Cardiac Protective Effects Research Articles

SGLT2 inhibitors - A novel treatment for congestive heart failure and chronic kidney disease

SGLT2 inhibitors increase renal excretion of sodium and glucose by blocking the SGLT2 transporters in the proximal tubule. Not only do they lower blood sugars levels but also have positive effects on blood pressure and weight. They lead to more efficient energy metabolism in the heart and kidneys, increase the production of red blood cells and decrease fibrosis and inflammation in the heart and the kidneys. Large double blind randomized trials have shown both cardiac and renal protective effects. Patient with heart failure, both with reduced and preserved ejection fraction have shown to benefit from treatment with SGLT2 inhibitors. They have lower risk of death due to cardiovascular causes and decreased risk of hospitalization because of heart failure compared to patient treated with placebo both with and without diabetes type 2. SGLT2 inhibitors are shown to decrease risk of chronic kidney disease stage 5 and dialysis, death due of cardiovascular events and doubling of serum creatinine in patients with chronic kidney disease both with and without diabetes type 2. They are now recommended for treatment of heart failure and chronic kidney disease with the highest evidence grade. SGLT2 inhibitors do not increase risk of hypoglycemia or acute kidney injury but do have a serious uncommon adverse effect that are normoglycemic ketoacidosis and Fournier's gangrene that physicians need to be alert to.

Isoliquiritin targeting m5C RNA methylation improves mitophagy in doxorubicin-induced myocardial cardiotoxicity

BackgroundDoxorubicin (DOX)-induced myocardial cardiotoxicity (DIC) severely limits its clinical application, and there is no optimal therapeutic agent available. Recent studies revealed that activation of BNIP3-mediated mitophagy and the inhibition of m5C RNA methylation played a crucial role in DIC. Isoliquiritin (ISL) has remarkable cardiac protective effect. But its potential mechanisms against DIC still remains unknown. PurposeTo investigate the therapeutic effect and potential mechanism of Isoliquiritin(ISL) on doxorubicin(DOX)-induced myocardial cardiotoxicity(DIC). MethodsBioinformatics analyses and network pharmacology were carried out to identify effective target of ISL against DIC. Molecular docking and surface-plasmon resonance (SPR) were used to confirm the predict. The mechanism of ISL regulating mitophagy through M5C methylation to improve DIC was demonstrated in vitro and in vivo experiments. The methylation modification was verified by MeRIP-qPCR. Cell model of DIC was constructed to evaluate mitochondrial function by measuring cell viability, myocardial enzyme level, mitochondrial quality, mCherry-EGFP analysis and TEM morphometry with the application of mitophagy inhibitor (Baf A1) and inducer (CCCP). Myocardial injury in mice with DIC was assessed by survival rate, myocardial enzyme level, HE staining, echocardiography and detection of mitophagy markers. ResultsThe decreased level of m5C writer TRDMT1 and mitochondrial marker (BNIP3) were chosen for the research. After the docking and SPR verification between ISL and TRDMT1, the improvement of ISL on TRDMT1 and TRDMT1-associated m5C level of BNIP3 was identified. In vitro and in vivo experiments showed that the cardiac markers, heart function, and mitochondrial function were recovered after ISL application. Meanwhile, the results manifested that there was blocked autophagy flow indicated by mCherry-EGFP analysis, then the suppressed mitophagy caused the mitochondria damage associated cell death. ISL could alleviate the autophagy block, and Baf A1 couldn't influnce the ISL effect. Compared to CCCP group, Mitochondrial maker TOMM20 significantly elevated treated with both CCCP and DOX, indicating that DOX impaired mitophagy for clearing damaged mitochondrial proteins. After ISL treated, a higher level of co-localization between mitochondrial and BNIP3 was observed, inducing restoration of mitochondrial function. ConclusionThis study showed that ISL may exert cardioprotective role restoring BNIP3-mediated mitophagy by targeting TRDMT1 to alleviate DOX-induced macro-autophagy-dependent protein homeostasis and acquired blocking of mitophagy, providing a new idea for the clinical treatment of DIC.

