IQ-RKT Formulation mitigates cardiomyocytes injury by targeting AGEs-RAGE-ROS-dependent TRAF3IP2/JNK apoptotic nexus in diabetes.

Sinomenine ameliorates myocardial ischemia/reperfusion injury by inhibiting mitochondrial oxidative stress-mediated PANoptosis and ferroptosis via α7nAChR.

TRIM28 aggravates myocardial infarction-induced cardiomyocyte apoptosis through regulating the stability of ATF5 via ubiquitination and SUMOylation.

Autophagy-driven CCL7+ monocyte terminal differentiation program fuels CD8+ T cell-mediated cardiac injury in Sepsis.

MEK inhibitor induces cardiac complications by preventing ZMYND8-mediated ubiquitination and proteasomal degradation of HMGB1.

Cordycepin alleviates sepsis-induced cardiomyopathy by attenuating mitochondrial oxidative stress and apoptosis through modulation of the PI3K/Akt/mTOR pathway.

Naringenin attenuates inflammation and apoptosis in lipopolysaccharide-induced H9c2 cardiomyocytes

Pre-treatment with sevoflurane alleviates hypoxia-reoxygenation-induced cardiomyocyte damage through PAX8-AS1-targeted miR-145-5p.

Bioactive cardiac ECM hydrogel sequentially released VEGF and Ang-1 mimic peptides to promote the recovery of myocardial infarction.

Cornus officinalis total glycosides modulate inflammatory response and inhibit the JAK1/STAT3 pathway within a preclinical rat model of cardiac ischemia/reperfusion-induced injury.

Targeting LUM-mediated inflammatory cell communication and fibroblast apoptosis with SFI in Heart Failure.

Breast cancer susceptibility gene 2 upregulation alleviated cardiac hypertrophy in angiotensin II-treated mice.

BDH1 regulates cardiomyocyte apoptosis and diabetic cardiomyopathy by modulating mitochondrial dynamics and attenuating oxidative stress.

The myocardial infarction-associated transcript (MIAT), a conserved long noncoding RNA, is upregulated in failing human and murine hearts. We previously demonstrated that systemic or cardiomyocyte (CM)-restricted ablation of MIAT in mice attenuated maladaptive cardiac remodeling following myocardial infarction by suppressing the expression of proapoptotic and profibrotic genes. Despite growing evidence from human and rodent studies implicating MIAT in heart failure, the upstream regulatory pathways controlling its expression remain poorly defined. We hypothesized that MIAT is regulated either by β-arrestin1-mediated β1-adrenergic receptor protective signaling or by the transcription factor BTB domain and CNC homolog 2 (BACH2), which is downregulated in failing human and murine hearts. In this study, we show that treatment with the β-blocker carvedilol downregulates cardiac MIAT via β1-adrenergic receptor/β-arrestin1 signaling and concurrently upregulates BACH2. Mechanistically, our co-immunoprecipitation and electrophoretic mobility shift assays reveal that BACH2 forms a nuclear complex with β-arrestin1 and binds to conserved elements within the MIAT promoter. Using primary adult human cardiac fibroblasts (CFs) as well as human and rodent CMs, we further show that BACH2 represses profibrotic and proapoptotic MIAT expression, thereby inhibiting CF activation and CM apoptosis. Together, these findings identify a novel regulatory axis involving β1-adrenergic receptor/β-arrestin1 signaling, BACH2, and MIAT, highlighting its critical role in maladaptive cardiac remodeling.

The mechanism and clinical research of vagus nerve electrical stimulation in the treatment of myocardial ischemia-reperfusion injury.

