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Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field. [Display omitted] • Ferroptosis is crucial in numerous cardiovascular diseases (CVDs). • Ferroptosis interacts with other cell death modes in CVDs. • Modulating iron, lipid metabolism, and antioxidants can inhibit ferroptosis in CVDs. • Ferroptosis inhibitor development brings new hope for CVD treatment. • Ferroptosis mechanisms in various CVDs must be further revealed. [ABSTRACT FROM AUTHOR]

Heart diseases are the primary cause of mortality and morbidity worldwide which inflict a heavy social and economic burden. Among heart diseases, most deaths are due to myocardial infarction (MI) or heart attack, which occurs when a decrement in blood flow to the heart causes injury to cardiac tissue. Despite several available diagnostic, therapeutic, and prognostic approaches, heart disease remains a significant concern. Exosomes are a kind of small extracellular vesicles released by different types of cells that play a part in intercellular communication by transferring bioactive molecules important in regenerative medicine. Many studies have reported the diagnostic, therapeutic, and prognostic role of exosomes in various heart diseases. Herein, we reviewed the roles of exosomes as new emerging agents in various types of heart diseases, including ischemic heart disease, cardiomyopathy, arrhythmia, and valvular disease, focusing on pathogenesis, therapeutic, diagnostic, and prognostic roles in different areas. We have also mentioned different routes of exosome delivery to target tissues, the effects of preconditioning and modification on exosome's capability, exosome production in compliance with good manufacturing practice (GMP), and their ongoing clinical applications in various medical contexts to shed light on possible clinical translation. [Display omitted] • Exosomes aid cardiac regeneration, beyond their intercellular communication function. • Exo-mi-RNAs induce cardiac regeneration by angiogenesis, anti-inflammation, and anti-apoptosis. • Exosomes can be injected intracardially, intraperitoneally, intravenously, or subcutaneously. • Ongoing clinical trials on exosomes in heart disease explore their biomarker and regenerative potential." [ABSTRACT FROM AUTHOR]

Angiogenesis has been considered a pivotal strategy for treating ischemic heart disease. One possible approach, the Shexiang Baoxin Pill (MUSKARDIA), has been noted to promote angiogenesis, but its underlying mechanism is still largely unknown. We aimed to determine the effects of MUSKARDIA on acute myocardial infarction (AMI), as well as the underlying mechanistic bases. AMI was induced in rats, using left anterior descending coronary arterial occlusion, and either 6 (low) or 12 (high-dose) mg/kg/day of MUSKARDIA was administered for 56 days. We found that MUSKARDIA improved cardiac function and counteracted against adverse remodeling among AMI rats, which most likely is due to it promoting angiogenesis. Transcriptome analysis by RNA-sequencing found that MUSKARDIA up-regulated cardiac pro-angiogenic genes, particularly growth differentiation factor 15 (GDF15), which was confirmed by RT-qPCR. This up-regulation was also correlated with elevated serum GDF15 levels. In vitro analyses with human umbilical vein endothelial cells found that increased GDF15, stimulated by MUSKARDIA, resulted in enhanced cell migration, proliferation, and tubular formation, all of which were reversed after GDF15 knockdown using a lentiviral vector. Gene Ontology, as well as Kyoto Genes and Genomes enrichment analyses identified calcium signaling pathway as a major contributor to these outcomes, which was verified by Western blot and Cal-590 AM loading showing that transient receptor potential cation channel subfamily V member 4 protein (TRPV4) and intracellular Ca2+ levels increased in accordance with MUSKARDIA-induced GDF15 up-regulation, and decreased with GDF15 knock-down. Therefore, MUSKARDIA may exert its cardioprotective effects via stimulating the GDF15/TRPV4/calcium signaling/angiogenesis axis. [Display omitted] • MUSKARDIA exerts cardioprotective effects in acute myocardial infarction (AMI). • The underlying mechanism is the promotion of peri-infarct angiogenesis by MUSKARDIA. • MUSKARDIA up-regulates pro-angiogenic GDF15 and calcium ion channel TRPV4. • GDF15/TRPV4/calcium signal/angiogenesis axis underlies MUSKARDIA alleviating AMI. