Cardiac Protective Effects Research Articles

Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling

Cancer immunotherapy has become a well-established treatment option for some cancers; however, its use is hampered by its cardiovascular adverse effects. Immune checkpoint inhibitors (ICIs)-related cardiac toxicity took place in kinds of different forms, such as myocarditis, acute coronary syndrome, and pericardial disease, with high mortality rates. This study aimed to investigate the roles of programmed death-1 (PD-1) inhibitor, one of widespread used ICIs, in the development of murine cardiac injury. PD-1 inhibitor is known to transduce immunoregulatory signals that modulate macrophages polarization to attack tumor cells. Hence, this study explored whether the cardiovascular adverse effects of PD-1 inhibitor were related to macrophage polarization. MicroRNA-34a (miR-34a), which appears to regulate the polarization of cultured macrophages to induce inflammation, is examined in cardiac injury and macrophage polarization induced by the PD-1 inhibitor. As a target of miR-34a, Krüppel-like factor 4 (KLF4) acted as an anti-inflammation effector to take cardiac protective effect. Further, it investigated whether modulating the miR-34a/KLF4-signaling pathway could influence macrophage polarization. The PD-1 inhibitor markedly induced M1 phenotype macrophage polarization with impaired cardiac function, whereas miR-34a inhibitor transfection treatment reversed M1 polarization and cardiac injury in vivo. In vitro, PD-1 inhibitor-induced M1 polarization was accompanied by an increase in the expression of miR-34a but a decrease in the expression of KLF4. TargetScan and luciferase assay showed that miR-34a targeted the KLF4 3′-untranslated region. Either miR-34a inhibition or KLF4 overexpression could abolish M1 polarization induced by the PD-1 inhibitor. The findings strongly suggested that the PD-1 inhibitor exerted its effect in promoting M1 polarization and cardiac injury by modulating the miR-34a/KLF4-signaling pathway and inducing myocardial inflammation. These findings might help us to understand the pathogenesis of cardiac injury during immunotherapy, and provide new targets in ameliorating cardiac injury in patients with cancer receiving PD-1 inhibitor treatment.

Identification of Hub Genes in Protective Effect of Astragaloside IV on Aconitine-Induced Cardiac Damage in Zebrafish Based on Bioinformatics Analysis.

Accumulating evidence suggests that Astragaloside IV (AS-IV) improves cardiac function and protects the cardiovascular system. However, the molecular targets involved remain ambiguous. In this work, we report research suggesting that AS-IV can antagonize arrhythmias and reduce the cardiac damage induced by aconitine in zebrafish. Zebrafish have certain benefits with respect to studying the effect of drugs on cardiovascular disease. The possible mechanisms involved are analyzed, and hub gene targets are predicted. First, a model of cardiac damage induced by aconitine was created, and then a safe drug concentration of AS-IV was screened, and the appropriate drug dose gradient was selected within a safe drug concentration range. Second, we confirmed the protective effect of AS-IV in the cardiovascular system by observing changes in zebrafish heart rates and the cardiac and vascular structure. Third, we aimed to demonstrate the antagonistic mechanism of AS-IV on heart rate and cardiac damage induced by aconitine in zebrafish, with differentially expressed genes (DEGs) detected by RNA sequencing. The DEGs were then further analyzed by bioinformatic techniques, such as function enrichment analysis, protein-protein interaction network, and DNA-microRNA networks, for example. Next, we predicted the hub genes of the cardiac protective effects of AS-IV. Finally, we validated these genes in different transcriptome sequence datasets of cardiac damage. Thus, we conclude that miR-26b-5p/ATF3/JUN are key targets of AS-IV and play an important role in maintaining cardiac homeostasis and regulating cardiac remodeling.

Why the Use of Angiotensin II May be a Fatal Mistake in COVID-19.

Why the Use of Angiotensin II May be a Fatal Mistake in COVID-19.

Exendin-4 protects the hearts of rats from ischaemia/reperfusion injury by boosting antioxidant levels and inhibition of JNK/p66 Shc/NADPH axis.

