Enhancing miR-19a/b induced cardiomyocyte proliferation in infarcted hearts by alleviating oxidant stress and controlling miR-19 release.

Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that ∼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.

Effects of beta-blockers on quality of life and well-being in patients with myocardial infarction and preserved left ventricular function-a prespecified substudy from REDUCE-AMI.

AIMS: In the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) study, long-term beta-blocker use in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction demonstrated no effect on death or cardiovascular outcomes. The aim of this prespecified substudy was to investigate effects of beta-blockers on self-reported quality of life and well-being. METHODS AND RESULTS: From this parallel-group, open-label, registry-based randomized clinical trial, EQ-5D, and World Health Organization well-being index-5 (WHO-5) questionnaires were obtained at 6-10 weeks and 11-13 months after AMI in 4080 and 806 patients, respectively. We report results from intention-to-treat and on-treatment analyses for the overall population and relevant subgroups using Wilcoxon rank sum test and adjusted ordinal regression analyses. Of the 4080 individuals reporting EQ-5D (median age 64 years, 22% female), 2023 were randomized to beta-blockers. The main outcome, median EQ-5D index score, was 0.94 [interquartile range (IQR) 0.88, 0.97] in the beta-blocker group, and 0.94 (IQR 0.88, 0.97) in the no-beta-blocker group 6-10 weeks after AMI, OR 1.00 [95% CI 0.89-1.13; P > 0.9]. After 11-13 months, results remained unchanged. Findings were robust in on-treatment analyses and across relevant subgroups. Secondary outcomes, EQ-VAS and WHO-5 index score, confirmed these results. CONCLUSION: Among patients after AMI with preserved left ventricular ejection fraction, self-reported quality of life and well-being was not significantly different in individuals randomized to routine long-term beta-blocker therapy as compared to individuals with no beta-blocker use. These results appear consistent regardless of adherence to randomized treatment and across subgroups which emphasizes the need for a careful individual risk-benefit evaluation prior to initiation of beta-blocker treatment.

Intensive early and sustained lowering of non-high-density lipoprotein cholesterol after myocardial infarction and prognosis: the SWEDEHEART registry.

BACKGROUND AND AIMS: Non-high-density lipoprotein cholesterol (HDL-C) provides an estimate of lipid-associated risk and is a secondary treatment target after myocardial infarction (MI). The aim was to study the relationship between non-HDL-C levels after MI and risk of adverse outcomes. METHODS: From the SWEDEHEART registry, 56,262 patients with MI were included. Outcomes were major adverse cardiovascular event (MACE: death, MI, ischaemic stroke), death, and non-fatal MI. Non-HDL-C was assessed at admission, 2 months, and 1 year. Target achievement (<2.2 mmol/L) of non-HDL-C, timing thereof, and outcomes were assessed. RESULTS: During median follow-up of 5.4 years, 9549 had MACE, 5427 died, and 3946 had MI. Long-term hazard ratio (HR) for MACE in the lowest versus the highest quartile of achieved non-HDL-C at 1 year was 0.76 (95% confidence interval 0.71-0.81). Short-term results were consistent also when assessing non-HDL-C levels at 2 months, including early events up to 1 year (HR 0.80, 95% CI 0.68-0.92). Similar results were observed for all outcomes. Patients achieving both early and sustained targets had lowest risk of outcomes (HR 0.80 95% CI 0.74-0.86) versus patients achieving target early or late (HR for both 0.86, 95% CI 0.79-0.93). CONCLUSIONS: The lowest achieved levels both at 2 months and at 1 year of non-HDL-C were associated with better outcome. The lowest risk was observed when target was achieved within 2 months of MI and sustained thereafter. These findings challenge the current stepwise approach for cholesterol lowering after MI which inevitably results in delaying goal attainment and possible harm.

Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction With or Without ST-Segment Elevation.

