NAD+-A Hub of Energy Metabolism in Heart Failure.

Heart failure is a condition where reduced levels of adenosine triphosphate (ATP) affect energy supply in myocardial cells. Nicotinamide adenine dinucleotide (NAD+) plays a crucial role as a coenzyme for electron transfer in energy metabolism. Decreased NAD+ levels in myocardial cells lead to inadequate ATP production and increased susceptibility to heart failure. Researchers are exploring ways to increase NAD+ levels to alleviate heart failure. Targets such as sirtuin2 (sirt2), sirtuin3 (sirt3), Poly (ADP-ribose) polymerase (PARP), and diastolic regulatory proteins are being investigated. NAD+ supplementation has shown promise, even in heart failure with preserved ejection fraction (HFpEF). By focusing on NAD+ as a central component of energy metabolism, it is possible to improve myocardial activity, heart function, and address energy deficiency in heart failure.

Mechanism of CD38 via NAD+ in the Development of Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, and it can proceed to cirrhosis and hepatocellular carcinoma, as well as cardiovascular disease, chronic renal disease, and other complications, resulting in a massive economic burden. At the moment, nicotinamide adenine dinucleotide (NAD+) is thought to be a possible treatment target for NAFLD, besides Cluster of differentiation 38(CD38) is the primary NAD+ degrading enzyme in mammals and may play a role in the pathophysiology of NAFLD. For example, CD38 regulates Sirtuin 1 activity and hence affects inflammatory responses. CD38 inhibitors enhance glucose intolerance and insulin resistance in mice and lipid accumulation in the liver is greatly decreased in CD38-deficient mice. This review describes the role of CD38 in the development of NAFLD in terms of Macrophage-1, insulin resistance, and abnormal lipid accumulation in order to offer recommendations for future NAFLD pharmacological trials.

Joint efficacy of the three biomarkers SNCA, GYPB and HBG1 for atrial fibrillation and stroke: Analysis via the support vector machine neural network.

Atrial fibrillation (AF) is the most common type of persistent arrhythmia. Although its incidence has been increasing, the pathogenesis of AF in stroke remains unclear. In this study, a total of 30 participants were recruited, including 10 controls, 10 patients with AF and 10 patients with AF and stroke (AF + STROKE). Differentially expressed genes (DEGs) were identified, and functional annotation of DEGs, comparative toxicogenomic database analysis associated with cardiovascular diseases, and predictions of miRNAs of hub genes were performed. Using RT-qPCR, biological process and support vector machine neural networks, numerous DEGs were found to be related to AF. HBG1, SNCA and GYPB were found to be upregulated in the AF group. Higher expression of hub genes in AF and AF + STROKE groups was detected via RT-PCR. Upon training the biological process neural network of SNCA and GYPB for HBG1, only small differences were detected. Based on the support vector machine, the predicted value of SNCA and GYPB for HBG1 was 0.9893. Expression of the hub genes of HBG1, SNCA and GYPB might therefore be significantly correlated to AF. These genes are involved in the incidence of AF complicated by stroke, and may serve as targets for early diagnosis and treatment.

Manifestation of cardiac injury in hospitalised patients with COVID-19.

BACKGROUND: COVID-19 has been sweeping the world since it emerged in late December 2019. However, little is known about cardiac injury in hospitalised COVID-19 patients. This study is to investigate the incidence and characteristics of myocardial injury in COVID-19 patients admitted in hospital. METHODS: Fifty-four COVID-19 patients were enrolled in one ward in Tongji Hospital, Wuhan, China, and 5 were excluded caused by missing cardiac troponin I levels. Forty-nine participants were included in the final analysis. The clinical manifestations of hospitalised patients were analysed. Patients were divided into two groups, cardiac injury group and non-cardiac injury group, based on whether cardiac troponin I was elevated. Epidemic characteristics and laboratory test results were analysed in these two group. RESULTS: The average age of patients in the cardiac injury group was older (68.0 years old) than that in the non-cardiac injury group (61.5 years old). The percentages of patients with diabetes and critically severe pneumonia in the cardiac injury group were 38.5% and 38.5% respectively. Lymphocytes were decreased in 53.1% of all enrolled patients, but this decrease was more prominent (76.9%) in the cardiac injury group than the non-cardiac injury group (44.4%). Patients in the cardiac injury group also had lower platelet counts. CONCLUSIONS: COVID-19 can cause cardiac injury in many patients. It is more common in older patients and patients with diabetes and is associated with a significant decrease in lymphocytes.