The NLRP3-inflammasome inhibitor MCC950 improves cardiac function in a HFpEF mouse model

Heart failure with preserved ejection fraction (HFpEF) is posing a significant medical challenge due to its growing prevalence, high hospitalization rates and limited response to current treatment options. Accumulating evidence suggests that a comorbidity-driven systemic pro-inflammatory state, including activation of the NLRP3 inflammasome, contributes to the pathogenesis of HFpEF. This study aimed to investigate the potential cardiac protective effects of the selective NLRP3 inhibitor MCC950, in a mouse model of HFpEF. HFpEF was obtained in 18–22 months old female mice using high-fat diet (HFD) and angiotensin II (AngII) infusion. Mice developed HFpEF and comorbidities such as obesity, type 2 diabetes, and hypertension. MCC950 was added to HFD and groups were treated for four weeks until the study endpoint. MCC950 treatment resulted in lower plasma IL-18 levels (-47.3 %), illustrating target engagement. First, we observed that MCC950 treatment improved left ventricular function, demonstrated by enhanced global longitudinal strain (GLS, 3.9 %, P<0.01) and reverse peak longitudinal strain (RPLSR, +46.8 %, P<0.05). Second, MCC950 reduced cardiac hypertrophy (cardiomyocyte size -19.5 %, P<0.001) and fibrosis (-32.5 %, P<0.05), accompanied by lower expression of pro-fibrotic genes. Finally, MCC950 treatment reduced macrophage infiltration in left ventricular tissue and attenuated macrophage accumulation in visceral adipose tissue, even more as compared to caloric restriction. Overall, this suggests that NLRP3 inhibition could be a promising treatment for HFpEF patients with a pro-inflammatory profile, potentially improving heart function, systemic inflammation, and metabolic parameters.

Hypolipidemic and Cardioprotective Efficacy of Peltophorum pterocarpum Linn in Doxorubicin Induced Cardiotoxicity in Rats

Background: Cardiovascular disease (CVD) refers to a common group of illnesses affecting the heart and blood arteries. It encompasses heart valve problems, atherosclerosis, angina, cardiomyopathy, coronary artery disease (CAD), and infections of the heart which are considered the main causes of death. Modern medications have some success but they typically come with unfavorable side effects. Researchers are paying attention to herbal remedies because of their limited or no negative effects. This study was conducted to find out the hypolipidemic and cardioprotective potential of the ethanolic extract of Peltophorum pterocarpum (P. pterocarpum) Linn leaves in doxorubicin-induced cardiac damage in rats. Methods: The ethanolic extract of P. pterocarpum leaves was subjected to compound identification by GC-MS analysis. For in vivo analyses, the rats were divided into six groups. Cardiac damage was induced by doxorubicin at a dosage of 1.5 ml/kg b.wt. various dosages of extract (200 and 300 mg/kg b.wt.) were injected and propranolol (25 mg/kg b.wt.) is used as a standard drug. After the treatment of the extract, biochemical parameters were evaluated followed by in silico analysis. Result: The levels of cardiac marker and lysosomal enzymes significantly increased in toxin-treated rats, and the mitochondrial enzyme levels were significantly reduced. After treatment with P. pterocarpum leaf extract, the levels significantly (P less than 0.05) returned to normal. These results may prove the cardiac protective effect of the ethanolic extract of P. pterocarpum leaves in DOX-induced cardiotoxicity rats.

A temperature-ultrasound sensitive nanoparticle delivery system for exploring central neuroinflammation mechanism in stroke-heart syndrome

BackgroundCardiovascular events secondary to stroke–collectively classified as stroke-heart syndrome–greatly impair the patient’s prognosis, however its underlying mechanism has yet to be determined. To investigate the mechanism of central neuroinflammation and its effects on stroke-heart syndrome, a temperature-ultrasound responsive brain-targeted drug delivery system, DATS/MION-LPE, was synthesized to specifically study neuroinflammation in the mouse middle cerebral artery occlusion (MCAO) model.ResultsThe specific polymer of DATS/MION-LPE can close the nanoparticle pores at 37 °C, restricting drug release in the circulation. After the nanoparticles were targeted to brains, the polymer can be cleaved under external ultrasound irradiation, reopening the nanoparticle pores and allowing drug release, therefore directly managing the neuroinflammation. After a stroke, a significant cerebral inflammation occurred, with elevated IL-1β and pyrin domain-containing 3 (NLRP3) inflammasome. Accordingly, significantly increased histone deacetylase 6 (HDAC6) and decreased sirtuin 1 (SIRT1) were observed. An antagonistic relationship between HDAC6 and SIRT1 was found, which can jointly regulate the cerebral NLRP3 expression. The systemic IL-1β and ATP levels were increased after the stroke, accompanied by a significant heart injury including contractile dysfunction, elevated IL-1β levels, and oxidative stress. Meanwhile, neuroinflammation can trigger sympathetic nervous overexcitation with associated heart damage. DATS/MION-LPE can targetedly effect on ischemic brain, exhibiting cerebral and cardiac protective effects including downregulated cerebral NLRP3 and HDAC6 expressions, upregulated SIRT1 expressions in brain, reduced IL-1β and ATP in circulation, and alleviated cardiac impairment.ConclusionThis study introduced the key role of neuroinflammation in stroke-heart syndrome and first investigated the crucial HDAC6/SIRT1-NLRP3 circuit in this process. Heart injury secondary to stroke is mediated by neuroinflammation induced systemic inflammatory responses and sympathoexcitation. DATS/MION-LPE is a unique tool and effective therapeutic agent, which provides new insights into combinational heart and cardiac protection.Graphical