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is the leading cause of deaths worldwide, triggering widespread and irreversible damage to the heart. Currently, there are no drugs that can reverse ischemic damage to the myocardium and hence, finding novel therapeutic agents that can limit the extent of myocardial damage following MI is crucial. Liensinine (LSN) is a naturally derived bisbenzylisoquinoline alkaloid that is known to exhibit numerous antioxidative and cardiovascular beneficial effects. However, the role of LSN in MI-induced injury and its underlying mechanisms remain unexplored. Our study aims to evaluate the cardioprotective effects of LSN following MI and its underlying molecular mechanisms. We constructed murine models of MI in order to examine the potential cardioprotective effects and mechanisms of LSN in protecting against myocardial ischemic damage both in vivo and in vitro. Administration with LSN strongly protected against cardiac injuries following MI by decreasing the extent of ischemic damage and improving cardiac function. Additionally, LSN was found to be a potent inhibitor of Wnt/β‑catenin signaling pathway. Hence, the beneficial effects of LSN in preventing oxidative and DNA damage following ischemia was due to its ability to inhibit aberrant activation of Wnt/β‑catenin signaling. Our findings reveal for the first time a novel cardioprotective role of LSN during myocardial infarction and most notably, its ability to protect cardiomyocytes against oxidative stress-induced damage via inhibiting Wnt/β-catenin signaling. Our study therefore suggests new therapeutic potential of LSN or plants that contain the natural alkaloid LSN in ischemic heart diseases. [Display omitted] • Liensinine is a natural alkaloid that exhibits strong cardioprotective effects. • Liensinine robustly protects against ischemic injury after myocardial infarction. • Liensinine attenuates ischemia-induced oxidative and DNA damage. • Cardioprotective effects of Liensinine is via inhibiting Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Congestive heart failure (CHF) is a complicated pathophysiological syndrome, leading cause of hospitalization as well as mortalities in developed countries wherein an irregular function of the heart leads to the insufficient blood supply to the body organs. It is an accumulative slackening of various complications including myocardial infarction (MI), coronary heart disease (CAD), hypertension, valvular heart disease (VHD) and cardiomyopathy; its hallmarks include hypertrophy, increased interstitial fibrosis and loss of myocytes. The etiology of CHF is very complex and despite the rapid advancement in pharmacological and device-based interventional therapies still, a single therapy may not be sufficient to meet the demand for coping with the diseases. Total artificial hearts (TAH) and ventricular assist devices (VADs) have been widely used clinically to assist patients with severe HF. Unfortunately, direct contact between the patient’s blood and device leads to thromboembolic events, and then coagulatory factors, as well as, infection contribute significantly to complicate the situation. There is no effective treatment of HF except cardiac transplantation, however, genetic variations, tissue mismatch; differences in certain immune response and socioeconomic crisis are an important concern with cardiac transplantation suggesting an alternate bridge to transplant (BTT) or destination therapies (DT). For these reasons, researchers have turned to mechanically driven compression devices, ventricular restraint devices (VRD) and heart patches. The ASD is a combination of all operational patches and cardiac support devices (CSD) by delivering biological agents and can restrain or compress the heart. Present study summarizes the accessible peer-reviewed literature focusing on the mechanism of Direct Cardiac Compression (DCC) devices, VRD and patches and their acquaintance to optimize the therapeutic efficacy in a synergistic way. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is one of the most common ischemic heart diseases. However, lack of sufficient drug concentrations in the ischemic heart may led to treatment failure. It is urgent for researchers to engineer novel drug delivery systems to enhance the targeted delivery of cardioprotective agents. The aim of the present study was to investigate the anti-AMI ability of calycosin (CAL) and tanshinone (TAN) co-loaded mitochondria targeted lipid-polymer hybrid nano-system. CAL and TAN combined lipid-polymer hybrid nano-systems were prepared and MTP-131 was conjugated with PEG and modified onto the nanoparticles to achieve MTP-CAL/TAN NS. The physicochemical properties of nano-systems were characterized, the AMI therapy ability of the systems was investigated in AMI rats' model. The size of MTP-CAL/TAN NS was 168.7 ± 5.1 nm, with a surface charge of − 21.3 ± 2.3 mV. The area under the curve (AUC) and blood circulation half-life (T 1/2) of MTP-CAL/TAN NS was 178.86 ± 6.62 μg·min/mL and 