Thymoquinone reduces cardiac damage caused by hypercholesterolemia in apolipoprotein E-deficient mice.

BACKGROUND: Hypercholesterolemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that thymoquinone protected rats from doxorubicin-induced cardiotoxicity and cardiac damage. The aim of this study was to investigate the possible protective effects of thymoquinone against cardiac damage in apolipoprotein E knockout (ApoE-/-) mice. METHODS: Eight-week-old male ApoE-/- mice were randomly divided into three groups: control group fed a normal diet (ND group), a high cholesterol diet (HD group) or HD mixed with thymoquinone (HD + TQ group). All groups were fed the different diets for 8 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at - 80 °C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis. RESULTS: The metabolic characteristics of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-sensitivity C-reactive protein (hs-CRP) were lower in ApoE-/-HD + TQ mice than in ApoE-/- HD mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) gene and protein expression was lower in the heart tissue of ApoE-/-HD + TQ mice than in those of ApoE-/-HD mice. Furthermore, the levels of macrophages and pro-inflammatory cytokines were lower in the cardiac tissues of ApoE-/-HD + TQ mice than in those of ApoE-/-HD mice. CONCLUSIONS: These results indicate that thymoquinone may provide a potential therapeutic target for cardiac damage caused by hypercholesterolemia.

Coenzyme Q10 protects against hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient mice.

BACKGROUND: Hyperlipidemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that Coenzyme Q10(CoQ10) protects against cardiac damage in vivo. The aim of this study was to investigate the possible protective effects of CoQ10 against cardiac damage in apolipoprotein E-deficient (ApoE-/-) mice. METHODS: Eight-week-old male C57BL/6 and ApoE-/- mice were randomly divided into four groups: C57BL/6 mice fed a normal diet (C57BL/6 group); C57BL/6 mice fed a normal diet + CoQ10 (C57BL/6 + CoQ10 group); ApoE-/- mice fed a high-fat diet (ApoE-/- HD group), and ApoE-/- mice fed a high-fat diet + CoQ10 (ApoE-/- HD + CoQ10 group). All groups were fed the different diets for 16 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at - 80 °C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis. RESULTS: The metabolic parameters such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and triglycerides (TG) levels were lower in ApoE-/-HD + CoQ10 mice than in ApoE-/- HD mice. There were significant pathophysiological changes (H&E, PAS, Masson and CD68 staining) in ApoE-/- mice in the HD group compared with those in the HD + CoQ10 group. CoQ10 reduced HD-induced cardiac tissue damage via autophagy (p62 and LC3), as evidenced by immunoblotting, immunohistochemistry, and RT-qPCR. CoQ10 also inhibited inflammation (IL-6 and TNF-α) gene expression in ApoE-/- mice. CONCLUSIONS: These results indicate that CoQ10 is a potential therapeutic target for cardiac damage caused by hyperlipidemia.

Interleukin-18 deficiency protects against renal interstitial fibrosis in aldosterone/salt-treated mice.

Interleukin (IL)-18 is a member of the IL-1 family of cytokines and was described originally as an interferon γ-inducing factor. Aldosterone plays a central role in the regulation of sodium and potassium homoeostasis by binding to the mineralocorticoid receptor and contributes to kidney and cardiovascular damage. Aldosterone has been reported to induce IL-18, resulting in cardiac fibrosis with induced IL-18-mediated osteopontin (OPN). We therefore hypothesized that aldosterone-induced renal fibrosis via OPN may be mediated by IL-18. To verify this hypothesis, we compared mice deficient in IL-18 and wild-type (WT) mice in a model of aldosterone/salt-induced hypertension. IL-18(-/-) and C57BL/6 WT mice were used for the uninephrectomized aldosterone/salt hypertensive model, whereas NRK-52E cells (rat kidney epithelial cells) were used in an in vitro model. In the present in vivo study, IL-18 protein expression was localized in medullary tubules in the WT mice, whereas in aldosterone-infused WT mice this expression was up-regulated markedly in the proximal tubules, especially in injured and dilated tubules. This renal damage caused by aldosterone was attenuated significantly by IL-18 knockout with down-regulation of OPN expression. In the present in vitro study, aldosterone directly induced IL-18 gene expression in renal tubular epithelial cells in a concentration- and time-dependent manner. These effects were inhibited completely by spironolactone. IL-18 may be a key mediator of aldosterone-induced renal fibrosis by inducing OPN, thereby exacerbating renal interstitial fibrosis. Inhibition of IL-18 may therefore provide a potential target for therapeutic intervention aimed at preventing the progression of renal injury.