The Cardiac Protective Effects of Calcium Channel Blockers and Nitroglycerin in Cardiac Surgery: A Meta-analysis of Random Controlled Trials

The Cardiac Protective Effects of Calcium Channel Blockers and Nitroglycerin in Cardiac Surgery: A Meta-analysis of Random Controlled Trials

New insight for SS‑31 in treating diabetic cardiomyopathy: Activation of mitoGPX4 and alleviation of mitochondria‑dependent ferroptosis.

SS‑31 is a mitochondria‑targeting antioxidant that exhibits promising therapeutic potential for various diseases; however, its protective effect on diabetic cardiomyopathy (DCM) remains to be elucidated. At present, SS‑31 is considered not only to mitigate cardiolipin oxidative damage, but also to alleviate ferroptosis. The present study aimed to explore SS‑31 as a potential therapeutic strategy for improving DCM by alleviating mitochondria‑dependent ferroptosis. In vitro, H9C2 cells were exposed to 35 mM glucose for 24 h to induce high glucose damage, then were simultaneously treated with 10, 20 or 50 µM SS‑31. In addition, in vivo studies were conducted on diabeticC57BL/6J mice, which were induced to develop DCM over 4 weeks, followed by intraperitoneal injections with 2.5 mg/kg/day SS‑31 for a further 4 weeks. The elevation of serum lactate dehydrogenase and creatine kinase isoenzymes, the reduction of fractional shortening and ejection fraction, the rupture of myocardial fibers and the deposition of collagen indicated the establishment of the DCM mouse model. The results of the present study indicated that SS‑31 effectively alleviated these pathological changes and exhibited significant efficacy in ameliorating mitochondrial dysfunction, such as by promoting adenosine triphosphate generation, improving mitochondrial membrane potential and restoring the mitochondrial ultrastructure. Further experiments suggested that activation of the mitochondrial glutathione (mitoGSH)/mitochondrial glutathione peroxidase 4 (mitoGPX4) pathway and the elimination of mitochondrial ferrous ions may constitute the mechanisms by which SS‑31 treats DCM. Therefore, the present study revealed that mitochondria‑dependent ferroptosis could serve as a pathogenic mechanism of DCM and highlighted that the cardioprotective effects of SS‑31 against DCM involves activation of the mitoGSH/mitoGPX4 pathway. Due to the safety profile and cardiac protective effects of SS‑31, SS‑31 was considered a promising strategy for treating DCM.

Propolis (Bee Glue): A Promising Natural Feed Additive for Poultry and Rabbits – A Review

Abstract The concerns about the possible adverse effects of synthetic feed additives in livestock production world-wide has led producers to search for alternative natural feed additives. Propolis (bee glue) is a mixture of natural viscous substances that are collected by honeybees from plants. This natural product consists of about 200–300 compounds with high biological and pharmacological properties. Propolis induces an improvement in growth parameters, feed utilization, and meat quality. It also exerts antioxidant, anti-stress, antimicrobial, anti-inflammatory as well as immuno-modulatory and hepatic and cardiac protective effects. The presence of a huge amount of polyphenols such as flavonoids, phenolic acid esters, triterpenes, aromatic acids, diterpenic acids, and lignans are responsible for the biological properties of propolis. Therefore, propolis shows potential promising effects when applied in livestock and poultry production system. Accordingly, this review article is aimed to highlight the influences of propolis on the general health conditions of poultry and rabbits regarding the performance parameters and carcass characteristics, as well as the antioxidant, anti-stress, anti-microbial, anti-inflammatory, and the immuno-potentiation potentials.

