Pathophysiology of Cardiac Amyloidosis.

Amyloidosis refers to a heterogeneous group of disorders sharing common pathophysiological mechanisms characterized by the extracellular accumulation of fibrillar deposits consisting of the aggregation of misfolded proteins. Cardiac amyloidosis (CA), usually caused by deposition of misfolded transthyretin or immunoglobulin light chains, is an increasingly recognized cause of heart failure burdened by a poor prognosis. CA manifests with a restrictive cardiomyopathy which progressively leads to biventricular thickening, diastolic and then systolic dysfunction, arrhythmias, and valvular disease. The pathophysiology of CA is multifactorial and includes increased oxidative stress, mitochondrial damage, apoptosis, impaired metabolism, and modifications of intracellular calcium balance.

The total xanthones extracted from Gentianella acuta alleviates HFpEF by activating the IRE1α/Xbp1s pathway.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by pulmonary and systemic congestion resulting from left ventricular diastolic dysfunction and increased filling pressure. Currently, however, there is no evidence on effective pharmacotherapy for HFpEF. In this study, we aimed to investigate the therapeutic effect of total xanthones extracted from Gentianella acuta (TXG) on HFpEF by establishing an high-fat diet (HFD) + L-NAME-induced mouse model. Echocardiography was employed to assess the impact of TXG on the cardiac function in HFpEF mice. Haematoxylin and eosin staining, wheat germ agglutinin staining, and Masson's trichrome staining were utilized to observe the histopathological changes following TXG treatment. The results demonstrated that TXG alleviated HFpEF by reducing the expressions of genes associated with myocardial hypertrophy, fibrosis and apoptosis. Furthermore, TXG improved cardiomyocyte apoptosis by inhibiting the expression of apoptosis-related proteins. Mechanistic investigations revealed that TXG could activate the inositol-requiring enzyme 1α (IRE1α)/X-box-binding protein 1 (Xbp1s) signalling pathway, but the knockdown of IRE1α using the IRE1α inhibitor STF083010 or siRNA-IRE1α impaired the ability of TXG to ameliorate cardiac remodelling in HFpEF models. In conclusion, TXG alleviates myocardial hypertrophy, fibrosis and apoptosis through the activation of the IRE1α/Xbp1s signalling pathway, suggesting its potential beneficial effects on HFpEF patients.

Correlation between elevated HCLS1 levels and heart failure: A diagnostic biomarker.

The correlation between hematopoietic cell-specific lyn substrate 1 (HCLS1) expression levels and heart failure (HF) remains unclear. HF datasets GSE192886 and GSE196656 profiles were generated from GPL24676 and GPL20301 platforms in gene expression omnibus (GEO) database and differentially expressed genes (DEGs) were obtained, which was followed by weighted gene co-expression network analysis, protein-protein interaction (PPI) networks, functional enrichment analysis and comparative toxicogenomics database (CTD) analysis. Heatmaps of gene expression levels were plotted. TargetScan was used to screen miRNAs regulating central DEGs. A total of 500 DEGs were found and mainly concentrated in leukocyte activation, protein phosphorylation, and protein complexes involved in cell adhesion, PI3K Akt signaling pathway, Notch signaling pathway, and right ventricular cardiomyopathy. PPI network identified 15 core genes (HCLS1, FERMT3, CD53, CD34, ITGAL, EP300, LYN, VAV1, ITGAX, LEP, ITGB1, IGF1, MMP9, SMAD2, RAC2). Heatmap shows that 4 genes (EP300, CD53, HCLS1, LYN) are highly expressed in HF tissue samples. We found that 4 genes (EP300, CD53, HCLS1, LYN) were associated with heart diseases, cardiovascular diseases, edema, rheumatoid arthritis, necrosis, and inflammation. HCLS1 is highly expressed in HF and maybe its target.

The Role of Scintigraphy with Bone Radiotracers in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The paradigm of this condition has transformed, since CA is increasingly recognized as a relatively prevalent cause of heart failure. Cardiac scintigraphy with bone tracers is the unique noninvasive technique able to confirm CA without performing tissue biopsy or advanced imaging tests. A moderate-to-intense myocardial uptake (Perugini grade ≥2) associated with the absence of a monoclonal component is greater than 99% specific for ATTR-CA, while AL-CA confirmation requires tissue biopsy.

Aerobic exercise-induced HIF-1α upregulation in heart failure: exploring potential impacts on MCT1 and MPC1 regulation.