0.47 h, respectively. MTP-CAL/TAN NS exhibited the most significant infarct size reduction effect of 23.9 %. MTP-CAL/TAN NS exhibited the highest heart accumulation and best infarct size reduction effect, which could be used as a promising system for efficient treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes mellitus (T2DM) face a high risk of developing cardiovascular diseases. However, traditional hypoglycemic drugs have limited effects on macrovascular complications of the disease. Clinical trials have confirmed that glucagon-like peptide-1 receptor agonists (GLP-1RAs), in addition to their capability of controlling blood glucose, can also decrease the risk of cardiovascular events in T2DM. The protective influence of GLP-1RAs on coronary heart disease and heart failure has been proven in recent clinical studies. Therefore, the international guidelines recommend GLP-1 RAs as the first-line therapy for patients with T2DM having cardiovascular disease. Notwithstanding the widespread clinical application of GLP-1RAs, the underlying mechanisms through which GLP-1RAs exert cardiovascular benefits in patients with DM remain unclear. In this review, we systematically summarize the mechanisms of action of GLP-1RAs responsible for producing favorable effects on the cardiovascular system, beyond their capability of blood glucose regulation. GLP-1RA-mediated cardiovascular protection is manifested through multiple mechanisms, including oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and vascular/cardiac remodeling. The understanding of these mechanisms will facilitate the development of new and promising therapeutic modalities for T2DM. Furthermore, we have identified several promising targets for future research in this area. • GLP-1RA is a new type of hypoglycemic drug which potently lowers blood glucose and body weight. • Clinical evidences demonstrated GLP-1RAs reduced the risk of MACE, non-fatal myocardial infarction and heart failure. • GLP-1RAs exert anti-oxidative, anti-inflammatory, anti-apoptotic, and anti-remodeling effects on cardiac and vascular cells. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among all types of diseases in the world, affecting many millions of individuals every year. CVD includes hypertension, atherosclerosis, pulmonary hypertension, heart failure, cardiomyopathy, coronary heart disease, etc., which are involved in complex etiology, pathogenesis and many risk factors. Modern pharmacological studies have revealed that Epimedium possesses a variety of beneficial effects in regulating cardiovascular inflammation and other biological activities, which provides a therapeutic value for the prevention and treatment of these cardiovascular diseases. In this review, we discuss the cardiovascular protective effects of icariin, an active component from Epimedium, and its metabolites. We summarize a range of studies showing that the modes of action of icariin on CVD relate to its inhibition of myocardial apoptosis and prevention of inflammation on endothelial cell injury, emphasizing the multiple effects of icariin and its metabolites in the repair of common heart failure and myocardial infarction, as well as the formation of neointima. In particular, an emphasis is placed on the discussion of the action mechanism of icariin in combination with new advances in the understanding of the pathology of CVD with potential application of icariin in the treatment of this human disorder. [ABSTRACT FROM AUTHOR]

Aspirin (ASA) is widely used as an antiplatelet therapeutic drug in secondary prevention. Last years brought many reports on ASA resistance or high on-treatment platelet reactivity (HTPR) to aspirin.This study is a post-hoc prospective analysis with 30 patients evaluated during follow up on average of 6.3 years after hospitalization from myocardial infarction. The examined population was divided into two subgroups according to the response to ASA. In order to estimate the function of blood platelets and their responsiveness to acetylsalicylic acid therapy, ASPI-test was used. The measurements were performed by the method of whole blood impedance aggregometry. During long-term follow up significantly higher percentage of high platelet reactivity was observed, compared with previous visits (p = 0.00001). Considering clinical endpoints of the research that were connected with coronary disease, no differences were obtained.The frequency of HTPR to aspirin in this study was higher than data reported in literature among subjects with CV diseases. In long-term observation the highest percentage of ASA non-responders was reported (58.6%). HTPR to aspirin did not affect the presence of the clinical endpoints for the study. [Display omitted] • The frequency of ASA resistance was higher than data reported in literature among subjects with cardiovascular diseases. • In long-term observation the highest percentage of ASA non-responders was reported. • The presence of ASA resistance did not affect the presence of the clinical endpoints for the study. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the mechanism and effects of " Danggui–kushen " herb pair (DKHP) better than single drug in ischemic heart disease (IHD). IHD model was established by left anterior descending branch of coronary artery in rats. Rats were randomized into six groups and oral administration for 7 days: control, model, Danshen dripping pills (DS) (5.103 g/kg), Danggui (DG) (2.7 g/kg), Kushen (KS) (2.7 g/kg) and DKHP (2.7 g/kg). Electrocardiogram (ECG), myocardial infarction and damage assessment, histological inspection analysis, and various biochemical indexes of myocardial tissue were measured to evaluate the myocardial damage and the protective effects of drugs. The inflammatory levels were identified by HE staining and serum cytokine, and the expression of hypoxia-inducible factor 1α (HIF-1α), inhibitor kappa B kinaseβ (IKKβ) and nuclear transcription factor kappa B (NF-κB) were measured by immunohistochemistry. The results suggested that: compared with the control group, model group showed significantly myocardial tissue abnormalities, and increased levels of inflammatory cytokine. Treatment with drugs inhibited the increase of α-hydroxybutyrate dehydrogenase (α-HBDH), creatine kinase (CK), creatinekinase isoenzyme (CK-MB), interleukin 1 (IL-1) and interleukin 6 (IL-6). The results of immunohistochemical showed that drugs-treatment inhibited the expression of IKKβ and the P-p65, increased the expression of HIF-1α, which demonstrated that the anti-inflammatory effects of DKHP was achieved by suppressing of NF-κB signaling. These observations indicated that DKHP can ameliorate myocardial injury better than single. And these are related to the inhibition of NF-κB and actives HIF-1α signaling. [Display omitted] • Angelica - Sophora flavescens is a traditional Chinese medicine pair. The combination of the two drugs improved the state of myocardial ischemia. • Inflammation and hypoxia are the key pathologic states of ischemic heart disease. • HIF-1 affects inflammation, cancer and the cardiovascular system. • Angelica-Sophora flavescens can control inflammation and affect HIF-1 by regulating NF-κB. [ABSTRACT FROM AUTHOR]

Alterations in xanthine oxidase activity are known to be pathologically influential on coronary artery disease (CAD), but the association between purine-related blood metabolites and CAD has only been partially elucidated. We performed global metabolomics profiling and network analysis on blood samples from the Wonju and Pyeongchang (WP) cohort study (n = 2055) to elucidate the importance of purine related metabolites associated with potential CAD risk. Then, 5 selected serum metabolites were quantified from the WP cohort, Shinchon cohort (n = 259), and Shinchon case control (n = 424) groups to develop machine learning models for 10-year risk prediction, relapse within 10 years and diagnosis of the disease via 100 repeated 5-fold cross-validations of logistic models. The combination of purine metabolite levels or only xanthine levels in blood could be applied for machine learning model development for major adverse cardiac and cerebrovascular event (MACCE, cerebrovascular death, nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, and stroke) risk prediction, relapse of MACCEs among patients with myocardial infarction history and diagnosis of stable CAD. In particular, our research provided initial evidence that blood xanthine and uric acid levels play different roles in the development of machine learning models for primary/secondary prevention or diagnosis of CAD. In this research, we determined that purine-related metabolites in blood are applicable to machine learning model development for CAD risk prediction and diagnosis. Also, our work advances current CAD biomarker discovery strategies mainly relying on clinical features; emphasizes the differential biomarkers in first/secondary prevention or diagnosis studies. • Purine-related metabolites in blood are applicable to machine learning model for CAD risk prediction and diagnosis. • Xanthine and uric acid levels play different roles in the development of machine learning models for prevention or diagnosis of CAD. • There are possible changes in the role of metabolic features in machine learning model developments for prevention or diagnosis of diseases. [ABSTRACT FROM AUTHOR]

