Obesity is an independent risk factor of cardiovascular diseases. Epidemiological studies have shown that obesity induces the production of inflammatory factors and changes in cardiac hemodynamics, remodeling and function, leading to myocardial damage and heart diseases. The positive effect of exercise on the cardiovascular system has been widely confirmed, while the acute cardiovascular stress caused by exercise cannot be ignored. Compared with the general population, obese people were more prone to arrhythmia and have a higher risk of cardiovascular events during exercise, due to their abnormal cardiac function, myocardial pathological remodeling and low tolerance to corresponding stress. Studies have shown that the intervention of exercise preconditioning (EP) can effectively reduce such risks. EP increases myocardial oxygen consumption through short-term exercise, resulting in relative or absolute myocardial ischemia, inducing the intrinsic myocardial protective effect and reducing the continuous ischemia caused by subsequent long-term exercise. This article reviews the obesity-induced abnormal changes of cardiac function and structure, possible exercise- induced risks of cardiovascular events in obese people and the role of EP in reducing exercise-induced risks of cardiovascular events. We summarize the progress on EP models in obese people, EP prevention against adverse cardiovascular events in obese people, with the aim to provide a theoretical basis for the application of EP in obese people.
Humans ; Exercise ; Obesity ; Myocardium/pathology* ; Myocardial Ischemia ; Cardiovascular Diseases

This study established the EA.hy926 cell myocardial ischemia model to compare the effects of two Kaixin Powder prescriptions, Buxin Decoction(BXD) and Dingzhi Pills(DZP), at three dosages(500, 200, and 100 μg·mL~(-1)) on the cell viability. Further, the public databases(TCMSP, TCMID, SYMMAP, and STRING) and the network pharmacology methods such as KEGG pathway enrichment were employed to decipher the possible molecular mechanism of BXD in exerting the cardioprotective effect. The pharmacological effect of BXD was evaluated with the rat model of isoprenaline(ISO)-induced myocardial ischemia. The expression levels of proteins involved in the phosphatidylinositol-3-kinase/protein kinase B(PI3 K/AKT) signaling pathway were measured by Western blot. BXD significantly increased the viability of EA.hy926 cells, showing the performance superior to DZP. The network pharmacology analysis predicted that BXD might exert cardiac protection through the PI3 K/AKT signaling pathway. The in vivo experiment on rats showed that BXD treatment significantly increased the cardiac ejection fraction(EF), fractional shortening(FS), diastolic left ventricular anterior wall(LVAWd), systolic left ventricular anterior wall(LVAWs), and diastolic left ventricular posterior wall(LVPWd), significantly decreased the beat per minute(BPM) and diastolic left ventricular internal diameter(LVIDd), and significantly improved the ST segment in the electrocardiogram. The pathological results(Masson staining) showed that BXD restored the myocardial thickness, decreased the collagen fiber, increased the muscle fiber, and reduced the infarct area to alleviate myocardial ischemia. Furthermore, BXD lowered the serum levels of inflammatory cytokines [tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6)] and myocardial enzymes [creatine kinase(CK) and lactate dehydrogenase(LDH)], increased the p-AKT/AKT ratio, up-regulated the protein levels of PI3 K, NF-κB, IKK-α, and Bcl-xl, and down-regulated that of the apoptotic protein Bax. In conclusion, BXD may exert cardiac protection effect by regulating the PI3 K/AKT signaling pathway.
Rats ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Powders ; Network Pharmacology ; Signal Transduction ; Myocardial Ischemia ; Myocardium/pathology* ; Creatine Kinase ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Prescriptions