BACKGROUND: The terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia. METHODS: The experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection. RESULTS: Our results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p < 0.05), MCT1 (p < 0.01) and MPC1 (p < 0.05) proteins compared to HF group rats. Moreover, pharmacological inhibition of HIF-1α in hypoxic H9c2 cells dramatically downregulated MCT1 and MPC1 protein expression. This phenomenon is consistent with knockdown of HIF-1α at the gene level. CONCLUSION: The findings propose that long-term aerobic exercise training, as a non- pharmacological treatment, is efficient enough to debilitate the disease process, improve the pathological phenotype, and reinstate cardiac function in HF rats. This benefit is most likely due to activation of myocardial HIF-1α and upregulation of MCT1 and MPC1.

Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis.

Semaglutide, a glucagon-like peptide-1 receptor agonist, is clinically used as a glucose-lowering and weight loss medication due to its effects on energy metabolism. In heart failure, energy production is impaired due to altered mitochondrial function and increased glycolysis. However, the impact of semaglutide on cardiomyocyte metabolism under pressure overload remains unclear. Here we demonstrate that semaglutide improves cardiac function and reduces hypertrophy and fibrosis in a mouse model of pressure overload-induced heart failure. Semaglutide preserves mitochondrial structure and function under chronic stress. Metabolomics reveals that semaglutide reduces mitochondrial damage, lipid accumulation, and ATP deficiency by promoting pyruvate entry into the tricarboxylic acid cycle and increasing fatty acid oxidation. Transcriptional analysis shows that semaglutide regulates myocardial energy metabolism through the Creb5/NR4a1 axis in the PI3K/AKT pathway, reducing NR4a1 expression and its translocation to mitochondria. NR4a1 knockdown ameliorates mitochondrial dysfunction and abnormal glucose and lipid metabolism in the heart. These findings suggest that semaglutide may be a therapeutic agent for improving cardiac remodeling by modulating energy metabolism.

Optimized new Shengmai powder inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway.

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder (, ONSMP) on myocardial fibrosis in heart failure (HF) based on rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinases (ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham (n = 10) and operation (n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low (L), medium (M), and high (H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen (COL) I and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the mRNA levels of COL I, COL Ⅲ, α-smooth muscle actin (α-SMA), and c-Fos proto-oncogene (c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor (p-ELK1), p-c-Fos, α-SMA, COL I, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL I/Ⅲ content, down-regulate the mRNA of COL I/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/ 2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

Mechanism of Astragalus membranaceus (Huangqi, HQ) for treatment of heart failure based on network pharmacology and molecular docking.

Heart failure is a leading cause of death in the elderly. Traditional Chinese medicine, a verified alternative therapeutic regimen, has been used to treat heart failure, which is less expensive and has fewer adverse effects. In this study, a total of 15 active ingredients of Astragalus membranaceus (Huangqi, HQ) were obtained; among them, Isorhamnetin, Quercetin, Calycosin, Formononetin, and Kaempferol were found to be linked to heart failure. Ang II significantly enlarged the cell size of cardiomyocytes, which could be partially reduced by Quercetin, Isorhamnetin, Calycosin, Kaempferol, or Formononetin. Ang II significantly up-regulated ANP, BNP, ß-MHC, and CTGF expressions, whereas Quercetin, Isorhamnetin, Calycosin, Kaempferol or Formononetin treatment partially downregulated ANP, BNP, ß-MHC and CTGF expressions. Five active ingredients of HQ attenuated inflammation in Ang II-induced cardiomyocytes by inhibiting the levels of TNF-α, IL-1ß, IL-18 and IL-6. Molecular docking shows Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol can bind with its target protein ESR1 in a good bond by intermolecular force. Quercetin, Calycosin, Kaempferol or Formononetin treatment promoted the expression levels of ESR1 and phosphorylated ESR1 in Ang II-stimulated cardiomyocytes; however, Isorhamnetin treatment had no effect on ESR1 and phosphorylated ESR1 expression levels. In conclusion, our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HQ against heart failure. Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol might be the primary active ingredients of HQ, dominating its cardioprotective effects against heart failure through regulating ESR1 expression, which provided a basis for the clinical application of HQ to regulate cardiac hypertrophy and heart failure.

[Mechanisms of NLRP3 inflammasome-mediated pyroptosis in chronic heart failure and research progress in traditional Chinese medicine].