Gastrodin Alleviates Angiotensin II-Induced Hypertension and Myocardial Apoptosis via Inhibition of the PRDX2/p53 Pathway In Vivo and In Vitro.

Gastrodin, a highly potent compound found in the traditional Chinese medicine Gastrodia elata Blume, exhibits significant antihypertensive properties. However, its role and the mechanism behind its protective effects on hypertensive cardiac conditions are not well understood. This study aims to investigate the cardiac protective effects and underlying mechanisms of gastrodin in angiotensin II (Ang II)-induced hypertensive models, both in vivo and in vitro. Treatment with gastrodin significantly decreased blood pressure and the heart weight/tibial length (HW/TL) ratio and attenuated cardiac dysfunction and pathological damage in Ang II-infused C57BL/6 mice. RNA sequencing analysis (RNA-seq) revealed 697 up-regulated and 714 down-regulated transcripts, along with 1105 signaling pathways, in Ang II-infused C57BL/6 mice following gastrodin treatment, compared to Ang II-induced hypertensive mice. Furthermore, the analyses of the top 30 Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway indicated significant enrichment in apoptosis and the peroxiredoxin 2 (PRDX2)/p53 pathway. Consistently, gastrodin treatment significantly reduced myocardial apoptosis in both the cardiac tissues of Ang II-induced hypertensive mice and Ang II-stimulated H9c2 cells. Additionally, gastrodin treatment significantly decreased the protein levels of PRDX2, p53, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 ratio in the cardiac tissues of Ang II-infused mice and H9c2 cells stimulated with Ang II. In conclusion, gastrodin treatment can mitigate hypertension-induced myocardial apoptosis in hypertensive mice by inhibiting the PRDX2/p53 pathway.

Xionggui Decoction alleviates heart failure in mice with myocardial infarction by inhibiting oxidative stress-induced cardiomyocyte apoptosis

To explore the protective effect of Xionggui Decoction against cardiac myopathy in a mouse model of heart failure following myocardial infarction (MI) and explore the underlying mechanism. We searched TCMSP, GeneCards, and CTD databases for the targets of active ingredients Xionggui Decoction and heart failure, and the intersecting targets were analyzed with GO and KEGG pathway enrichment analysis using DAVID database. In a mouse model of heart failure following acute MI induced by coronary artery ligation, the cardiac protective effects of 3 g/kg Xionggui Decoction were evaluated by assessing cardiac function, cardiac myopathy and ventricular remodeling of the mice using HE staining, Masson staining, RT-qPCR, and immunohistochemistry. We also tested the effect of Xionggui Decoction at 50 and 100 μg/mL on tertbutylhydrogen peroxide (TBHP)-induced apoptosis of H9C2 cells using CCK8 assay, detection kits for ROS, MDA, SOD, JC-1 and Hoechst 33342/PI staining. Network pharmacological analysis identified 62 potential targets of Xionggui Decoction for treatment of heart failure, and the core targets included PTGS2, ESR1, caspase-3, PPARG, HSP90AA1, BCL2, JUN, and GSK3B, which were involved in cell apoptosis and the AGE-RAGE, P53, PI3K-Akt, and VEGF signaling pathways. In the mouse models of heart failure, treatment with Xionggui Decoction significantly alleviated cardiac myopathy and ventricular remodeling, obviously improved heart function of the mice, lowered myocardial expressions of caspase-3 and BAX, and enhanced the expression of BCL2. In H9C2 cells, Xionggui Decoction significantly alleviated TBHP-induced cell apoptosis by inhibiting oxidative stress in the cells. Xionggui Decoction can alleviate myocardial injury and improve cardiac function in mice with heart failure following acute MI possibly by inhibiting cardiomyocyte apoptosis induced by oxidative stress.

Electroacupuncture pre-treatment exerts a protective effect on LPS-induced cardiomyopathy in mice through the delivery of miR-381 via exosomes

ObjectiveThis study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. Methods and resultsPre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. ConclusionsOur research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381.