Improvement of the Immunity System Through Sports: Novel Regulatory Mechanisms for Hypertension.

Hypertension and its resulting target organ damage is a complex process associated with a range of physiological and molecular factors, including immune regulation. The profound effects of exercise on normal immune system function and the development and progression of hypertension are well known. This review aims to create new avenues for preventing and treating hypertension and its associated target organ damage. This narrative review emphasizes the role of exercise training in the prevention/treatment of hypertension development through immune response modulation and presents current perspectives on the available scientific evidence. Several studies have shown that exercise regulates hypertension by altering immune cells, which is partly attributable to the anti-inflammatory effects of exercise training. Regular exercise modifies immune modulation and could represent a new mechanism for regulating hypertension. Although the utilization of exercise training and the immune system in conjunction for treating and preventing hypertension is still in its early stages, current scientific literature indicates numerous potential physiological links between exercise training, the immune system, and hypertension.

Regulation of Sirtuins in Sepsis-Induced Myocardial Damage: The Underlying Mechanisms for Cardioprotection.

Sepsis is defined as "a life-threatening organ dysfunction caused by a dysregulated host response to infection". Although the treatment of sepsis has evolved rapidly in the last few years, the morbidity and mortality of sepsis in clinical treatment are still climbing. Sirtuins (SIRTs) are a highly conserved family of histone deacetylation involved in energy metabolism. There are many mechanisms of sepsis-induced myocardial damage, and more and more evidence show that SIRTs play a vital role in the occurrence and development of sepsis-induced myocardial damage, including the regulation of sepsis inflammation, oxidative stress and metabolic signals. This review describes our understanding of the molecular mechanisms and pathophysiology of sepsis-induced myocardial damage, with a focus on disrupted SIRTs regulation. In addition, this review also describes the research status of related therapeutic drugs, so as to provide reference for the treatment of sepsis.

Exercise training affects calcium ion transport by downregulating the CACNA2D1 protein to reduce hypertension-induced myocardial injury in mice.

Hypertension is a risk factor for cardiovascular disease, and exercise has cardioprotective effects on the heart. However, the mechanism by which exercise affects hypertension-induced myocardial injury remains unclear. Exercise response model of hypertension-induced myocardial injury in mice was analyzed using multiomics data to identify potential factors. The study found that serum Ca2+ and brain natriuretic peptide concentrations were significantly higher in the HTN (hypertension) group than in the control, HTN+MICT (moderate intensity continuous exercise), and HTN+HIIT (high intensity intermittent exercise) groups. Cardiac tissue damage and fibrosis increased in the HTN group, but exercise training reduced pathological changes, with more improvement in the HTN+HIIT group. Transcriptomic and proteomic studies showed significant differences in CACNA2D1 expression between the different treatment groups. HIIT ameliorated HTN-induced myocardial injury in mice by decreasing Ca2+ concentration and diastolizing vascular smooth muscle by downregulating CACNA2D1 via exercise.

NAD+ Protects against Hyperlipidemia-induced Kidney Injury in Apolipoprotein E-deficient Mice.

Background: Hyperlipidemia is an independent risk factor for kidney injury. Several studies have shown that nicotinamide adenine dinucleotide (NAD+) is an important coenzyme involved in normal body metabolism. Therefore, this study aimed to investigate the possible protective effects of NAD+ against hyperlipidemia-induced kidney injury in apolipoprotein Edeficient (ApoE-/-) mice.

Methods: Twenty-five eight-week-old male ApoE-/- mice were randomly assigned into four groups: normal diet (ND), ND supplemented with NAD+ (ND+NAD+), high-fat diet (HFD), and HFD supplemented with NAD+ (HFD+NAD+). The mice were subjected to their respective diets for a duration of 16 weeks. Blood samples were obtained from the inferior vena cava, collected in serum tubes, and stored at -80°C until use. Kidney tissues was fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the kidney tissues was snapfrozen in liquid nitrogen for Western blot analysis.