Chronic heart failure(CHF) is a severe cardiovascular disease characterized by a complex pathogenesis involving myocardial structural and functional abnormalities and the activation of inflammatory responses. The NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome, acting as a sensor for inflammatory cells, plays a pivotal role in the development of CHF. Research indicates that the activation of the NLRP3 inflammasome can induce inflammatory responses, leading to cardiac inflammation and impairing myocardial function, and it is correlated with the severity of CHF. Traditional Chinese medicine(TCM) has garnered increasing attention as a traditional therapeutic approach in recent years. Various TCM drugs and treatment methods have exhibited potential efficacy in suppressing inflammatory responses, alleviating myocardial cell pyroptosis, improving myocardial structure and function, and inhibiting myocardial fibrosis. Several TCM drugs and their extracts have been utilized in CHF treatment, with mechanisms potentially involving the inhibition of NLRP3 inflammasomes and the mitigation of inflammatory responses. The article provided an overview of the composition, structural characteristics, initiation, and activation modes of the NLRP3 inflammasome, its mechanisms in CHF, and the research progress of TCM in CHF treatment. It aims to offer references and foundations for a deeper understanding of CHF pathogenesis and subsequent development of new therapeutic strategies.

Effects of dapagliflozin against streptozotocin and isoproterenol-induced heart failure via investigating NLRP3 and PPAR-γ signaling.

Heart failure is a condition in which the heart's one or both ventricles are unable to either receive an adequate amount of blood or eject an adequate amount of blood. Diabetes is considered one of the major risk factors for cardiovascular diseases. The current research is designed to evaluate the cardioprotective effects of dapagliflozin in streptozotocin and isoproterenol-induced comorbid rats. The COX-2, TNF-α, NF-КB, NLRP3, PPAR-γ, CKMB, TROP-I, AR, GP and SGLT were docked against dapagliflozin, propranolol and metformin. Dapagliflozin restored adequate blood flow and halted myofibril damage. Moreover, it's evident from this study that dapagliflozin significantly decreased serum concentration of various blood markers, decreased relative growth rate and QT interval prolongation, as compared to the negative control group. However, it improved the ventricular ejection fraction in rats of the treatment group. The GST, GSH and CAT levels were increased, as compared to normal. On the contrary, a decrease in LPO concentrations was observed. Evaluation of the coronal section of heart tissues showed the anti-inflammatory expressions evaluated through H & E staining and immunohistochemical techniques and with ELISA and PCR. In a nutshell, dapagliflozin reverses myocardial necrosis and apoptosis.

Mitochondria transplantation alleviates cardiomyocytes apoptosis through inhibiting AMPKα-mTOR mediated excessive autophagy.

The disruption of mitochondria homeostasis can impair the contractile function of cardiomyocytes, leading to cardiac dysfunction and an increased risk of heart failure. This study introduces a pioneering therapeutic strategy employing mitochondria derived from human umbilical cord mesenchymal stem cells (hu-MSC) (MSC-Mito) for heart failure treatment. Initially, we isolated MSC-Mito, confirming their functionality. Subsequently, we monitored the process of single mitochondria transplantation into recipient cells and observed a time-dependent uptake of mitochondria in vivo. Evidence of human-specific mitochondrial DNA (mtDNA) in murine cardiomyocytes was observed after MSC-Mito transplantation. Employing a doxorubicin (DOX)-induced heart failure model, we demonstrated that MSC-Mito transplantation could safeguard cardiac function and avert cardiomyocyte apoptosis, indicating metabolic compatibility between hu-MSC-derived mitochondria and recipient mitochondria. Finally, through RNA sequencing and validation experiments, we discovered that MSC-Mito transplantation potentially exerted cardioprotection by reinstating ATP production and curtailing AMPKα-mTOR-mediated excessive autophagy.

Upregulated dual oxidase 1-induced oxidative stress and caspase-1-dependent pyroptosis reflect the etiologies of heart failure.