• Dexmedetomidine induces protection by decreasing myocardial infarction and apoptosis of H9C2 cells. • miR-146a-3p is downregulated after myocardial ischemia/reperfusion and H9C2 anoxia/reoxygenation. • Involve of miR-146a-3p/IRAK1/TRAF6/NF-κB axis in dexmedetomidine-induced cardioprotection. Myocardial ischemia/reperfusion (I/R) injury is a common cause of mortality. Cardiac miR-146a is emerging as a potent regulator of myocardial function. Dexmedetomidine preconditioning provides cardioprotective effects, of which mechanisms related to miR-146a-3p are unclear. A myocardial I/R model in rats and a cellular anoxia/reoxygenation (A/R) model in H9C2 cells were established and preconditioned with dexmedetomidine or not. H9C2 cells were transfected with mimics, inhibitor, or negative controls of miR-146a-3p, and siRNAs of IRAK1 or TRAF6. Relative expressions of miR-146a-3p were determined by quantitative real-time polymerase chain reaction. The apoptosis rates and reactive oxygen species (ROS) levels in H9C2 cells were examined by flow cytometry. Protein expressions of IRAK1, TRAF6, cleaved Caspase-3, BAX, BCL-2, NF-κB p65, phosphorylated NF-κB p65 (p-NF-κB p65), IκBα, and phosphorylated IκBα (p-IκBα) in H9C2 cells were detected by Western blot. Dexmedetomidine decreased myocardial infarction size and apoptosis rates of H9C2 cells. Dexmedetomidine upregulated expression of miR-146a-3p. Dexmedetomidine significantly decreased protein expressions of IRAK1, TRAF6, cleaved Caspase-3, BAX, and NF-κB p65, but increased expressions of BCL-2 in H9C2 cells. miR-146a-3p overexpression strengthened the anti-apoptotic effect induced by dexmedetomidine in H9C2 cells via decreasing protein levels of IRAK1, TRAF6, cleaved Caspase-3, BAX, NF-κB p65, p-NF-κB p65, and p-IκBα and increasing protein level of BCL-2. Downregulation of miR-146a-3p reversed the changes in these proteins in H9C2 cells. Expressions of NF-κB p65 and p-NF-κB p65 were further decreased following knockdown of IRAK1 or TRAF6. ROS emission was significantly increased after A/R, while significantly decreased following dexmedetomidine preconditioning in H9C2 cells transfected with siIRAK1 or siTRAF6. miR-146a-3p targeting IRAK1 and TRAF6 through inhibition of NF-κB signaling pathway and ROS emission is involved in cardioprotection induced by dexmedetomidine pretreatment. [ABSTRACT FROM AUTHOR]

• Both total saponins from Panacis majoris Rhizoma (TSPJ) and the degradation products of TSPJ (DTSPJ) were prepared. • The main constituents of TSPJ and DTSPJ were analyzed and the possible mechanisms were also investigated. • The protection of DTSPJ against myocardial ischemia-reperfusion injury was a little stronger than those of TSPJ. • DTSPJ represents a promising drug candidate for treating ischemic heart disease. Panacis majoris Rhizoma, which is a member of herbal medicine, is known for many years to remove blood stasis, promote blood circulation, and enrich the blood. The active ingredients of this plant are mainly attributed to saponins. The total saponins from Panacis majoris Rhizoma (TSPJ), and the degradation products of TSPJ (DTSPJ), were designed in this study to compare the protective effects on myocardial ischemia-reperfusion injury, and the aim of this approach is to discover more effective agents for the treatment of ischemic heart diseases. We analyzed the main constituents of TSPJ and DTSPJ, aiming to make clear which saponins played important roles in this protective effect, and also investigated the possible mechanisms. DTSPJ was prepared by the method of alkaline hydrolysis. High performance liquid chromatography (HPLC) were used to analyze the main chemical constituents of TSPJ and DTSPJ, which were isolated by chromatographic techniques and identified by comparison with the Nuclear Magnetic Resonance (NMR) data in reported literature. Male Wistar rats were randomized to sham-operated group, ischemia-reperfusion group, three TSPJ (50, 100 and 200 mg/kg) groups, three DTSPJ (50, 100 and 200 mg/kg) groups, and isosorbide dinitrate tablet (5.0 mg/kg) group. The rats in all groups were intragastrically administrated once per day for three successive days. The establishment of the model of myocardial ischemia-reperfusion injury was used the following method: firstly, the left coronary artery of experimental rat was ligated for 30 min and then reperfused for 120 min. Then the myocardial infarct size, hemorheological and biochemical parameters, whole blood viscosity, plasma viscosity, platelet adhesion rate, platelet aggregation and histopathology changes were assessed. Five C 3 ,C 28 -bidesmosidic oleanane-type saponins and ginsenoside Rd were the main constituents of TSPJ, and their total content in TSPJ was 79.2 %. The main constituents of DTSPJ were five C 3 -monodesmosidic oleanane-type saponins and ginsenoside