IF1 Knockout Protects Against Doxorubicin-Induced Cardiac Dysfunction by Improving Cardiomyocyte Energetics

Doxorubicin (DOX), a member of the Anthracycline antibiotics class, has been used as a potent chemotherapy agent against solid tumors. However, its use is limited by its cardiotoxicity. It is well-documented that mitochondrial dysfunction is one of the main mechanisms of DOX-induced cardiotoxicity. ATP synthase inhibitory subunit 1 (ATPIF1, or IF1) is an endogenous inhibitor of mitochondrial ATP synthase. Recent studies indicate that IF1 may suppress mitochondrial respiration via inhibiting ATP synthase. Others and our previous studies demonstrated that IF1 inactivation exerts hepatic and cardiac protective effects. We hypothesize that the absence of IF1 protects the heart from DOX-induced cardiotoxicity by improving mitochondrial energy metabolism. We first investigate the impact of IF1 KO on mitochondrial respiration using the high-resolution respirometer (OROBOROS) on freshly isolated cardiac mitochondria from IF1 KO and WT mice. IF1 KO mitochondria did show substantially increased state 2, state 3, and state 4 respiration rates compared with those of WT. We then investigated if WT and IF1 KO mice respond differently to DOX treatment. WT and IF1 KO mice at the ages of 12-16 weeks either received DOX 3mg/kg/every other day or vehicle intraperitoneally for two weeks. In vivo, cardiac function was evaluated using the VEVO F2 Echocardiographic system (Visual Sonic) 4 and 6 weeks after initiation of DOX and vehicle administration. Compared with the vehicle-treated WT mice, left ventricular ejection fraction (LVEF) was substantially decreased in DOX-treated WT mice compared with vehicle-treated WT mice. In contrast, LVEF in DOX-IF1 KO mice was substantially less reduced compared with vehicle-treated IF1 KO mice. We next investigated if improving cellular energetics is the critical mechanism underlying the protective effects of IF1 KO. Mouse neonatal cardiomyocyte (NMCM) isolated from WT and IF1 KO mice were cultured and treated with 0.5 and 1mM Dox for 24 hours. Cellular energetics were measured with the Mito stress assay using the Seahorse Bioanalyzer (96Xpro, Agilent). Basal, maximal, and ATP production-linked oxygen consumption rates were markedly decreased in DOX-treated-NMCM but not in DOX-treated IF1 KO NMCM compared with Vehicle-treated NMCM. In summary, the above in vivo and in vitro investigations support that IF1 inactivation is protective against DOX cardiac toxicity, at least partly, via improving cellular energetics; therefore, inactivating IF1 may be a potential therapeutic target to prevent and mitigate DOX-induced cardiomyopathy in patients. This research was supported by project number 5R01HL160969 from the National Heart Lung and Blood Institute at the NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease.

Diabetic kidney disease is a frequent microvascular complication of diabetes and is currently the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Although the prevalence of other complications of diabetes is falling, the number of diabetic patients with end-stage kidney disease in need of kidney replacement therapy is rising. In addition, these patients have extremely high cardiovascular risk. It is more than evident that there is a high unmet treatment need in patients with diabetic kidney disease. Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist used for treating diabetic kidney disease. It has predominant anti-fibrotic and anti-inflammatory effects and exhibits several renal and cardiac protective effects. This review article summarizes the current knowledge and future prospects of finerenone in treating patients with kidney disease.

Remimazolam attenuates myocardial ischemia-reperfusion injury by inhibiting the NF-ĸB pathway of macrophage inflammation

BackgroundInflammation is a major contributing factor in myocardial ischemia/reperfusion (I/R) injury, and targeting macrophage inflammation is an effective strategy for myocardial I/R therapy. Though remimazolam is approved for sedation, induction, and the maintenance of general anesthesia in cardiac surgery, its effect on cardiac function during the perioperative period has not been reported. Therefore, this research aimed to explore the impact of remimazolam on inflammation during myocardial ischemia/reperfusion (I/R) injury. MethodsAn in vivo myocardial I/R mice model and an in vitro macrophage inflammation model were used to confirm remimazolam's cardiac protective effect. In vivo, we used echocardiography, hematoxylin and eosin (HE), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining to determine remimazolam's therapeutic effects on myocardial I/R injury and inflammation. In vitro, we employed enzyme-linked immunosorbent assay (ELISA), Western blot, Real-time Quantitative PCR (qPCR), flow cytometry, and immunofluorescence staining to assess inflammatory responses, especially remimazolam's effects on macrophage polarization after I/R. Furthermore, molecular docking was used to identify its potential binding targets on the inflammatory pathway to explore the mechanism of remimazolam. ResultsRemimazolam exhibited significant anti-myocardial I/R injury activity by inhibiting macrophage-mediated inflammation to reduce myocardial infarction, enhancing cardiac function. In addition, macrophage depletion counteracted improved cardiac function by remimazolam treatment. Mechanistically, the activated NF-ĸB signaling pathway and phosphorylation of p50 and p65 were repressed for anti-inflammatory effect. Consistently, two binding sites on p50 and p65 were identified by molecular docking to affect their phosphorylation of the Ser, Arg, Asp, and His residues, thus regulating NF-κB pathway activity. ConclusionOur results unveil the therapeutic potential of remimazolam against myocardial I/R injury by inhibiting macrophages polarizing into the M1 type, alleviating inflammation.