BACKGROUND: Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was designed to evaluate the potential role of DUOX1 in heart failure. MATERIALS AND METHODS: AC16 cells were treated with 2 µmol/L of doxorubicin (DOX) for 12, 24, and 48 h to construct a heart failure model. DUOX1 overexpression and silencing in AC16 cell were established. DUOX1 expression was detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Pyroptosis and reactive oxygen species (ROS) production were measured by flow cytometry. RESULTS: Increased DUOX1 expression levels were observed after DOX treatment for 24 h in AC16 cells. DUOX1 silencing inhibited DOX-induced pyroptosis and ROS production. The release of IL-1ß, IL-18, and lactate dehydrogenase (LDH), and expression levels of pyroptosis-related proteins were also decreased. DUOX1 overexpression increased pyroptosis, ROS production, IL-1ß, IL-18, and LDH release, and pyroptosis-related protein expression. N-acetyl-cysteine (NAC) significantly reversed DUOX1-induced pyroptosis, ROS, and related factors. CONCLUSION: These results suggest that DUOX1-derived genotoxicity could promote heart failure development. In the process, oxidative stress and pyroptosis may be involved in the regulation of DUOX1 in heart failure.

Circular RNAs: a small piece in the heart failure puzzle.

Cardiovascular disease, specifically heart failure (HF), remains a significant concern in the realm of healthcare, necessitating the development of new treatments and biomarkers. The RNA family consists of various subgroups, including microRNAs, PIWI-interacting RNAs (piRAN) and long non-coding RNAs, which have shown potential in advancing personalized healthcare for HF patients. Recent research suggests that circular RNAs, a lesser-known subgroup of RNAs, may offer a novel set of targets and biomarkers for HF. This review will discuss the biogenesis of circular RNAs, their unique characteristics relevant to HF, their role in heart function, and their potential use as biomarkers in the bloodstream. Furthermore, future research directions in this field will be outlined. The stability of exosomal circRNAs makes them suitable as biomarkers, pathogenic regulators, and potential treatments for cardiovascular diseases such as atherosclerosis, acute coronary syndrome, ischemia/reperfusion injury, HF, and peripheral artery disease. Herein, we summarized the role of circular RNAs and their exosomal forms in HF diseases.

First-in-man use of a cardiovascular cell-derived secretome in heart failure. Case report.

BACKGROUND: There is increased evidence that the effects of stem cells can mostly be duplicated by administration of their secretome which might streamline the translation towards the clinics. METHODS: The 12-patient SECRET-HF phase 1 trial has thus been designed to determine the feasibility and safety of repeated intravenous injections of the extracellular vesicle (EV)-enriched secretome of cardiovascular progenitor cells differentiated from pluripotent stem cells in severely symptomatic patients with drug-refractory left ventricular (LV) dysfunction secondary to non-ischemic dilated cardiomyopathy. Here we report the case of the first treated patient (baseline NYHA class III; LV Ejection Fraction:25%) in whom a dose of 20 × 109 particles/kg was intravenously infused three times three weeks apart. FINDINGS: In addition to demonstrating the feasibility of producing a cardiac cell secretome compliant with Good Manufacturing Practice standards, this case documents the excellent tolerance of its repeated delivery, without any adverse events during or after infusions. Six months after the procedure, the patient is in NYHA Class II with improved echo parameters, a reduced daily need for diuretics (from 240 mg to 160 mg), no firing from the previously implanted automatic internal defibrillator and no alloimmunization against the drug product, thereby supporting its lack of immunogenicity. INTERPRETATION: The rationale underlying the intravenous route is that the infused EV-enriched secretome may act by rewiring endogenous immune cells, both circulating and in peripheral organs, to take on a reparative phenotype. These EV-modified immune cells could then traffic to the heart to effect tissue repair, including mitigation of inflammation which is a hallmark of cardiac failure. FUNDING: This trial is funded by the French Ministry of Health (Programme Hospitalier de Recherche CliniqueAOM19330) and the "France 2030" National Strategy Program (ANR-20-F2II-0003). It is sponsored by Assistance Publique-Hôpitaux de Paris.

Chronic circadian rhythm disorder induces heart failure with preserved ejection fraction-like phenotype through the Clock-sGC-cGMP-PKG1 signaling pathway.

Emerging evidence has documented that circadian rhythm disorders could be related to cardiovascular diseases. However, there is limited knowledge on the direct adverse effects of circadian misalignment on the heart. This study aimed to investigate the effect of chronic circadian rhythm disorder on heart homeostasis in a mouse model of consistent jetlag. The jetlag model was induced in mice by a serial 8-h phase advance of the light cycle using a light-controlled isolation box every 4 days for up to 3 months. Herein, we demonstrated for the first time that chronic circadian rhythm disorder established in the mouse jetlag model could lead to HFpEF-like phenotype such as cardiac hypertrophy, cardiac fibrosis, and cardiac diastolic dysfunction, following the attenuation of the Clock-sGC-cGMP-PKG1 signaling. In addition, clock gene knock down in cardiomyocytes induced hypertrophy via decreased sGC-cGMP-PKG signaling pathway. Furthermore, treatment with an sGC-activator riociguat directly attenuated the adverse effects of jetlag model-induced cardiac hypertrophy, cardiac fibrosis, and cardiac diastolic dysfunction. Our data suggest that circadian rhythm disruption could induce HFpEF-like phenotype through downregulation of the clock-sGC-cGMP-PKG1 signaling pathway. sGC could be one of the molecular targets against circadian rhythm disorder-related heart disease.