Rd, and their total content in DTSPJ was 72.6 %. The HPLC analysis revealed that the five C 3 ,C 28 -bidesmosidic oleanane-type saponins in TSPJ were completely turned into five C 3 -monodesmosidic oleanane-type saponins in DTSPJ through the method of alkaline hydrolysis, but ginsenoside Rd remained unchanged. Both TSPJ and DTSPJ could significantly reduced myocardial infarct size, and improved heart function, and lowered the activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase isoenzymes (CK-MB), and malonyldialdehyde (MDA) content, as well as the levels of whole blood viscosity, plasma viscosity, platelet adhesion rate, and platelet aggregation; on the contrary, both the level of glutathione peroxidase (GSH-Px) and the activity of superoxide dismutase (SOD) were notablely increased. The results of histopathological examination further supported the cardioprotective effects of TSPJ and DTSPJ. Both TSPJ and DTSPJ can guard cardiomyocytes against myocardial ischemia-reperfusion injury. The underlying mechanisms may be closely related to its enhancing anti-oxidative properties, modifying blood viscosity, and inhibiting platelet aggregation and platelet adhesion. As a whole, the protection of DTSPJ against myocardial ischemia-reperfusion injury was a little stronger than those of TSPJ. The results display the prospect of DTSPJ as a drug candidate for treating ischemic heart disease. [ABSTRACT FROM AUTHOR]

• Sevoflurane and propofol have previously been implicated in myocardial protection. • In a non-conditioning protocol only sevoflurane reduced myocardial ischemic injury. • Sevoflurane as opposed to propofol anesthesia preserved mitochondrial respiration. • Propofol anesthesia impeded mitochondrial function during myocardial ischemia. • A higher portion of complex I was in its deactive form during ischemia and sevoflurane anesthesia. Pharmacological interventions reducing myocardial ischemia and reperfusion (I/R) injury include the administration of anesthetics. Both sevoflurane as well as propofol have been shown to elicit cardiac protection via distinct molecular mechanisms. We investigated the hypothesis that sevoflurane in contrary to propofol anesthesia elicits cardiac protection against I/R-injury via mitochondrial mechanisms of disease. Male New Zealand white rabbits (n = 42) were subjected 30 min of coronary artery occlusion followed by 3 h of reperfusion. After induction with pentobarbital, the animals either received sevoflurane or propofol to maintain general anesthesia. Infarct size was determined gravimetrically after triphenyltetrazolium chlorid-staining. Cardiac mitochondria were isolated and mitochondrial oxygen consumption was measured using a Clark electrode. Mitochondrial respiratory chain complex activities (I-IV) were analyzed utilizing specific assays. Data are mean ± SD. Sevoflurane anesthesia significantly decreased the resulting myocardial infarct size compared to propofol anesthesia (p = 0.0275 vs. propofol). Mitochondria from animals receiving propofol anesthesia showed a significantly reduced mitochondrial respiratory control ratio (p = 0.01909 vs. sham) and impaired activities of respiratory complex I (p = 0.0147 vs. sham; p < 0.01 vs. sevoflurane) as well as respiratory complex IV (p = 0.0181 vs. sham). Mitochondrial dysfunction was absent in sevoflurane anesthesized animals. Furthermore, a significantly higher portion of complex I was found to be in its deactive form during I/R-injury in animals receiving sevoflurane anesthesia (p = 0.0123 vs. propofol). Sevoflurane as opposed to propofol anesthesia preserved mitochondrial respiration and elicited cardiac protection against I/R-injury. [ABSTRACT FROM AUTHOR]

Ginsenoside Rb1 (GRb1) is known to play an effective protection on myocardial infarction, yet its therapeutic mechanism on myocardial ischemia/reperfusion (I/R) injury has remained obscure. Here we sought to investigate the protective mechanism of GRb1 preconditioning on myocardial I/R injury in rats. We report here that GRb1 preconditioning could improve myocardial I/R injury induced-cardiac functions including LVDP, -dp/dt min and + dp/dt max; however, the heart rate (HR) was maintained at a level comparable to the I/R group. Additionally, in I/R injury group given GRb1 preconditioning, release of myocardial enzymes (CK-MB and Trop l) and CtsB was decreased. Moreover, GRb1 decreased the expression of apoptotic related proteins e.g. cleaved-caspase 3; however, the ratio of Bcl-2/Bax related to anti-apoptosis was decreased. The study was extended by injecting rapamycin intraperitoneally before GRb1 pretreatment. Thus, mTOR pathway was significantly upregulated after GRb1 pretreatment when compared with I/R. Remarkably, the anti-apoptosis protection of GRb1 pretreatment was attenuated by rapamycin. Furthermore, GRb1 effectively reduced the infarct size thus supporting its role in anti-myocardial I/R injury. It is concluded that GRb1 preconditioning can ameliorate myocardial I/R injury as manifested by the improvement of cardiac function indices; moreover, release of myocardial enzymes, namely, CK-MB, Trop l and CtsB was reduced. More importantly, we have shown that the protective effect of GRb1 against I/R injury induced cardiomyocyte apoptosis is associated with the activation of mTOR signal pathway as evident by the use of rapamycin. [ABSTRACT FROM AUTHOR]