Shenxiang Suhe pill improves cardiac function through modulating gut microbiota and serum metabolites in rats after acute myocardial infarction

Context Shenxiang Suhe pill (SXSH), a traditional Chinese medicine, is clinically effective against coronary heart disease, but the mechanism of cardiac-protective function is unclear. Objective We investigated the cardiac-protective mechanism of SXSH via modulating gut microbiota and metabolite profiles. Materials and methods Sprague-Dawley (SD) male rats were randomly divided into 6 groups (n = 8): Sham, Model, SXSH (Low, 0.063 g/kg; Medium, 0.126 g/kg; High, 0.252 g/kg), and Ato (atorvastatin, 20 mg/kg). Besides the Sham group, rats were modelled with acute myocardial infarction (AMI) by ligating the anterior descending branch of the left coronary artery (LAD). After 3, 7, 14 days’ administration, ultrasound, H&E staining, serum enzymic assay, 16S rRNA sequencing were conducted to investigate the SXSH efficacy. Afterwards, five groups of rats: Sham, Model, Model-ABX (AMI with antibiotics-feeding), SXSH (0.126 g/kg), SXSH-ABX were administrated for 14 days to evaluate the gut microbiota-dependent SXSH efficacy, and serum untargeted metabolomics test was performed. Results 0.126 g/kg of SXSH intervention for 14 days increased ejection fraction (EF, 78.22%), fractional shortening (FS, 109.07%), and aortic valve flow velocities (AV, 21.62%), reduced lesion area, and decreased serum LDH (8.49%) and CK-MB (10.79%). Meanwhile, SXSH upregulated the abundance of Muribaculaceae (199.71%), Allobaculum (1744.09%), and downregulated Lactobacillus (65.51%). The cardiac-protective effect of SXSH was disrupted by antibiotics administration. SXSH altered serum metabolites levels, such as downregulation of 2-n-tetrahydrothiophenecarboxylic acid (THTC, 1.73%), and lysophosphatidylcholine (lysoPC, 4.61%). Discussion and conclusion The cardiac-protective effect and suggested mechanism of SXSH could provide a theoretical basis for expanding its application in clinic.

Treatment of ischemic heart failure through ultrasound-targeted microbubble destruction and it's mechanism