Exendin-4, a glucagon-like peptide-1 receptor agonist, was shown to protect against cardiac ischaemia/reperfusion (I/R) injury by suppressing oxidative stress. p66 Shc, a pro-oxidant and an apoptotic protein, is activated in the infarcted left ventricles (LVs) after induction of I/R. This study investigated if the cardiac protective effect of Exendin-4 against I/R injury in rats involves inhibition of p66 Shc and to determine the underlying mechanisms behind this. Adult male rats (n=12/group) were divided into four groups as a sham, a sham+Exendin-4, an I/R, and an I/R+Exendin-4. Exendin-4 was administered to rats 7days before the induction of I/R. Ischaemia was induced by ligating the left anterior descending (LAD) coronary artery for 40minutes followed by reperfusion for 10minutes. The infarct myocardium was used for further analysis. Exendin-4 significantly reduced infarct area (by 62%), preserved LV function and lowered serum levels of LDH and CK-MB in I/R-induced rats. Also, it significantly reduced LV levels of ROS and MDA and protein levels of cytochrome-c and cleaved caspase-3 but significantly increased levels of glutathione (GSH) and manganese superoxide dismutase (MnSOD) in LVs of I/R rats indicating antioxidant and anti-apoptotic effects. Furthermore, it inhibited JNK and p66 Shc activation and downregulated protein levels of p66 Shc and NADPH oxidase with no effect on protein levels/activity of p53 and PKCβII. Of note, Exendin-4 also increased GSH and MnSOD in LVs of control rats. In conclusion, Exendin-4 cardioprotective effect in I/R hearts is mediated mainly by antioxidant effect and inhibition of JNK/P66 Shc/NADPH oxidase.

Glypican‐1 Plays a Cardiac Protective Effect During Heart Failure Induced by Pressure Overload

About 1 in every 4 deaths is due to heart disease. Specifically, heart failure in its different forms impacts about 5.7 million people in the U.S. Hemodynamic pressure overload is a known cause for heart dysfunction and it may culminate in heart failure. Glypican‐1 (Gpc1) is a heparan sulfate proteoglycan that has mechanosensitive properties. Its role on heart function is not well understood but it may play a role on cardiac response to increased pressure. Herein we sought to investigate if deletion of Gpc1 contributes to cardiac dysfunction in a model of heart failure induced by pressure overload (Transverse Aortic Constriction, TAC). CD1 (wild type, WT) and Gpc1 knockout (Gpc1KO) mice were submitted to either a sham or TAC procedure. Heart function was assessed by echocardiography (ECHO) before (baseline), three and five weeks post‐surgery. The parameters analyzed by the ECHO were: stroke volume, cardiac output, left ventricle mass, left ventricle anterior wall during diastole (LVAWd), left ventricle posterior wall during diastole (LVPWd), left ventricle mean wall thickness (WTd), eccentricity, heart rate and ejection fraction. Baseline ejection fraction and heart rate was similar between WT and Gpc1KO. Baseline stroke volume, cardiac output and WTd were increased whereas eccentricity was decreased in Gpc1KO. Gpc1KO showed increased susceptibility to heart failure as evidenced by a faster and steep decrease in ejection fraction when compared to WT. In addition, Gpc1KO uniquely showed decreased stroke volume and cardiac output after 5 weeks of TAC. Left ventricle size was increased and eccentricity was decreased in the same time‐frame for both lines. Taken together, these results indicate that Gpc1 has a protective effect on cardiac function in a model of heart failure caused by pressure overload.Support or Funding InformationDepartment of Anesthesiology, College of Medicine, Tucson

Taurine protects against cardiac dysfunction induced by pressure overload through SIRT1–p53 activation