Macrophage-mediated angiogenesis and lymphangiogenesis after myocardial infarction (MI) are essential for restoring cardiac perfusion and lymphatic drainage, thereby limiting cardiac tissue ischemia, edema, and fibrosis. Shuxuening injection (SXNI) is commonly used in the treatment of cardiovascular diseases in clinical practice, but its mechanism of action in mitigating cardiac remodeling after MI is still unclear. This study aimed to investigate the effect of SXNI on ventricular remodeling after MI and to clarify its mechanism of action. SXNI were administered at doses of 1.05 (low-dose), 2.1 (clinical equivalent-dose), and 4.2 (high-dose) mL/kg/day over a 4-week period by using a rat MI model. Pharmacodynamic assessments encompassed cardiac function, infarct size, and fibrosis areas. Angiogenesis and lymphangiogenesis were assessed via immunohistochemical staining, western blotting, qRT-PCR, and ELISA. Assessment of cardiac edema and inflammatory status used gravimetry and ELISA. CCK-8, scratch wound, and tube formation assays were conducted to detect the direct and indirect (macrophage-mediated) effects of SXNI on HUVECs and SVEC4-10 cells. Western blotting examined the underlying mechanisms. The chemical composition of SXNI was determined by ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UPLC-QE-MS). Key components of SXNI capable of binding to VEGF-A/VEGF-C were screened via molecular docking. The effects of these components on VEGF-A and VEGF-C levels in macrophages were then detected using qRT-PCR and ELISA. In MI rats, SXNI significantly enhanced cardiac function, reduced infarct size, and suppressed cardiomyocyte apoptosis. SXNI activated the VEGF-A/VEGFR2 and VEGF-C/VEGFR3 signaling pathways, thereby promoting post-MI angiogenesis and lymphangiogenesis, consequently decreasing cardiac edema, inflammation, and dysfunction. Direct intervention with SXNI does not affect the viability or tube formation ability of HUVEC or SVEC4-10 cells. However, SXNI promoted the secretion of angiogenic factors by Raw264.7 cells. SXNI-induced macrophage stimulation indirectly enhanced the proliferation, migration, and tube formation of HUVECs and SVEC4-10 cells, thereby activating VEGFR2-mediated signals (AKT/ERK1/2) and VEGFR3-mediated signals (AKT/ERK1/2) in vitro, facilitating angiogenesis and lymphangiogenesis. Seventy chemical components were identified using UPLC-QE-MS mass spectrometry. Molecular docking results suggest that ginkgolide A, ginkgolide B, rutin and quercetin 3-neohesperidoside may bind to VEGF-A and VEGF-C proteins. Subsequent cellular experiments confirmed that these compounds could regulate the expression levels of VEGF-A and VEGF-C in macrophages. SXNI activates macrophages to secrete VEGFs, such as VEGF-A and VEGF-C, which in turn activate the VEGFR2 and VEGFR3 signaling pathways in endothelial cells and lymphatic endothelial cells, thereby promoting angiogenesis and lymphangiogenesis and ameliorating ventricular remodeling. The key active ingredients in SXNI may be ginkgolide A, ginkgolide B, rutin and quercetin 3-neohesperidoside. This work provides valuable clinical evidence supporting its use in MI patient treatment.

Myocardial infarction (MI) is a severe cardiovascular disorder characterized by an irreversible myocardial necrosis caused by acute ischemia. The typical manifestations of MI include persistent substernal chest pain, dyspnea, nausea, vomiting, and diaphoresis. Astragaloside IV (AS-IV), a major bioactive component of Astragalus membranaceus, has been extensively investigated over the past decade. Evidence indicates that AS-IV exerts multifaceted protective effects against MI by modulating various key signaling pathways involved in anti-inflammatory, anti-oxidative stress, and antifibrotic activities, the inhibition of cardiomyocyte apoptosis, and the maintenance of mitochondrial homeostasis. These pathways include TLR4/NF-[Formula: see text]B, PI3K/AKT, TGF-[Formula: see text]/Smad2, ROS/caspase-1/GSDMD, Wnt/[Formula: see text]-catenin, AMPK/ACSS2/PPAR[Formula: see text], Sirt3/Drp1, and PINK1/Parkin. Although mechanistic studies have substantially advanced, the clinical application of AS-IV in MI remains in the exploratory stage. Further well-designed clinical trials are necessary in order to validate the therapeutic efficacy and safety of AS-IV, thereby facilitating its translation from experimental research to clinical practice, and offering new insights and potential strategies for MI management.

