXL-exo or MSCs-exo) were collected and injected into the infarct zone of rat hearts. In vivo, the anti-apoptotic and anti-inflammation effects, and cardiac functional and histological recovery were evaluated. In vitro, the apoptosis was evaluated by western blotting and flow cytometry. miRNA sequencing was utilized to identify the significant differentially expressed miRNAs between MSCsTXL-exo and MSCs-exo, and the miRNA mimics and inhibitors were applied to explore the specific mechanism. RESULTS: Compared to MSCs, MSCsTXL enhanced cardiac repair with reduced cardiomyocytes apoptosis and inflammation at the early stage of AMI and significantly improved left ventricular ejection fraction (LVEF) with reduced infarct size in an exosome-dependent way. Similarly, MSCsTXL-exo exerted superior therapeutic effects in anti-apoptosis and anti-inflammation, as well as improving LVEF and reducing infarct size compared to MSCs-exo. Further exosomal miRNA analysis demonstrated that miR-146a-5p was the candidate effector of the superior effects of MSCsTXL-exo. Besides, miR-146a-5p targeted and decreased IRAK1, which inhibited the nuclear translocation of NF-κB p65 thus protecting H9C2 cells from hypoxia injury. CONCLUSIONS: This study suggested that MSCsTXL markedly facilitated cardiac repair via a new mechanism of the exosomal transfer of miR-146a-5p targeting IRAK1/NF-κB p65 pathway, which has great potential for clinical translation.

The e-mental health treatment in Stockholm myocardial infarction with non-obstructive coronaries or Takotsubo syndrome study (E-SMINC): a study protocol for a randomised controlled trial.

BACKGROUND: In the aftermath of a myocardial infarction with non-obstructive coronary arteries (MINOCA) or Takotsubo syndrome (TS), patients commonly express high levels of stress and anxiety. Current treatment alternatives rarely address these issues. METHODS: The study is a randomised controlled trial, where 90 patients with a discharge diagnosis of MINOCA or TS who also report symptoms of stress or anxiety will be randomised 2-6 weeks after their cardiac event. The treatment consists of 10 weeks of Internet-based cognitive behaviour therapy (CBT) and starts immediately after randomisation for the treatment group. The control group receives usual care. Main outcomes are symptoms of anxiety measured with the Hospital Anxiety and Depression scale, anxiety subscale, and perceived stress measured with the Perceived Stress Scale, 14-item version, 10 weeks after randomisation. Secondary measures include cardiac specific anxiety, symptoms of post-traumatic stress, quality of life, cortisol measured in hair and physiological stress responses (heart rate variability, blood pressure and saliva cortisol) during a stress procedure. Ten weeks after randomisation, the control group will also receive treatment. Long-term follow-up in the self-report measures mentioned above will be conducted 20 and 50 weeks after randomisation where the total group's development over time is followed, and the groups receiving intervention early versus late compared. DISCUSSION: At present, there are no randomised studies evaluating psychological treatment for patients with MINOCA or TS. There is an urgent need for treatment alternatives aiming at relieving stress and anxiety considering the high mental stress and anxiety levels observed in MINOCA and TS, leading to decreased quality of life. CBT aiming at reducing mental stress has been shown to be effective regarding prognosis in patients with coronary artery disease. The current protocol describes a randomised open-label controlled trial evaluating an Internet-based CBT program for reduction of stress and anxiety in patients with increased mental stress and/or anxiety with a discharge diagnosis of either MINOCA or TS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04178434 . Registered on 26 November 2019.

Cellular cross-talk in heart repair.

The cytokine meteorin-like (METRNL) improves cardiac function after heart attack in mice.