OBJECTIVE: To examine the effect of Shenmai Injection (SMJ) on ferroptosis during myocardial ischemia reperfusion (I/R) injury in rats and the underlying mechanism. METHODS: A total of 120 SPF-grade adult male SD rats, weighing 220-250 g were randomly divided into different groups according to a random number table. Myocardial I/R model was established by occluding the left anterior descending artery for 30 min followed by 120 min of reperfusion. SMJ was injected intraperitoneally at the onset of 120 min of reperfusion, and erastin (an agonist of ferroptosis), ferrostatin-1 (Fer-1, an inhibitor of ferroptosis) and ML385 (an inhibitor of nuclear factor erythroid-2 related factor 2 (Nrf2)) were administered intraperitoneally separately 30 min before myocardial ischemia as different pretreatments. Cardiac function before ischemia, after ischemia and after reperfusion was analysed. Pathological changes in the myocardium and the ultrastructure of cardiomyocytes were observed, and the myocardial infarction area was measured. Additionally, the concentration of Fe²⁺ in heart tissues and the levels of creatine kinase-MB (CK-MB), troponin I (cTnl), malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were measured using assay kits, and the expressions of Nrf2, glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were examined by Western blot. RESULTS: Compared with the sham group, I/R significantly injured heart tissues, as evidenced by the disordered, ruptured and oedematous myocardial fibres; the increases in infarct size, serum CK-MB, cTnI and MDA levels, and myocardial Fe²⁺ concentrations; and the decreases in SOD activity (P<0.05). These results were accompanied by ultrastructural alterations to the mitochondria, increased expression of ACSL4 and inhibited the activation of Nrf2/GPX4 signalling (P<0.05). Compared with I/R group, pretreatment with 9 mL/kg SMJ and 2 mg/kg Fer-1 significantly reduced myocardial I/R injury, Fe²⁺ concentrations and ACSL4 expression and attenuated mitochondrial impairment, while 14 mg/kg erastin exacerbated myocardial I/R injury (P<0.05). In addition, cardioprotection provided by 9 mL/kg SMJ was completely reversed by ML385, as evidenced by the increased myocardial infarct size, CK-MB, cTnI, MDA and Fe²⁺ concentrations, and the decreased SOD activity (P<0.05). CONCLUSIONS Ferroptosis is involved in myocardial I/R injury. Pretreatment with SMJ alleviated myocardial I/R injury by activating Nrf2/GPX4 signalling-mediated ferroptosis, thereby providing a strategy for the prevention and treatment of ischemic heart diseases.
Animals ; Male ; Rats ; Coenzyme A ; Creatine Kinase ; Ferroptosis ; Ligases ; Malondialdehyde ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy* ; Myocardial Reperfusion Injury/pathology* ; Myocytes, Cardiac/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Rats, Sprague-Dawley ; Superoxide Dismutase/metabolism* ; Troponin I

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.
Animals ; Apoptosis ; Fibrosis ; Heart Failure/drug therapy* ; Inflammation/drug therapy* ; Male ; Mice ; Mice, Inbred C57BL ; Myocardial Ischemia/pathology* ; Oleanolic Acid/pharmacology*

OBJECTIVETo observe the effects of electroacupuncture (EA) on inflammatory reaction of acute myocardial ischemia (MI) in mice, and to explore its action mechanism.

METHODSForty adult male C57BL/6 mice were randomly divided into a control group, a sham operation group, a model group and an EA group, 10 mice in each one. The model was established in the model group and EA group by ligating the left anterior descending branch of coronary artery. The mice in the EA group were treated with EA at "Neiguan" (PC 6) with 2 mA of intensity and 2 Hz /100 Hz of frequency; EA was given 30 min per treatment, once a day for totally 5 days. The mice in the control group and model group were treated with immobilization and no EA was given. The mice in the sham operation group were not treated with ligating at the left anterior descending branch of coronary artery, but the remaining procedure was identical to the model group. The electrocardiogram was recorded and △ST was calculated to evaluate the model. TTC and HE staining methods were applied to evaluate the infarct size and pathologic change of myocardial tissue, respectively. Western blot method was applied to test the protein expression levels of tumor necrosis factor-α (TNF-α), nuclear factor-κB p65 (NF-κB p65), interleukin-1β (IL-1β) and interleukin-8 (IL-8).

RESULTSCompared with the sham operation group, the S-T segments in the model group and EA group were increased obviously after modeling (both <0.01), indicating the MI model was established successfully. The TTC and HE staining results indicated, compared with the sham operation group, the model group had larger infarction size (<0.01), more myocardial fibers injury and inflammatory infiltration; compared with the model group, the infarction size of the EA group was significantly reduced (<0.01), and the myocardial fibers injury and inflammatory infiltration were improved. Compared with the control group, the protein expression levels in the sham operation group were similar (all >0.05); compared with the sham operation group, the expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 were significantly increased in the model group (<0.01, <0.05); compared with the model group, the expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 were significantly reduced in the EA group (all <0.05).

CONCLUSIONEA might reduce the protein expression levels of TNF-α, NF-κB p65, IL-1β and IL-8 in cardiac muscle tissue to inhibit inflammatory reaction and achieve myocardial protective effect in mice with acute myocardial ischemia.