1,3-Butanediol enhances autophagy via PI3K/Akt/FOXO3 pathway to ameliorate cardiac remodeling post-myocardial infarction.

SIRT1 exhibited a protective role in myocardial ischemia/reperfusion injury (MI/RI), but the related mechanisms remained unclear. In this study, the regulation of SIRT1 on neddylation modification in MI/RI was explored. H9C2 cells underwent hypoxia and reoxygenation (H/R) to mimic MI/RI in vitro, and C57BL6 mice were employed to establish MI/RI model for the in vivo experiments. Mass spectrometry analysis was employed to screen the possible modified substrates of NEDD8; Western blot was performed to detect protein level; CCK8 was performed to assess cell viability; flow cytometry, TUNEL, and Cardiac Troponin T (cTNT) double staining were performed to assess cardiomyocytes apoptosis; TTC and HE staining were performed to assess infarction area and pathological changes of cardiac tissues in MI/RI mice, respectively. MLN4924 (an inhibitor of NEDD8-activating enzyme (NAE)) significantly reversed the elevated NEDD8 conjugated protein (p < 0.001) and reduced SIRT1 protein levels (p < 0.001) induced by H/R in H9C2 cells. Dead-box helicase 5 (DDX5) was screened as the possible modified substrate of NEDD8 via mass spectrometry. H/R further reduced DDX5 protein level (p < 0.001) and increased DDX5 neddylation in H9C2 cells, while which were reversed by MLN4924 or LV-SIRT1 (p < 0.05). Also, SIRT1 increased DDX5 protein level by enhancing DDX5 stability via reducing its neddylation. Functionally, hypoxia decreased cell viability (p < 0.001) and increased cell apoptosis (p < 0.001) and ROS level (p < 0.001) in H9C2 cells, whereas they were all reversed by LV-SIRT1 (p < 0.05, p < 0.001) or LV-DDX5 (p < 0.05, p < 0.001). The in vivo experiments revealed that LV-DDX5 reversed the increased infarction area (p < 0.05), necrotic myocardial fibers and cardiomyocytes apoptosis (p < 0.001) in MI/RI mice. These results suggested that SIRT1 increased DDX5 protein level to reduce cardiomyocytes apoptosis and ROS level via the inhibition of DDX5 neddylation, thus alleviating MI/RI.

The clinical use of doxorubicin (DOX) as a chemotherapeutic agent is limited by its cardiotoxic effects. Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, has been increasingly recognized as an important regulator of cardiovascular disease. However, its role in doxorubicin-induced cardiotoxicity remains unknown. Therefore, the objective of this study is to investigate the role and mechanism of FGF13 in doxorubicin-induced cardiac injury. C57BL/6 mice are used to establish Dox-induced cardiotoxicity models. The results reveal that mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening are decreased in the DOX group. In contrast, Fgf13 deficiency mitigates doxorubicin-mediated cardiotoxicity, as indicated by increased mouse weight, cardiomyocyte cross-sectional area, ejection fraction and fractional shortening. Mechanistically, the protein expressions of bax and cleaved caspase 3 are elevated in the DOX-treated group, along with decreased JC-1 fluorescence intensity and bcl-2 expression, whereas Fgf13 knockout prevents these alterations. In addition, Parkin, but not p53, interacts with FGF13 and is upregulated in response to Fgf13 deficiency in a mouse model of doxorubicin-induced cardiotoxicity. Overall, Fgf13 knockout attenuates doxorubicin-induced cardiomyocyte apoptosis and mitochondrial damage through the modulation of Parkin, indicating that FGF13 may serve as a promising therapeutic target for DOX-induced cardiotoxicity.