Results: Metabolic parameters (total cholesterol, triglycerides, low-density lipoprotein-cholesterol, creatinine, and blood urea nitrogen) were significantly higher in the HFD group compared to the other groups. Histological analysis revealed prominent pathological manifestations in the kidneys of the HFD group. The HFD+NAD+ group showed increased levels of oxidative stress markers (NRF2 and SOD2) and decreased levels of NOX4 compared to the HFD group. Furthermore, the HFD group exhibited higher levels of TGF-ß, Smad3, Collagen I, Collagen III, Bax, and Bak compared to the other groups. NAD+ supplementation in the HFD+NAD+ group significantly increased the levels of SIRT3, HO-1, Bcl-2, and Bcl-xL compared to the HFD group. Additionally, NF-κB protein expression was higher in the HFD group than in the HFD+NAD+ group.

Conclusion: These findings demonstrated that NAD+ may hold potential as a clinical treatment for kidney injury caused by hyperlipidemia.

Beat-by-Beat Estimation of Hemodynamic Parameters in Left Ventricle Based on Phonocardiogram and Photoplethysmography Signals Using a Deep Learning Model: Preliminary Study.

Beat-by-beat monitoring of hemodynamic parameters in the left ventricle contributes to the early diagnosis and treatment of heart failure, valvular heart disease, and other cardiovascular diseases. Current accurate measurement methods for ventricular hemodynamic parameters are inconvenient for monitoring hemodynamic indexes in daily life. The objective of this study is to propose a method for estimating intraventricular hemodynamic parameters in a beat-to-beat style based on non-invasive PCG (phonocardiogram) and PPG (photoplethysmography) signals. Three beagle dogs were used as subjects. PCG, PPG, electrocardiogram (ECG), and invasive blood pressure signals in the left ventricle were synchronously collected while epinephrine medicine was injected into the veins to produce hemodynamic variations. Various doses of epinephrine were used to produce hemodynamic variations. A total of 40 records (over 12,000 cardiac cycles) were obtained. A deep neural network was built to simultaneously estimate four hemodynamic parameters of one cardiac cycle by inputting the PCGs and PPGs of the cardiac cycle. The outputs of the network were four hemodynamic parameters: left ventricular systolic blood pressure (SBP), left ventricular diastolic blood pressure (DBP), maximum rate of left ventricular pressure rise (MRR), and maximum rate of left ventricular pressure decline (MRD). The model built in this study consisted of a residual convolutional module and a bidirectional recurrent neural network module which learnt the local features and context relations, respectively. The training mode of the network followed a regression model, and the loss function was set as mean square error. When the network was trained and tested on one subject using a five-fold validation scheme, the performances were very good. The average correlation coefficients (CCs) between the estimated values and measured values were generally greater than 0.90 for SBP, DBP, MRR, and MRD. However, when the network was trained with one subject's data and tested with another subject's data, the performance degraded somewhat. The average CCs reduced from over 0.9 to 0.7 for SBP, DBP, and MRD; however, MRR had higher consistency, with the average CC reducing from over 0.9 to about 0.85 only. The generalizability across subjects could be improved if individual differences were considered. The performance indicates the possibility that hemodynamic parameters could be estimated by PCG and PPG signals collected on the body surface. With the rapid development of wearable devices, it has up-and-coming applications for self-monitoring in home healthcare environments.

Effects of Nicotinamide Adenine Dinucleotide on Older Patients with Heart Failure.

Background: Heart failure (HF) is the main cause of death in middle-aged and older people and is characterized by high morbidity, high mortality, a high rehospitalization rate, and many high-risk groups. Nicotinamide adenine dinucleotide (NAD+) is widely present in the mitochondria of cardiomyocytes and maintains the redox balance in the body, which can effectively treat HF. We sought to evaluate whether NAD+ therapy has some clinical efficacy in patients with HF. Methods: Based on using conventional drugs to treat HF, patients (n = 60) were randomized 1:1 to saline and 50 mg NAD+ with 50 mL of normal saline for 7 days. The baseline characteristics of patients before and after treatment and cardiac function (N-terminal pro B-type natriuretic peptide (NT-proBNP) level and left ventricular ejection fraction (LVEF) value) were analyzed. Serological analysis (sirtuin-1 (SIRT1), sirtuin-3 (SIRT3), sirtuin-6 (SIRT6), reactive oxygen species (ROS), and endothelin) was also performed. Results: Among the 60 patients with HF who were treated with NAD+ for 7 days, the improvement rate in NT-proBNP levels and LVEF values was better than in the saline group, although not statistically significant. These patients were more likely to benefit from NAD+ because of higher levels of anti-oxidative stress (SIRT1, SIRT3, SIRT6, and ROS) and anti-endothelial injury (endothelin) than those in the saline control group. Conclusions: According to the results of this study, it is believed that 7 days of NAD+ injections has a positive effect on improving cardiac function, oxidative stress, and endothelial injury in patients with HF compared with the saline control. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/) ChiCTR2300074326; retrospectively registered on 3 August 2023.