BackgroundHeart failure (HF) is an epidemic disease with increased incidence annually. It has been reported that taurine can improve cardiac function. This study investigated the cardioprotective effects of taurine in pressure-loaded HF mice and elucidated the possible mechanism. MethodsHF models were established by transverse aortic constriction (TAC). Animals were treated with either taurine for 9 weeks and/or the SIRT1 inhibitor EX527 (5 mg/kg/day, every 2days) after TAC operation. Cardiac function and geometry were revealed by echocardiography. Myocardial hypertrophy and fibrosis were assessed using Fluorescent wheat germ agglutinin (WGA) staining and Masson's trichrome staining. Western blot and RT-PCR were performed to elucidate the expression of target proteins and genes respectively. Apoptosis in cardiomyocytes was detected by TUNEL staining. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD) and malonyldialdehyde (MDA) and reactive oxygen species (ROS). Taurine concentrations and NAD+/NADH ratio were determined by taurine and NAD+/NADH assay kit. ResultsTaurine notably relieved cardiac dysfunction after TAC. The mechanisms were attributed to reduced myocyte hypertrophy and fibrosis, and alleviated apoptosis and oxidative stress. Meanwhile, taurine increased NAD+/NADH ratio，promoted the expression of SIRT1 and suppressed p53 acetylation. However, EX-527(inhibitor of SIRT1) decreased NAD+/NADH ratio and increased acetyl-p53 levels, and abolished the cardioprotective effects of taurine on mice subjected to TAC and increased apoptosis and oxidative stress. ConclusionThe mechanism responsible for cardiac-protective effects of taurine in HF induced by pressure overload is associated with the activation of the SIRT1–p53 pathway.

Evaluation of the Cardiac Protection Conferred by Proanthocyanidins in Grape Seeds against Development of Ehrlich Solid Tumors in Mice.

Examination of the antineoplastic effects of a range of chemical compounds is often undertaken via the transplantable tumor model of Ehrlich solid tumor (EST), which is a simulation of breast cancer. The purpose of this study was to explore how cardiac toxicity, damage, oxidative stress, and changes in the expressions of TNFα and apoptotic P53 triggered by EST could be countered with grape seed proanthocyanidins (GSPE). To that end, 50 female mice were used, with arbitrary and equal distribution into five groups, namely, the control group (G1), GSPE group (G2), EST group (G3), GSPE + EST (G4; cotreatment consisted of mice that received GSPE treatment at the beginning of EST induction over a period of 14 days), and EST + GSPE (G5; posttreatment consisted of mice with EST that received GSPE treatment for 14 days following the 14 days since the induction of EST). By comparison with the control group, the EST group had significantly higher levels of serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK), creatine kinase MB (CK-MB), myoglobin, cardiac TBARS, nitric oxide (NO), total thiol and hydrogen peroxide, cardiac damage, and expression of P53 and TNFα. On the other hand, the EST group had significantly lower levels of cardiac catalase and total antioxidant (TAC) than the control group. Furthermore, better improvement in cardiac toxicity, oxidative stress, damage, apoptosis, and TNFα expressions was displayed by the cotreated (GSPE + EST) group than by the posttreated (EST + GSPE) group. This led to the conclusion that GSPE conferred cardiac protective and antioxidant effects against EST. This finding calls for more investigation on the benefits of grape seeds as adjuvant agents to prevent and treat cardiac toxicity.

Effects of Eplerenone on Blood Pressure and Echocardiographic and Serum Biochemical Variables in Five Healthy Dogs: A Pilot Study.

Eplerenone (EP), an aldosterone antagonist, is reported to produce renal and cardiac protective effects in noncanine species. However, there are no detailed reports available on cardiovascular effects of EP in dogs. This study aimed to determine effect of EP on echocardiographic parameters, blood pressures, and biochemical variables in healthy dogs. Five healthy Beagle dogs were randomly divided and repeatedly used in each of 3 dose groups, receiving 2.5, 5, or 10 mg/kg BW EP orally q24 h for 4 wks. Serum biochemical test, blood pressure, and Doppler echocardiography measurements were performed before EP administration and at 1, 2, and 4 weeks after EP administration. Treatment with EP reduced mean blood pressure in a dose-dependent manner and significantly (but in a dose-independent manner) decreased left atrium/aorta ratio, early diastolic transmitral flow, early diastolic transmitral flow/late diastolic transmitral flow, peak velocity of early diastolic transmitral flow/peak velocity of early diastolic mitral annular motion, left ventricle and right ventricle Tei indices, stroke volume, cardiac output, and mid systole myocardial velocity gradient 1 to 4 weeks after administration. Deceleration time of early diastolic transmitral flow significantly increased after EP administration. No significant changes were observed in serum biochemical variables. The results indicated that EP might reduce preload, thereby decreasing left atrial size. In addition, reduction of left ventricular stiffness may have theoretically taken place but this could not be tested using the present study design. It is suggested that EP administration within the dose range used in this study is safe for administration to healthy dogs. Further studies are needed to explore both safety and efficacy, as well as to seek a recommended dose range of EP treatment in client-owned dogs with heart disease.

Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway

Context Baicalin is an active compound which demonstrates cardioprotection effects against myocardial ischaemia/reperfusion injury (MI/RI). Objective To investigate how baicalin protects against myocardial injury and to explore its potential mechanism. We hypothesized that baicalin-modulated macrophages change from M1 (pro-inflammatory subset) to M2 (anti-inflammatory subset) under I/R stress. Materials and methods We established an ischaemia/reperfusion (I/R) model using Sprague Dawley (SD) rat, then baicalin was intragastric administration (20, 60 or 120 mg/kg) for 24 h. The rats were randomly divided into five groups (n = 10): control, I/R, I/R + baicalin (20 mg/kg), I/R + baicalin (60 mg/kg) and I/R + baicalin (120 mg/kg). Cardiac function was detected by echocardiography, HE staining and ELISA, respectively. Macrophage phenotype was examined by flow cytometry. Furthermore, IHC, qRT-PCR and WB were employed to analyse the related mechanisms. Results The study showed that baicalin (20, 60 or 120 mg/kg) significantly improved cardiac function and impeded cardiac apoptosis in rats. In addition, the repair of myocardial morphology (reduced neutrophil infiltration) further confirmed its cardiacprotective effect. Moreover, baicalin effectively decreased iNOS, IL-1β and IL-6, and up-regulated Arg-1, IL-10 and TGF-β via changing the macrophage phenotype (from M1 towards M2). Notably, treatment with baicalin also inhibited the phosphorylation levels of JAK2 and STAT3. Discussion and conclusions: It was confirmed that baicalin alleviated post-I/R myocardial injury and reduced inflammation via JAK/STAT pathway, and baicalin treatment might be recommended as a new approach for myocardial ischaemic complications.

Thiopental sodium loaded solid lipid nano-particles attenuates obesity-induced cardiac dysfunction and cardiac hypertrophy via inactivation of inflammatory pathway

This work evaluates solid lipid nanoparticles of thiopental sodium against obesity-induced cardiac dysfunction and hypertrophy and explores the possible mechanism of action. TS loaded SLNs were formulated by hot-homogenization and solvent diffusion method. TS-SLNs were scrutinized for entrapment efficiency, drug loading capacity, gastric stability, particle size, in vitro drug release. Mice were feed with the normal chow or high-fat diet for 08 weeks to induce obesity and primary cardiomyocytes. The therapeutic effects of thiopental sodium in the high fat diet (HFD) induced cardiac hypertrophy. Systolic blood pressure (SBP) was estimated at a regular time interval. At the end of the experimental study, systolic pressure left ventricular, LV end-diastolic pressure and rate of increase of LV pressure and antioxidant, apoptosis, cytokines and inflammatory scrutinized. HFD induced group mice exhibited a reduction in the body weight and enhancement of cardiac hypertrophy marker and dose-dependent treatment of thiopental sodium up-regulation the body weight and down-regulated the cardiac hypertrophy. Thiopental sodium significantly (p < .001) dose-dependently altered the antioxidant, biochemical, cardiac parameters and remodeling. Thiopental sodium significantly (p < .001) dose-dependently reduced the SBP. Thiopental sodium altered the apoptosis marker, pro-inflammatory cytokines, inflammatory parameters along with reduced the p38-MAPK level. The cardiac protective effect of thiopental sodium shed light on future therapeutic interventions in obesity and related cardiovascular complications via inflammatory pathway.