Animals ; Electroacupuncture ; Inflammation ; therapy ; Interleukin-1beta ; metabolism ; Interleukin-8 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Myocardial Ischemia ; therapy ; Myocardium ; pathology ; Random Allocation ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Previous studies have indicated that the Ilex genus exhibits antioxidant, neuroprotective, hepatoprotective, and anti-inflammatory activities. However, the pharmacologic action and mechanisms of Ilex cornuta against cardiac diseases have not yet been explored. The present study was designed to investigate the antioxidant and cardioprotective effects of Ilex cornuta root with in vitro and in vivo models. The anti-oxidative effects of the extract of Ilex cornuta root (ICR) were measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging and MTT assays as well as immunoassay. Furthermore, a rat model of myocardial ischemia was established to investigate the cardioprotective effect of ICR in vivo. Eight compounds were isolated and identified from ICR and exhibited DPPH free-radical scavenging activities. They also could increase cell viability and inhibit morphological changes induced by HO or NaSO in H9c2 cardiomyocytes, followed by increasing the SOD activities and decreasing the MDA and ROS levels. In addition, it could suppress the apoptosis of cardiomyocytes. In the rat model of myocardial ischemia, ICR decreased myocardial infarct size and suppressed the activities of LDH and CK. Furthermore, ICR attenuated histopathological alterations of heart tissues and the MDA levels, while increasing SOD activities in serum. In conclusion, these results suggest that ICR has cardioprotective activity and could be developed as a new food supplement for the prevention of ischemic heart disease.
Animals ; Antioxidants ; metabolism ; pharmacology ; therapeutic use ; Apoptosis ; Cardiovascular Agents ; pharmacology ; therapeutic use ; Cell Survival ; drug effects ; Hydrogen Peroxide ; metabolism ; Ilex ; Malondialdehyde ; metabolism ; Myocardial Infarction ; Myocardial Ischemia ; drug therapy ; metabolism ; pathology ; Myocardium ; cytology ; pathology ; Myocytes, Cardiac ; drug effects ; Oxidative Stress ; drug effects ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Roots ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism

BACKGROUND: Epidemiological studies show that immunoglobulin E (IgE) levels were higher in subjects with acute coronary events. However, it is unknown if the increased IgE level is a marker of future coronary incidents and whether it may be regarded as a risk factor of an ischemic heart disease. OBJECTIVE: Our aim was to investigate the relationship between IgE levels and some atherosclerotic markers in patients without known atherosclerotic disease. METHODS: Fifty patients (mean age, 40.96 ± 10.8 years) with high serum IgE levels due to various conditions who did not display evidence of an atherosclerotic disease and 30 healthy control subjects (mean age, 47 ± 8.27 years) were included in the study. Atherosclerotic disease markers including adhesion molecules like vascular cell adhesion molecule-1, intercellular adhesion molecule-1, proinflammatory cytokines such as interleukin-6, endothelin-1, and systemic inflammatory markers such as high sensitivity C-reactive protein were determined by enzyme-linked immunosorbent assay (ELISA). Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurements and carotid intima media thickness using transthoracic Doppler echocardiography.
Atherosclerosis ; C-Reactive Protein ; Carotid Intima-Media Thickness ; Coronary Vessels ; Cytokines ; Echocardiography, Doppler ; Endothelin-1 ; Enzyme-Linked Immunosorbent Assay ; Epidemiologic Studies ; Humans ; Immunoglobulin E ; Immunoglobulins ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; Myocardial Ischemia ; Pathology ; Risk Factors ; Vascular Cell Adhesion Molecule-1

OBJECTIVES: To explore the metabolic characteristics of lethal bradycardia induced by myocardial ischemia in rat's serum. METHODS: A rat myocardial ischemia-bradycardia-sudden cardiac death （MI-B-SCD） model was established, which was compared with the sham-operation group. The metabolic profile of postmortem serum was analyzed by gas chromatography-mass spectrometry （GC-MS）, coupled with the analysis of serum metabolic characteristics using metabolomics strategies. RESULTS: The serum metabolic profiles were significantly different between the MI-B-SCD rats and the control rats. Compared to the control rats, the MI-B-SCD rats had significantly higher levels of lysine, ornithine, purine, serine, alanine, urea and lactic acid; and significantly lower levels of succinate, hexadecanoic acid, 2-ketoadipic acid, glyceraldehyde, hexendioic acid and octanedioic acid in the serum. There were some correlations among different metabolites. CONCLUSIONS There is obvious metabolic alterations in the serum of MI-B-SCD rat. Both lysine and purine have a high value in diagnosing MI-B-SCD. The results are expected to provide references for forensic and clinical applications of prevention and control of sudden cardiac death.
Animals ; Bradycardia/pathology* ; Coronary Artery Disease ; Death, Sudden, Cardiac ; Disease Models, Animal ; Gas Chromatography-Mass Spectrometry/methods* ; Lysine/metabolism* ; Metabolomics/methods* ; Myocardial Ischemia/metabolism* ; Purines/metabolism* ; Rats

OBJECTIVETo explore the effects of principal-subordinate acupoints combination on improving myocardial ischemia, and the gene regulatory pathways for the protection of myocardial ischemia.