BACKGROUND: The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non-ST-segment elevation myocardial infarction (NSTEMI). OBJECTIVES: This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI. METHODS: In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete). The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. The key secondary outcome included a composite of cardiovascular death or MI at 1 year. RESULTS: In the overall study population, physiology-guided complete revascularization reduced both primary and key secondary outcomes. The primary outcome occurred in 54 (21.1%) STEMI patients randomized to culprit-only vs 41 (16.2%) STEMI patients of the complete group (HR: 0.75; 95% CI: 0.50-1.13) and in 98 (20.9%) NSTEMI patients randomized to culprit-only vs 72 (15.4%) NSTEMI patients of the complete group (HR: 0.71; 95% CI: 0.53-0.97), with negative interaction testing (P for interaction, 0.846). Similarly, no signal of heterogeneity with respect to the initial clinical presentation was observed for the key secondary endpoint (P for interaction, 0.654). CONCLUSIONS: Physiology-guided complete revascularization, compared with culprit-only revascularization, provided consistent benefit across the whole spectrum of patients with MI. (FIRE [Functional Assessment in Elderly MI Patients With Multivessel Disease]; NCT03772743).

Glycoprotein IIb/IIIa Inhibitors in Acute Myocardial Infarction and Angiographic Microvascular Obstruction: The REVERSE-FLOW Trial.

BACKGROUND AND AIMS: Glycoprotein (GP) IIb/IIIa inhibitors are recommended in acute myocardial infarction (AMI) for bailout treatment in case of angiographic microvascular obstruction (MVO), also termed no-reflow phenomenon, after percutaneous coronary intervention (PCI) with, however, lacking evidence (class IIa, level C). METHODS: The investigator-initiated, international, multicenter REVERSE-FLOW trial randomized 120 patients with AMI and Thrombolysis In Myocardial Infarction flow grade ≤2 after primary PCI to optimal medical therapy with or without GP IIb/IIIa inhibitor. The primary endpoint was infarct size (%LV) assessed by cardiac magnetic resonance (CMR). Secondary endpoints included CMR-derived MVO and 30-day adverse clinical events. The trial is registered with ClinicalTrials.gov: NCT02739711. RESULTS: The population was predominantly male (76.7%) with a median age of 66 years and ST-elevation myocardial infarction in 73.3% of patients. Clinical and angiographic characteristics were well balanced between the cohorts. Patients in the treatment group (n=62) received eptifibatide (n=41) or tirofiban (n=21). Infarct size assessed by CMR imaging was similar in both study groups (25.4% of left ventricular mass [LV] vs. 25.2%LV; p=0.386). However, the number of patients with evidence of CMR-derived MVO (74.5% vs. 92.2%; p=0.017) and the extent of MVO (2.1%LV vs. 3.4%LV; p=0.025) were significantly reduced in the GP IIb/IIIa inhibitor group compared to controls. Thirty-day outcome showed an increased bleeding risk after GP IIb/IIIa inhibitor administration restricted to non-life-threatening bleedings (22.6% vs. 6.9%; p=0.016) without differences in all-cause mortality (4.8% vs. 3.4%; p=0.703). CONCLUSIONS: Bailout GP IIb/IIIa inhibition in AMI patients with angiographic MVO failed to reduce the primary endpoint infarct size but decreased CMR-derived MVO and led to an increase in non-fatal bleeding events.

Reprogramming macrophage metabolism following myocardial infarction: A neglected piece of a therapeutic opportunity.

Given the global prevalence of myocardial infarction (MI) as the leading cause of mortality, there is an urgent need to devise novel strategies that target reducing infarct size, accelerating cardiac tissue repair, and preventing detrimental left ventricular (LV) remodeling. Macrophages, as a predominant type of innate immune cells, undergo metabolic reprogramming following MI, resulting in alterations in function and phenotype that significantly impact the progression of MI size and LV remodeling. This article aimed to delineate the characteristics of macrophage metabolites during reprogramming in MI and elucidate their targets and functions in cardioprotection. Furthermore, we summarize the currently proposed regulatory mechanisms of macrophage metabolic reprogramming and identify the regulators derived from endogenous products and natural small molecules. Finally, we discussed the challenges of macrophage metabolic reprogramming in the treatment of MI, with the goal of inspiring further fundamental and clinical research into reprogramming macrophage metabolism and validating its potential therapeutic targets for MI.