Metoprolol (Met) is widely applied in the treatment of myocardial infarction and coronary heart disease in clinic. However, the metabolic network in vivo affected by Met manipulation is still unclear and it's therapeutic molecular mechanisms were remained to be furthered elucidated except β1 adrenergic receptor. Myocardial infarction (MI) was induced by permanent CAL for 24 h in ICR mice. Myocardial infarct size, biochemical indicators such as creatine kinase (CK), lactate dehydrogenase (LDH), C-reactive Protein (CRP), tumor necrosis factor-α (TNF-α) and cardiac troponin I(cTn-I), cardiac function and myocardial pathological changes were detected to ensure the improvement of Met on MI. Subsequently, the significantly changed endogenous metabolites and the network in both serum and urine were screened and constructed through metabolomics by using HPLC-Q-TOF/MS. Finally, the potential regulatory enzymes that could be the possible new therapeutic targets of Met were selected and validated by western blotting and immunohistochemistry based on the screened differential metabolites and the enrichment analysis. Met effectively reduced the infarct size of myocardial infarction mice, improved the biochemical indicators, and ameliorated the cardiac function and pathological conditions. Our study further found that Met could regulate the pathways of glycine, serine and threonine metabolism, cysteine and methionine metabolism, purine and pyrimidine metabolism under the pathological conditions of MI. Moreover, several regulatory enzymes involved GATM, CSE and NT5E were demonstrated to be regulated by Met. This study constructed the regulatory metabolic network map of Met, elucidated the endogenous metabolic pathway regulated by Met, and validated the new potential therapeutic targets of Met in MI, which might provide a further reference for the clinical application of Met. [ABSTRACT FROM AUTHOR]

• MiR-200a is upregulated and responsible for the apoptosis in AMI models. • The inhibition of miR-200a protects cardiomyocytes against apoptosis. • MiR-200a derived signaling pathway is potential therapeutic target for AMI. Acute myocardial infarction (AMI) is a major clinical manifestation of ischemic heart disease and represents a significant cause of morbidity and mortality. However, key regulators in the pathogenesis of ischemic heart disease remain controversial. The present study was designed to investigate the involvement of miR-200a and its related mechanism in AMI. Left coronary artery (LCA) ligation was conducted to induce an AMI mouse model. The infarct size was measured by TTC staining. H 2 O 2 was used to induce an AMI model in vitro. miR-200a mimics, anti-miR-200a antisense oligodeoxyribonucleotides (AMO-200a), as well as corresponding negative controls were transfected into cardiomyocytes to observe the effect of miR-200a. Flow cytometry was used to detect cell apoptosis. Real-time PCR, immunofluorescence and western blot assays were used to evaluate gene expression at RNA or protein levels, respectively. Apoptosis was activated in AMI models. The expression of miR-200a was upregulated both in the peri-infarcted region of mice myocardium and H 2 O 2 -treated cardiomyocytes. The co-administration of AMO-200a decreased the number of apoptosis cells and altered the expression of apoptosis related proteins. Interestingly, bioinformatics analysis results revealed that miR-200a could bind to the 3′-untranslated regions (3'-UTR) of Fus mRNA. In addition, the expression of Fus was downregulated in the AMI mouse models and in H 2 O 2 -treated cardiomyocytes. The alteration of miR-200a negatively regulated Fus expression in cardiomyocytes. Also, the protective effect of AMO-200a was observed through its regulation of Fus. MiR-200a-dependent apoptosis signaling pathway plays an important role in the pathogenesis of AMI injury and could be an exciting potential therapeutic target. [ABSTRACT FROM AUTHOR]