METHODSAccording to the random number table method, 70 SPF Wistar male rats were divided into a normal group, a model group, a LY294002 group, an insulin-like growth factors-1(IGF-1) group, a Neiguan group, an acupoint combination group and an acupoint combination + LY294002 group, 10 rats in each one. Rats in the normal group were injected with 0.9% NaCl solution, while rats in the remaining groups were treated with abdominal subcutaneous injection of isoroterenol hydrochloride to establish the rat model of myocardial ischemia. Rats in the LY294002 group and IGF-1 group were treated with injection of LY294002 solution and IGF-1 solution for 14 days. Rats in the Neiguan group were treated with electroacupuncture (EA) at "Neiguan" (PC 6) by using Han-200 EA apparatus for 10 min per treatment. Rats in the acupoint combination group were treated with EA at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) by using Han-200 EA apparatus for 10 min per treatment. Rats in the acupoint combination + LY294002 group were treated with LY294002 solution for 14 days, and EA at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) was given before model establishment, once a day for 21 days. EA pretreatment was given before model establishment in all acupuncture groups. The heart rate (HR) and ST segment voltage were detected before and after treatment; the myocardial pathological morphology was observed by HE staining; the expressions of P13K mRNA and Akt mRNA were tested.

RESULTSAfter modeling, HR and ST segment voltage in all intervention groups were higher than those in the normal group (all P < 0.01); after the intervention, the HR and the ST segment voltage in the acupoint combination group, IGF-1 group and IGF-1 group were improved (P < 0.01, P < 0.05), which was more significant in the acupoint combination group and Neiguan group (all P < 0.01). As for the myocardial pathological morphology, obvious myocardial ischemia was observed in the model group, and that in the LY294002 group was the most serious, and that in the acupoint combination+ LY294002 group was moderate. After intervention, the myocardial pathological damage in the IGF-1 group, Neiguan group and acupoint combination group was significant improved, which was more significant in the IGF-1 group and acupoint combination group. As for the expression of PI3K mRNA and Akt mRNA, compared with normal group, the expression of PI3K mRNA was increased in the remaining groups after modeling (P < 0.01, P < 0.05), which was more significant in the IGF-1 group and acupoint combination group (all P < 0. 01). The expression of Akt mRNA in the LY294002 group and acupoint combination + LY294002 group was reduced (P < 0. 01, P < 0.05), while that in the remaining groups was increased (P < 0.01, P < 0.05), which was more significant in the IGF-1 group and acupoint combination group (all P < 0.01).

CONCLUSIONThe principal-subordinate acupoints combination could improve heart rate and ST segment voltage in rats with chronic myocardial ischemia, reduce myocardial pathological damage, which is superior to single selection of "Neiguan" (PC 6). The PI3K/Akt signaling pathway may be involved in the regulation mechanism of principal-subordinate acupoints combination for the protection of chronic myocardial ischemia.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Chronic Disease ; therapy ; Electroacupuncture ; Electrocardiography ; Heart Rate ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Male ; Myocardial Ischemia ; enzymology ; pathology ; physiopathology ; therapy ; Myocardium ; pathology ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Rats ; Rats, Wistar

Coronary heart disease is a kind of heart disease that is caused by atherosclerosis. The lipid deposition in the vessel wall results in occlusion of coronary artery and stenosis, which could induce myocardial ischemia and oxygen deficiency. Intervention therapies like percutaneous coronary intervention (PCI) and coronary stent improve myocardial perfusion using catheter angioplasty to reduce stenosis and occlusion of coronary artery lumen. Accordingly, intervention therapies are widely applied in clinic to treat ischemic cardiovascular disease, arterial intima hyperplasia and other heart diseases, which could save the patients' life rapidly and effectively. However, these interventions also damage the original endothelium, promote acute and subacute thrombosis and intimal hyperplasia, and thus induce in-stent restenosis (ISR) eventually. Studies indicated that the rapid reendothelialization of damaged section determined postoperative effects. In this review, reendothelialization of implants after intervention therapy is discussed, including the resource of cells contributed on injured artery, the influences of implanted stents on hemodynamic, and the effects of damaged degree on reendothelialization.
Angioplasty, Balloon, Coronary ; Cardiac Catheterization ; Coronary Artery Disease ; therapy ; Coronary Restenosis ; prevention & control ; Endothelium, Vascular ; pathology ; Humans ; Myocardial Ischemia ; prevention & control ; Stents ; Thrombosis ; prevention & control