Autophagy in myocardial ischemia and ischemia/reperfusion.

Myocardial infarction (MI) is a life-threatening condition that leads to loss of viable heart tissue. The best way to treat acute MI and limit the infarct size is to re-open the occluded coronary artery and restore the supply of oxygenated and nutrient-rich blood, but reperfusion can cause additional damage. Autophagy is an intracellular process that recycles damaged cytoplasmic components (molecules and organelles) by loading them into autophagosomes and degrading them in autolysosomes. Autophagy is increased in in vivo animal models of permanent ischemia and ischemia/reperfusion but by different molecular mechanisms. While autophagy is protective during permanent ischemia, it is detrimental during ischemia/reperfusion. Its modulation is being investigated as a potential target to reduce reperfusion injury. This review provides a synopsis of the current knowledge about autophagy, summarizes findings specifically in permanent ischemia and ischemia/reperfusion, and briefly discusses the potential implication of experimental findings.

Race, Ethnicity, and Gender Disparities in Acute Myocardial Infarction.

Cardiovascular disease continues to be the leading cause of morbidity and mortality in the United States. Despite advancements in medical care, there remain persistent racial, ethnic, and gender disparity in the diagnosis, treatment, and prognosis of individuals with cardiovascular disease. In this review we seek to discuss differences in pathophysiology, clinical course, and risk profiles in the management and outcomes of acute myocardial infarction and related high-risk states. We also seek to highlight the demographic and psychosocial inequities that cause disparities in acute cardiovascular care.

Apolipoprotein A-I Infusions and Cardiovascular Outcomes in Acute Myocardial Infarction According to Baseline LDL-Cholesterol Levels: The AEGIS-II Trial.

BACKGROUND AND AIMS: In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days versus placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C. METHODS: Overall, 18,219 patients with acute MI, multivessel coronary artery disease, and additional risk factors were randomized to either four weekly infusions of 6 g CSL112 or placebo. This exploratory post-hoc analysis evaluated cardiovascular outcomes by baseline LDL-C in patients prescribed guideline-directed statin therapy at the time of randomization (n=15,731). RESULTS: As baseline LDL-C increased, risk of the primary endpoint at 90 days lowered in those treated with CSL112 compared with placebo. In patients with LDL-C ≥100 mg/dL at randomization, there was a significant risk reduction of cardiovascular death, MI, or stroke in the CSL112 vs. placebo group at 90, 180, and 365 days (hazard ratio 0.69 [0.53-0.90], 0.71 [0.57-0.88], and 0.78 [0.65-0.93]). In contrast, there was no difference between treatment groups among those with LDL-C <100 mg/dL at baseline. CONCLUSIONS: In this population, treatment with CSL112 compared to placebo was associated with a significantly lower risk of recurrent cardiovascular events among patients with a baseline LDL-C ≥100 mg/dL. Further studies need to confirm that CSL112 efficacy is influenced by baseline LDL-C.

Comparison of Ticagrelor with Clopidogrel on Coronary Microvascular Dysfunction Following Acute Myocardial Infarction Using Angiography-Derived Index of Microcirculatory Resistance.