Tongguan Capsule, a traditional Chinese medicine, is safe to use and is efficient in treating ischemic heart diseases. The present study aimed to investigate whether Tongguan capsule derived-herb (TGD) can mitigate left ventricular remodeling and dysfunction in post myocardial infarction (MI) rats as well as reduce arrhythmias. MI was induced by a ligation of the left anterior descending coronary artery. TGD was administered to the post-MI rats over a period of 4 weeks. TGD treatment significantly attenuated tachyarrhythmia inducibility and cardiac dysfunction in post-MI heart. Echocardiogram showed that TGD significantly reduced the development of ventricular remodeling. Histological study revealed that TGD significantly reduced myocardial interstitial collagen deposition, myocyte area and α-smooth muscle actin (α-SMA) expression, and increased connexin 43 expression in the infarcted border zone (IBZ). Western blotting results revealed that TGD treatment significantly down-regulated the protein expression levels of type I and III collagen, α-SMA, and up-regulated connexin 43. RT-qPCR results showed that TGD decreased the levels of ANP and BNP. These findings provided strong evidences that TGD intervention ameliorated interstitial fibrosis, myocyte hypertrophy and gap junction expression in the IBZ, attenuated left ventricular remodeling and dysfunction, and reduced vulnerability to tachyarrhythmia. TGD inhibited IBZ remodeling by its inhibition effect on myofibroblasts differentiation. [ABSTRACT FROM AUTHOR]

• Anesthetic propofol interfere with the cardioprotective effects induced by remote preconditioning of trauma (RPCT). • Cardiac TRPV1 activation may be involved in RPCT induced cardioprotective effects. • Propofol should be carefully used as an anesthetic choice while conducting RPCT induced cardioprotection. Remote preconditioning of trauma (RPCT) by surgical incision is an effective cardioprotective strategy via the transient receptor potential vanilloid 1 (TRPV1) channel as a form of remote ischemic preconditioning (RIPC). However, cardioprotection by RIPC has been shown to be completely blocked by propofol. We thus hypothesized that propofol may interfere with RPCT induced cardioprotection, and that RPCT induces cardioprotection via the cardiac TRPV1 channel. Male Sprague-Dawley rats were subjected to 30 min of myocardial ischemia followed by 2 h of reperfusion. RPCT was achieved by a transverse abdominal incision. Additionally, propofol or the TRPV1 receptor inhibitor capsazepine (CPZ) was given before RPCT. Infarct size was assessed by triphenyltetrazolium staining. Heart TRPV1 expression was detected by Western blot and immunofluorescence. RPCT significantly reduced infarct size compared to control treatment (45.6 ± 4% versus 65.4 ± 2%, P < 0.01). This protective effect of RPCT was completely abolished by propofol and CPZ. TRPV1 channels are present in the heart. Therefore, cardioprotection by RPCT is also abolished by propofol, and cardiac TRPV1 mediates this cardioprotection. [ABSTRACT FROM AUTHOR]

Abstract Myocardial ischemia/reperfusion injury (IRI) has long been identified to be a contributor to adverse cardiovascular outcomes following myocardial ischemia, cardiac surgery or circulatory arrest. This study aims to investigate the effects of microRNA (miR-370) targeting perilipin-5 (PLIN5) in mice following sevoflurane anesthetic preconditioning (SAP). A mouse model of left ventricular myocardial IRI was established, followed by the evaluation of myocardial infarction size and cardiac function to determine the effects of SAP. The underlying regulatory mechanisms of miR-370 were analyzed in concert with the treatment of miR-370 mimic, miR-370 inhibitor, or siRNA against PLIN5 in cardiomyocytes isolated from mice with IRI. Also, cardiomyocyte proliferation, cell cycle distribution and apoptosis were evaluated following treatment. Lastly, SAP-treated I/R mice were injected with miR-370 inhibitor to verify the mechanism of SAP. The use of SAP conferred cardioprotective effects on myocardial IRI. MiR-370 was downregulated in mice that exhibited IRI, but SAP elevated the miR-370 expression. Functionally, miR-370 negatively targeted PLIN5 and activated the peroxisome proliferator activated-receptor (PPAR) signaling pathway, leading to decreased PPARγ expression but increased PPARα expression. The results also showed that elevation of miR-370 or the silencing of PLIN5 promoted cardiomyocyte proliferation. miR-370 also inhibited cardiomyocyte apoptosis as reflected by decreased caspase-3 expression and increased Bcl-2 expression. Additionally, SAP also alleviated I/R injury by inhibiting PPARγ. This study demonstrates that SAP induces miR-370 and exerts cardioprotective effects on myocardial IRI, where upregulation of miR-370 alleviates myocardial IRI via inhibiting the PLIN5-dependent PPAR signaling pathway. [ABSTRACT FROM AUTHOR]