Sacubitril/valsartan ameliorates cardiac function and ventricular remodeling in CHF rats via the inhibition of the tryptophan/kynurenine metabolism and inflammation.

Sacubitril/valsartan has been highly recognized as a treatment for Chronic heart failure (CHF). Its potential cardioprotective benefits and mechanisms, however, remain to be explored. Metabolomics can be used to identify the metabolic characteristics and related markers, as well as the influence of drugs, thereby opening up the new mechanism for sacubitril/valsartan therapy in CHF disease. In this study, the ligation of left anterior descending and exhaustive swimming were used to induce a rat model of CHF after myocardial infarction. The efficacy was appraised with echocardiography, serum NT-proBNP, and histopathologica. UPLC-Q/TOF-MS combined with multivariate statistical analysis approach were used to analyze the effect of sacubitril/valsartan on CHF rats. RT-qPCR and western blot were performed to investigate the tryptophan/kynurenine metabolism pathway. Accordingly, the basal cardiac function were increased, while the serum NT-proBNP and collagen volume fraction decreased in CHF rats with sacubitril/valsartan. Sacubitril/valsartan regulated the expression of kynurenine et.al 8 metabolomic biomarkers in CHF rats serum, and it contributed to the cardioprotective effects through tryptophan metabolism pathway. In addition, the mRNA and protein expression of the indoleamine 2,3-dioxygenase (IDO) in the myocardial tissue of CHF rats, were down-regulated by sacubitril/valsartan, which was the same with the IL-1ß, IFN-γ, TNF-α, COX-2, and IL-6 mRNA expression, and IL-1ß, IFN-γ, and TNF-α expression in serum. In conclusion, sacubitril/valsartan can ameliorate cardiac function and ventricular remodeling in CHF rats, at least in part through inhibition of tryptophan/kynurenine metabolism.

DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure.

DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

In vivo phage display identifies novel peptides for cardiac targeting.

Heart failure remains a leading cause of mortality. Therapeutic intervention for heart failure would benefit from targeted delivery to the damaged heart tissue. Here, we applied in vivo peptide phage display coupled with high-throughput Next-Generation Sequencing (NGS) and identified peptides specifically targeting damaged cardiac tissue. We established a bioinformatics pipeline for the identification of cardiac targeting peptides. Hit peptides demonstrated preferential uptake by human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and immortalized mouse HL1 cardiomyocytes, without substantial uptake in human liver HepG2 cells. These novel peptides hold promise for use in targeted drug delivery and regenerative strategies and open new avenues in cardiovascular research and clinical practice.

4-hydroxysesamin protects rat with right ventricular failure due to pulmonary hypertension by inhibiting JNK/p38 MAPK signaling.

The specific mechanism of 4-hydroxysesamin (4-HS), a modification of Sesamin, on right ventricular failure due to pulmonary hypertension (PH) is ominous. By creating a rat model of PH in vivo and a model of pulmonary artery smooth muscle cell (PASMC) hypoxia and inflammation in vitro, the current work aimed to investigate in depth the molecular mechanism of the protective effect of 4-HS. In an in vitro model of hypoxia PASMC, changes in cell proliferation and inflammatory factors were detected after treatment with 4-HS, followed by changes in the JNK/p38 MAPK signaling pathway as detected by Western blot signaling pathway. The findings demonstrated that 4-HS was able to minimize PASMC cell death, block the JNK/p38 MAPK signaling pathway, and resist the promoting effect of hypoxia on PASMC cell proliferation. Following that, we found that 4-HS could both mitigate the right ventricular damage brought on by MCT and had a protective impact on rats Monocrotaline (MCT)-induced PH in in vivo investigations. The key finding of this study is that 4-HS may protect against PH by inhibiting the JNK/p38 MAPK signaling pathway.