PURPOSE: This research aimed to assess the impact of ticagrelor and clopidogrel on coronary microvascular dysfunction (CMD) and prognosis following acute myocardial infarction (AMI), using the angiography-derived index of microcirculatory resistance (angio-IMR) as a non-invasive assessment tool. METHODS: In this retrospective study, angio-IMR was performed to evaluate CMD before and after dual antiplatelet therapy (DAPT) with either ticagrelor (90 mg twice daily, n = 184) or clopidogrel (75 mg once daily, n = 72). The primary endpoint is the improvement of CMD evaluated by angio-IMR (delta angio-IMR) following DAPT. Secondary endpoints included myocardial reinfarction and readmission for heart failure during 2-year follow-up. RESULTS: Compared with clopidogrel, ticagrelor exhibited a significantly higher delta angio-IMR [- 3.09 (5.14) versus - 1.99 (1.91), P = 0.008], indicating a superior improvement of CMD with ticagrelor treatment. Multivariate Cox regression indicated that ticagrelor treatment was related to a reduced risk of readmission for heart failure [8 (4.3) versus 9 (12.5), adjusted HR = 0.329; 95% CI = 0.116-0.934; P = 0.018] and myocardial reinfarction [7 (3.8) versus 8 (11.1), adjusted HR = 0.349; 95% CI = 0.125-0.975; P = 0.026]. Furthermore, ticagrelor treatment serves as an independent predictor of readmission for heart failure (HR = 0.322; 95% CI = 0.110-0.943; P = 0.039). CONCLUSION: The results of this study indicate a potential association between ticagrelor treatment and improved CMD, as well as a reduced risk of cardiovascular events, including myocardial reinfarction and readmission for heart failure in AMI patients. Further randomized controlled trials are necessary to confirm the potential benefits of ticagrelor on CMD and cardiovascular prognosis. This clinical trial was registered in www. CLINICALTRIALS: gov (NCT05978726).

Routine Extracorporeal Life Support in Infarct-Related Cardiogenic Shock: 1-Year Results of the ECLS-SHOCK Trial.

Extracorporeal life support (ECLS) has been increasingly used in the treatment of severe infarct-related cardiogenic shock in the last decade. The randomised ECLS-SHOCK trial demonstrated no benefit of early routine use on 30-day all-cause death. We herein present mid-term results. At 1-year follow-up, there were no significant differences in all-cause or cardiovascular mortality, neurologic outcome, recurrent myocardial infarction, repeat revascularisation and rehospitalisations for heart failure between ECLS and usual medical care.

Adherence to Cardiac Rehabilitation in Patients with Acute Myocardial Infarction After PCI: A Scoping Review.

Purpose: Cardiac rehabilitation (CR) is a multidisciplinary intervention program aimed at enhancing the physical, psychological, and social functioning of patients with cardiovascular disease. Although CR is cost-effective and reduces mortality and readmission rates, and many patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) do not adhere to CR. This review aimed to synthesize the evidence on adherence to CR in patients with AMI after PCI (AMI-PCI). Patients and Methods: The review was conducted using the methodology proposed by the Joanna Briggs Institute (JBI) to guide reviews and reporting using the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extended for Scoping Reviews (PRISMA-ScR). We searched PubMed, Web of Science, CINAHL, Embase, Ovid, and Scopus databases, and two reviewers independently screened the abstracts and full texts of eligible studies against the inclusion and exclusion criteria. Disagreements were resolved in consultation with a third reviewer. Results: A total of 10 studies were included in the analysis. The results demonstrated that CR reduces the incidence of complications and improves the quality of life of patients with AMI-PCI. However, the CR adherence rate was low, and the factors affecting it are complex and varied, including age, sex, and employment status. Furthermore, interventions to improve adherence in patients with AMI-PCI mainly combined the internet-based interventions, including videoconferencing tele-training, with wearable device monitoring and intelligent management platform follow-up. All these interventions have shown promising results compared with routine care. Conclusion: Adherence to CR in patients with AMI-PCI is generally low, and CR adherence is affected by many factors; however, relevant research designs are rare and simple. Healthcare professionals should pay more attention to adherence to CR in this population and use a variety of interventions to improve it.

Dapagliflozin in Heart Failure and Acute Myocardial Infarction: A Systematic Review of the Association in Diabetic Patients.

This systematic review explores the impact of dapagliflozin on heart failure (HF) and acute myocardial infarction (MI) in patients with type 2 diabetes mellitus. By analyzing recent studies, including both randomized controlled trials (RCTs) and retrospective analyses, this review provides insights into the cardiovascular effects of this sodium-glucose cotransporter 2 (SGLT2) inhibitor. The findings consistently demonstrate the benefits of dapagliflozin in reducing HF-related hospitalizations and improving outcomes for patients with established HF. These positive effects appear to extend beyond glycemic control, suggesting multiple mechanisms of action. The impact of dapagliflozin on acute MI outcomes is less clear, with mixed results across studies. Importantly, dapagliflozin shows promise in improving the quality of life of patients and is generally well-tolerated. The review suggests that dapagliflozin may play a significant role in managing cardiovascular risk in diabetic patients, particularly those with or at risk of HF. While the evidence is encouraging, the review also highlights areas requiring further investigation. These include determining the patient subgroups most likely to benefit from dapagliflozin, elucidating the precise mechanisms underlying its cardioprotective effects, and carrying out long-term outcome studies.