The Role of NAD+ in Myocardial Ischemia-induced Heart Failure in Sprague-dawley Rats and Beagles.

INTRODUCTION: Nicotinamide adenine dinucleotide (NAD+) participates in various processes that are dysregulated in cardiovascular diseases. Supplementation with NAD+ may be cardioprotective. However, whether the protective effect exerted by NAD+ in heart failure (HF) is more effective before acute myocardial infarction (MI) or after remains unclear. The left anterior descending arteries of male Sprague Dawley rats and beagles that developed HF following MI were ligated for 1 week, following which the animals were treated for 4 weeks with low, medium, and high doses of NAD+ and LCZ696. METHODS: Cardiac function, hemodynamics, and biomarkers were evaluated during the treatment period. Heart weight, myocardial fibrosis, and MI rate were measured eventually. RESULTS: Compared with the HF groups, groups treated with LCZ696 and different doses of NAD+ showed increased ejection fractions, fractional shortening, cardiac output, and stroke volume and decreased end-systolic volume, end-systolic dimension, creatine kinase, and lactic dehydrogenase. LV blood pressure was lower in the HF group than in the control group, but this decrease was significantly greater in the medium and high NAD+ dose groups. CONCLUSION: The ratios of heart weight indexes, fibrotic areas, and MI rates in the CZ696 and medium and high NAD+ dose groups were lower than those in the HF group. Medium and highdose NAD+ showed superior positive effects on myocardial hypertrophy, cardiac function, and myocardial fibrosis and reduced the MI rate.

Corrigendum: Regional myocardial work measured by echocardiography for the detection of myocardial ischemic segments: a comparative study with invasive fractional flow reserve.

[This corrects the article DOI: 10.3389/fcvm.2022.813710.].

NAD+: A key metabolic regulator with great therapeutic potential for myocardial infarction via Sirtuins family.

Myocardial infarction (MI) is one of the complex phenotypes of coronary artery disease, which results from the interaction of multiple genetic and environmental factors. Nicotinamide Adenine Dinucleotide (NAD+) is an important cofactor regulating metabolic homeostasis and a rate-limiting substrate for sirtuin (SIRT) deacetylase. Numerous NAD+ studies have shown that it can be used as an anti-MI treatment. However, there have been few systematic reviews of the overall role of NAD+ in treating MI. MI, which has long been a global health problem, still lacks effective treatment till now, and the discovery of NAD+ provides a new perspective on its adjuvant treatment. This review summarizes the role of NAD+ signaling in SIRTs in alleviating MI.

Advances in Exercise Therapy in Hemodialysis: A Systematic Review.

BACKGROUND: The main and common treatment of renal replacement therapy (RRT) for chronic kidney disease (CKD), especially in end-stage kidney disease (ESKD) patients, is hemodialysis (HD). Many reports have shown that exercise therapy is good for HD patients. This review aims to describe recent advances in exercise therapy in HD patients. OBJECTIVE: Our key opinions have focused on varied types of exercise therapy and identified barriers to exercise therapy among HD patients. Exercise implementation includes aerobic exercise training, resistance exercise training, combined exercise training, and novel exercise interventions. Barriers include internal and external distress, such as HD patients' restrictions and environmental problems. METHODS: This review is based on the novel/ most findings in PubMed, Web of Science, Google Scholar, and MEDLINE from the inception of every database until August 2022. RESULTS: The systematic search strategy identified 6 articles that met the inclusion criteria. Four were specific to exercise therapy in HD, and three were to exercise barriers in HD. Massive evidence has demonstrated exercise therapy for HD has specific benefits and neglectful causes of exercise barriers. CONCLUSION: In this review, we aimed to summarize recent advances in individual exercise therapy recommendations (type, intensity, time, and frequency) and exercise barriers in HD patients. In conclusion, Low/moderate-intensity exercise trained for at least thirty minutes five times per week, including aerobic exercise (Walking, Jogging, Swimming, and Health Exercises), resistance training (Dumbbells, Band training, and Knee extension), and combination exercise (both) during the first 2 hours of dialysis treatment or non-dialysis days is advisable treatment recommendation.