Abstract Background The cavitation effect mediated by ultrasonic-targeted microbubble destruction (UTMD) can regulate the microenvironment and circulation of ischemic myocardium. The UTMD cavitation effect can rapidly enhance blood perfusion and improve cardiac function in patients with ischemic heart failure. However, the internal mechanism of this treatment has yet to be reported. Objective The objective of this study was to explore the underlying mechanism of UTMD-mediated cavitation effect to rapidly improve cardiac function in rats with ischemic heart failure. Methods In the first part of the study, the ischemic heart failure model was induced by ligation of the left anterior descending branch coronary in Sprague-Dawley rats, the rats were randomly divided into 7 groups: sham group, HF group, HF+MB(microbubble) group, HF+US(ultrasound) group, HF+UTMD group, HF+UTMD+LY294002(PI3K inhibitor) group, and HF+LY294002 group. Serum BNP level and echocardiographic parameters were measured to evaluate cardiac function. Thereafter, SD rats were treated with UTMD by specific ultrasonic parameters and microbubble concentration, cardiac function should be reassessed after treatment. Finally, the myocardial tissues were extracted for Western Blot and immunohistochemical analysis to detect the protein expression of the PI3K/Akt/eNOS signaling pathway, and the contents of serum nitric oxide(NO) and myocardial ATP were detected by Elisa. Results The application of UTMD resulted in significant improvements in ejection fraction (EF) and fractional shortening (FS) in rats with ischemic heart failure, as compared to the HF group (EF: 37.16 ± 1.21% vs. HF+UTMD: 46.31 ± 3.00%, P=0.0057; FS: 18.53 ± 0.58% vs. HF+UTMD: 24.05 ± 1.84%, P=0.0089). Additionally, UTMD treatment led to the activation of the PI3K/Akt/eNOS signaling pathway (HF vs. HF+UTMD, P &amp;lt; 0.01), and promoted the production of NO and ATP (HF vs. HF+UTMD, both, P&amp;lt; 0.05). However, when a PI3K inhibitor was used, the cardiac protective effects of UTMD treatment were largely eliminated. EF and FS deteriorated significantly (EF: HF+UTMD+LY294002: 42.84±2.88% vs. HF+LY294002: 32.73±3.05%, P&amp;lt;0.0001; FS: HF+UTMD+LY294002: 21.94±1.69% vs. HF+LY294002: 16.36±1.76%, P&amp;lt;0.0001), and the production of NO and ATP decreased significantly (HF+UTMD+LY294002 vs. HF+LY294002, both, P&amp;lt; 0.05). Conclusion The UTMD-mediated cavitation effect can rapidly improve the cardiac function of ischemic heart failure rats by activating PI3K/Akt/eNOS signaling pathway and promoting the release of NO and ATP.

The effect of sglt-2 inhibitor dapagliflozin on adropin serum levels in patients with chronic heart failure and concomitant type 2 diabetes mellitus

Abstract Background adropin plays a protective role in cardiac remodeling through supporting energy metabolism and water homeostasis and suppressing inflammation. Low circulating levels of adropin were positively associated with the risk of cardiovascular diseases and type 2 diabetes mellitus (T2DM). We hypothesized that sodium–glucose linked transporter 2 (SGLT2) inhibitor dapagliflosin might represent cardiac protective effects in T2DM patients with known chronic heart failure (HF) through the modulation of adropin levels. Methods The study was an open-label, multicenter non-randomized cohort investigation. Patients of both sexes were included from October 2020 to July 2022 who were aged ≥18 years and had established T2DM with HbAc1 &amp;lt;6.9%, hemodynamically stable HF (I-III NYNA functional classes), and written consent to participate in the study. According to these criteria, we prospectively enrolled 417 patients with T2DM and HF. The eligible patients were treated with the recommended guided HF therapy according to their HF phenotypes, including the consumption of SGLT2 inhibitor dapagliflozin at a dose of 10 mg OD orally, along with standard therapy of HF. Anthropometry, clinical data, echocardiography / Doppler examinations, and measurements of biomarkers were performed at the baseline and over a 6-month interval of SGLT2 inhibitor administration. Results Over a 6-month period after the initial prescription of SGLT2 inhibitor dapagliflozin, the levels of adropin in the entire group demonstrated a significant increase of up to 26.6% (from 2.37 [25–75% IQR = 1.91–2.75] ng/mL to 3.00 [25−75% IQR = 2.68–3.36] ng/mL, p = 0.042). In the female subgroup, the increase in the circulating levels of adropin was sufficiently higher (Δ% = 35.6%, from 2.69 [25–75% IQR = 2.31–2.99] ng/mL to 3.65 [25–75% IQR = 3.40–3.89] ng/mL, p = 0.010)when compared with those of the male subgroup (Δ% = 22.7%, from 2.11 [25–75% IQR = 1.90–2.37] ng/mL to 2.60 [25–75% IQR = 2.07–3.21] ng/mL, p = 0.161). A multivariate linear regression analysis of the entire group showed that the relative changes (Δ) in the left ventricular (LV) ejection fraction (LVEF), left atrial volume index (LAVI), and E/e` were significantly associated with increased adropin levels. In the female subgroup, but not in the male subgroup, ΔLVEF (p = 0.046), ΔLAVI (p = 0.001), and ΔE/e` (p = 0.001) were independent predictive values for adropin changes. Conclusion the levels of adropin seem to be a predictor for the favorable modification of hemodynamic performances during SGLT2 inhibition, independent of N-terminal brain natriuretic pro-peptide levels.