A Comparative Analysis of Single Versus Multiple Arterial Grafts in Coronary Arterial Bypass Grafting: Initial Experience in Iraq.

INTRODUCTION: The global recognition of multiple arterial grafting (MAG) and total arterial grafting (TAG) in coronary artery bypass grafting (CABG) is increasing. However, many centers have not yet adopted these procedures. Our study aims to examine the intraoperative, early postoperative, and two-year follow-up outcomes associated with MAG and TAG in candidates for CABG. The goal is to provide valuable insights into the role of these procedures. METHODS: A prospective comparative study was conducted at Sulaimani Cardiac Hospital to analyze a cohort of 300 patients who underwent CABG surgery between January 2021 and April 2022. Convenience sampling was used to select participants. Prior to surgery, patients underwent comprehensive pre-operative evaluations, with certain CABG types being excluded. The patients were then categorized into three groups based on their surgical approach: single arterial conduit (SA), two arterial conduits (MA), and total arterial revascularization (TA). The standard bypass procedure was performed for all patients, and they were monitored for 30 days, six months, and two years after the surgery. A range of variables, including bypass and cross-clamp times, as well as postoperative complications such as bleeding and stroke, were recorded and analyzed. Statistical Product and Service Solutions (SPSS, version 25; IBM Corp., Armonk, NY) was used for this analysis, with a predetermined significance threshold of p ≤ 0.05. RESULTS: The study included 300 participants who underwent CABG. The participants had an average age of 61.19 ± 4.67 years (95% CI: 36-81) and an average BMI of 27.40 ± 8.4 kg/m² (95% CI: 18-45). Diabetes was present in 40.3% of the patients, and the majority of the participants were male (77.7%). The number of vessels involved in the bypass varied, with two vessels in 21% of cases, three vessels in 65%, and four vessels in 14%. The left internal thoracic artery (LITA) was primarily used for arterial revascularization, and additional arterial conduits were used in 30.3% of cases. Statistical analysis showed significant differences in the number of grafts among patient groups (P = 0.042). However, there were no significant differences in bypass duration, cross-clamp duration, stroke incidence, or in-hospital mortality rates among the groups (P > 0.05). The rates of myocardial infarction (MI) approached significance (P = 0.05), and the mortality rates were comparable over a two-year period after CABG (4.7%) and at shorter intervals. These findings highlight the importance of age and the number of grafts in determining outcomes in CABG patients. CONCLUSION: In a developing nation, the lack of a specialized center for MAG does not hinder the implementation of MAG or TAG. The overall occurrence of complications after CABG is similar across all groups, except for MI. Patients who undergo MAG have higher rates of overall survival compared to those who receive SA and TAG.

Spontaneous Coronary Artery Dissection in the Late Third Trimester of Pregnancy.

Acute coronary syndrome due to a non-atherosclerotic, non-traumatic, or iatrogenic-induced spontaneous coronary artery dissection (SCAD) is a rare clinical condition that affects mostly young women of reproductive age. In this case, we present a 36-week-pregnant, 35-year-old G2P1 woman, with no previous medical history, who was admitted to our hospital with premature pre-labor contractions. During her hospitalization, she underwent a coronary artery percutaneous angiography revealing SCAD of the three coronary vessels, after an episode of acute-onset chest pain, tachypnea, EKG alterations, cardiac enzyme elevation, and bilateral pleural effusions. An emergency cesarean delivery was performed and the patient was transferred to the cardiology intensive care unit. Conservative management was decided and the woman was discharged a few days later.

Macrophage MKL1 contributes to cardiac fibrosis in a mouse model of myocardial infarction.