Different exercise training intensities prevent type 2 diabetes mellitus-induced myocardial injury in male mice.

Type 2 diabetes mellitus (T2DM) usually develop myocardial injury and that exercise may have a positive effect on cardiac function. However, the effect of exercise intensity on cardiac function has not yet been fully examined. This study aimed to explore different exercise intensities on T2DM-induced myocardial injury. 18-week-old male mice were randomly divided into four groups: a control group, the T2DM, T2DM + medium-intensity continuous training (T2DM + MICT), and T2DM + high-intensity interval training (T2DM + HIIT) groups. In the experimental group, mice were given high-fat foods and streptozotocin for six weeks and then divided into two exercise training groups, in which mice were subjected to exercise five days per week for 24 consecutive weeks. Finally, metabolic characteristics, cardiac function, myocardial remodeling, myocardial fibrosis, oxidative stress, and apoptosis were analyzed. HIIT treatment improved cardiac function and improved myocardial injury. In conclusion, HIIT may be an effective means to guard against T2DM-induced myocardial injury.

Luteolin reduces cardiac damage caused by hyperlipidemia in Sprague-Dawley rats.

Objective: Hyperlipidemia is a risk factor for cardiac damage that can lead to many cardiovascular diseases. A recent study reported the cardioprotective effects of luteolin in vitro and in vivo. In this study, we aimed to investigate the possible protective effects of luteolin against hyperlipidemia-induced cardiac damage in Sprague-Dawley (SD) rats. Methods: Six-week-old male SD rats were randomly divided into five groups: a normal diet (ND) group; a high-fat diet (HFD) group; and three high-fat diet mixed with luteolin (HFD + LUT) groups, where in a luteolin dosage 50, 100, or 200 mg/kg/day was administered. All groups were fed their respective diets for 12 weeks. Results: Left ventricular ejection fraction and fractional shortening (parameters of cardiac function) were lower in the HFD + LUT (100 mg/kg/day) group than in the HFD group. Metabolic parameters were lower in the HFD + LUT (100 mg/kg/day) group than in the HFD group. Collagen I, collagen III, and TGF-ß expression levels were lower in the cardiac tissues of the HFD + LUT (100 mg/kg/day) group, compared to those of the HFD group. Expression of the profibrotic genes MMP2 and MMP9 was suppressed in the cardiac tissues of the HFD + LUT (100 mg/kg/day) group, compared to those of the HFD group. Furthermore, CD36 and lectin-like oxidized low-density lipoprotein receptor-1 protein levels were lower in the cardiac tissues of the HFD + LUT (100 mg/kg/day) group, compared to those of the HFD group. Conclusion: These findings would provide new insights into the role of luteolin in hyperlipidemia-induced cardiac damage and contribute to the development of novel therapeutic interventions to treat cardiovascular disease progression.

Exercise reduces hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient mice via its effects against inflammation and oxidative stress.

Cardiovascular disease is a high incidence and mortality rate disease worldwide. Exercise training has become an established evidence-based treatment strategy that is beneficial for many cardiovascular diseases. This study aimed to investigate the effects of exercise on hyperlipidemia-induced cardiac damage in apolipoprotein E-deficient (ApoE-/-) mice. Male ApoE-/- mice were randomly divided into the following four groups: normal diet (ND), normal diet + exercise training (ND + E), high-fat diet (HFD), and high-fat diet + exercise training (HFD + E). Exercise training consisted of swimming for 40 min, 5 days/week for 12 weeks. After 12 weeks, histopathological alterations in cardiac tissue and the serum were measured. Furthermore, the NOX4, NRF2, SIRT1, TGF-ß, HO-1, collagen III, Smad3, Bax, Bak, Bcl-2, Bcl-xl, IL-1ß, IL-6, and IL-18 expression levels were evaluated using immunohistochemistry and western blotting; Results: the serum levels of SIRT1, GSH-Px, and SOD were lower in ApoE-/- HFD mice compared with those in ApoE-/- HFD + E mice. Significant pathological changes were observed in the ApoE-/- HFD + E group compared with those in the ApoE-/- HFD group. Increased levels of oxidative stress, fibrosis, and apoptosis, and decreased antioxidant expression in the ApoE-/- HFD group compared with those in ApoE-/- HFD + E mice. Exercise exerts protective effects against cardiac damage caused by hyperlipidemia.