Abstract 16488: Sestrin2 Protects Against Long-Term Cardiac Injury and Remodeling by Modulating mTORC1 Activation in Myocardial Ischemia/Reperfusion

Introduction: Myocardial ischemia/reperfusion (I/R) injury can lead to long-term cardiac dysfunction and heart failure with reduced ejection fraction (HFrEF) in aged hearts. However, young hearts may exhibit some resistance to this process and retain better cardiac function. Our previous studies have identified a novel protein called Sestrin2 (Sesn2), which is downregulated in aged hearts. Hypothesis: Sesn2 may protect hearts from progressing to HFrEF following myocardial I/R. Methods: We induced myocardial I/R injury by ligation/release of the left anterior descending coronary arteries (LAD) in both C57BL/6J mice and mice with cardiac-specific Sesn2 knockout (Sesn2 cKO ). Cardiac function was assessed, and samples were collected at baseline, one day post I/R, seven days post I/R, and 28 days post I/R. Results: In wild-type (WT) hearts (12-18 weeks), cardiac function showed a slight decrease 28 days post I/R (IR28D), but the ejection fraction (EF) remained above 50%. However, Sesn2 cKO mice exhibited a significant reduction in cardiac function at IR28D, with an about 27.5% decrease in EF compared to WT hearts. We also observed a significant increase in volume at diastole in Sesn2 cKO mice at IR28D compared to their baseline and corresponding WT. Furthermore, when comparing mitochondrial respiration in the area at risk (AAR) of the left ventricles between the two groups, we found a significant decrease in oxygen consumption rate (OCR) and a significant increase in H 2 O 2 production in Sesn2 cKO hearts. Additionally, the mammalian target of rapamycin complex 1 (mTORC1) was significantly upregulated in Sesn2 cKO mice compared to WT hearts. Conclusions: Sesn2 exerts a cardiac protective effect by downregulating mTORC1 activation, thereby reducing long-term cardiac injury following I/R, attenuating cardiac remodeling, and improving mitochondrial respiration in the AAR of the heart.

Chia (Salvia Hispanica): An Overview of Its Botany, Uses, Reproductive, Biology, Pharmacological Properties and Industrial Potentials

The consumption of chia seed (Salvia hispanica L.) has increased in recent years due to its high content of omega-3 and omega-6 fatty acids and dietary fibre. This seed also has a high concentration of proteins and essential amino acids, becoming a promising source of bioactive compounds such as chlorogenic acid, caffeic acid, myricetin, quercetin and kaempferol with the major phenolic acid being rosmarinic acide. Owing to the rich nutritional profile, chia seeds provide numerous health benefits such as cardiac and hepatic protective effects, anti-aging and anti-carcinogenic properties. The high amounts of dietary fibres present in the seeds also confer benefits by preserving good glycemic control thus helping in controlling diabetes mellitus. In addition to the food industry for the development of various baked products, production of biodegradable edible films, use as emulsifiers and stabilizers among other uses. In this article we have focused on drafting a technical description of the chia.

Oridonin ameliorates doxorubicin induced-cardiotoxicity via the E2F1/Sirt6/PGC1α pathway in mice

Doxorubicin induced cardiotoxicity (DIC) arises from mitochondrial dysfunction and oxidative stress. Oridonin (Ori), a natural tetracycline diterpenoid, has shown cardiac protective effect; however, its role in DIC remains unclear. This study investigates the protective effect of Ori against DIC and elucidates its underlying molecular mechanisms. The results demonstrate that Ori significantly alleviated DIC by improving myocardial structure, reducing the proportion of apoptotic cells, and alleviating the myocardial oxidative damage and mitochondrial dysfunction both in vivo and in vitro. Doxorubicin significantly decreased Sirt6 and PGC1α levels in cardiac tissues, which was reversed by Ori. Furthermore, Sirt6 overexpression significantly improved myocardial structure and reduced the proportion of apoptotic cells by reducing oxidative stress and improving mitochondrial function. The protective effect of Ori is neutralized by the Sirt6 inhibitor OSS_128167, evidenced by downregulated mRNA and protein expression of PGC1α. The transcription factor E2F1 was upregulated by doxorubicin, leading to decreased Sirt6 expression-an effect mitigated by Ori. Molecular docking simulations indicate direct binding between Ori and specific amino acid residues on E2F1 through hydroxyl bonds. These findings uncover a novel mechanism whereby Ori attenuates DIC by modulating the E2F1/Sirt6/PGC1α pathway.