AIMS: Cardiac fibrosis is characterized by aberrant collagen deposition in the heart. Macrophage polarization or infiltration is the main reason to accelerate the collagen deposition. We attempted to investigate the involvement of MKL1 in macrophages during the development of cardiac fibrosis. MATERIALS AND METHODS: Cardiac fibrosis is induced by myocardial infarction (MI). The MKL1f/f mice were crossed to the Lyz2-cre mice to generate macrophage conditional MKL1 knockout mice (MKL1ΔMφ). In addition, macrophage conditional MKL1 overexpression mice (MKL1Mϕ-OE) were constructed by crossing Lyz2-cre mice to MKL1ΔN200-Rosa26 mice. KEY FINDINGS: MKL1 expression was significantly increased in macrophages of both ischemic cardiomyopathy (ICM) patients and mice induced to develop myocardial infarction. Deletion of MKL1 in macrophages improved the heart function after MI-induced cardiac fibrosis. Consistently, MKL1Mϕ-OE mice displayed more severe cardiac fibrosis and worsened heart function than the control mice after MI. Moreover, administration of a small-molecule MKL1 inhibitor CCG-1423 also decreased the collagen deposition after MI. SIGNIFICANCE: Our data demonstrate that MKL1 in macrophages contributes to cardiac fibrosis pathogenesis and reinforce the notion that targeting MKL1 may yield effective antifibrotic therapeutics in the heart.

Silencing of lncRNA NEAT1 alleviates acute myocardial infarction by suppressing miR-450-5p/ACSL4-mediated ferroptosis.

Ferroptosis is principally initiated by dysregulation of iron metabolism and excessive accumulation of ROS, which exacerbates myocardial injury during acute myocardial infarction (AMI). Previous studies have indeed demonstrated the significant involvement of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) exerts its pleiotropic effects in the pathophysiology of myocardial infarction, heart failure and atherosclerosis by modulating inflammation, apoptosis, and oxidative stress. However, whether and how NEAT1 mediates myocardial ferroptosis remain unknown. In this study, we found that NEAT1 expression was significantly elevated in hypoxic HL-1 cells and AMI mice, while silencing of NEAT1 alleviated lipid peroxidation and myocardial ferroptosis both in vitro and in vivo. Mechanistically, NEAT1 directly sponged miR-450b-5p and negatively regulated its expression. In addition, miR-450b-5p directly targeted Acyl-CoA synthase long-chain family member 4 (ACSL4). Notably, inhibition of miR-450b-5p reversed the role of NEAT1 in AMI mice. Collectively, these findings newly illustrated that NEAT1 acts as a competitive endogenous RNA (ceRNA) of miR-450-5p in AMI. Especially, silencing of NEAT1 effectively ameliorated myocardium ischemia by suppression of ferroptosis via miR-450-5p/ACSL4 pathway, which providing a brand-new therapeutic strategy for myocardial ischemia injury.

A composite patch loaded with 2-Deoxy Glucose facilitates cardiac recovery after myocardial infarction via attenuating local inflammatory response.

Local inflammatory microenvironment in the early stage of myocardial infarction (MI) severely impaired cardiac recovery post-MI. Macrophages play a pivotal role in this process. A classical glycolytic inhibitor, 2-Deoxy-Glucose (2-DG), has been found to regulate the excessive pro-inflammatory macrophage polarization in the infarcted myocardium. This study investigated the effect of 2-DG-loaded chitosan/gelatin composite patch on the infarct microenvironment post-MI and its impact on cardiac repair. The results showed that the 2-DG patch significantly inhibited the expression of inflammatory cytokines, alleviated reactive oxygen species (ROS) accumulation, repressed the proinflammatory polarization of macrophages, attenuated local inflammatory microenvironment in the ischemic hearts, as well as improved cardiac function, reduced scar size, and promoted angiogenesis post-MI. In terms of mechanism, 2-DG exerts anti-inflammatory effects through inhibiting the NF-κB signaling pathway and reducing the assembly and activation of the NLRP3 inflammasome. These findings suggest that 2-DG composite patch may represent a promising therapeutic strategy for cardiac repair after MI.