The treatment effect of silymarin on heart damage in rats

Aim: In this article, we evaluated the possible cardiac protective effects of silymarin on valproic acid-induced heart injury by histological and biochemical parameters in rat heart.Material and Methods: The experiment was performed with 21 Sprague Dawley male rats. Rats were divided into three groups: group 1; control, group 2; valproic acid, group 3; valproic acid + silymarin. The groups received valproic acid 500 mg/kg/day per os (p.o.) and silymarin 100 mg/kg/day p.o. for 14 days except the control group.Results: Silymarin treatment decreased the levels of lactate dehydrogenase, creatine kinase isoenzyme MB, alanine aminotransferase and aspartate aminotransferase significantly (p 0.05). In addition, the increase of malondialdehyde level and decrease of glutathione level by valproic acid were significantly suppressed by silymarin in heart tissue (p 0.05). Histologically, the amount of heart injury was significantly lower in valproic acid + silymarin group and histopathological findings were decreased in valproic acid + silymarin group compared to valproic acid group (p 0.005).Conclusion: In this study, it was observed that silymarin has a curative effect on valproic acid induced heart damage. In this sense, we believe that our study will be usefull for other studies which will be study with silymarin and valproic acid.

Combination of Broccoli Sprout Extract and Zinc Provides Better Protection against Intermittent Hypoxia-Induced Cardiomyopathy Than Monotherapy in Mice.

Nuclear factor-E2-related factor 2 (Nrf2) and metallothionein have each been reported to protect against chronic intermittent hypoxia- (IH-) induced cardiomyopathy. Sulforaphane-rich broccoli sprout extract (BSE) and zinc can effectively induce Nrf2 and metallothionein, respectively, to protect against IH-induced cardiomyopathy via antioxidative stress. However, whether the cardiac protective effects of the combination of BSE and zinc can be synergistic or the same has not been evaluated. In this study, we treated 8-week-old C57BL/6J mice with BSE and/or zinc during exposure to IH for 8 weeks. Cardiac dysfunction, as determined by echocardiography, and pathological remodeling and abnormalities, including cardiac fibrosis, inflammation, and oxidative damage, examined by histopathology and western blotting, were clearly observed in IH mice but were not significant in IH mice treated with either BSE, zinc, or zinc/BSE. Furthermore, the effects of the combined treatment with BSE and zinc were always greater than those of single treatments. Nrf2 function and metallothionein expression in the heart increased to a greater extent using the combination of BSE and zinc than using BSE or zinc alone. These findings for the first time indicate that the dual activation of Nrf2 and metallothionein by combined treatment with BSE and zinc may be more effective than monotherapy at preventing the development of IH-induced cardiomyopathy.

Cardioprotective effects of high-intensity interval training are mediated through microRNA regulation of mitochondrial and oxidative stress pathways.

Human studies have shown high-intensity interval training (HIIT) has beneficial cardiovascular effects and is typically more time-efficient compared with traditional endurance exercise. The main goal of this study is to show the potential molecular and functional cardiovascular benefits of HIIT compared with endurance training (ET). Three groups of mice were used including sedentary-control, ET mice, and HIIT mice groups. Results indicated ejection fraction was increased in HIIT compared with ET while fractional shortening was increased in the HIIT group compared with both groups. Blood flow of the abdominal aorta was increased in both exercise groups compared with control. Increases in cross-sectional area and mitochondrial and antioxidative markers in HIIT compared with control were observed, along with several microRNAs. These findings indicate HIIT has specific cardiac-protective effects and may be a viable alternative to traditional ET as a cardiovascular preventative medicine intervention.

Catestatin prevents endothelial inflammation and promotes thrombus resolution in acute pulmonary embolism in mice.

Catestatin (CTS), a catecholamine-release inhibitory peptide, exerts pleiotropic cardiac protective effects. Pulmonary embolism caused by deep vein thrombosis involving vascular dysfunction. The present study aims to investigate the effects of CTS on thrombus formation that may inhibit the development of pulmonary embolism and its potential pathway. Acute pulmonary embolism (APE) model was developed as an in vivo model. The effects of CTS on mice with APE were examined. Human pulmonary artery endothelial cells (HPAECs) were pretreated with CTS before thrombin stimulation, and endothelial inflammation and underlying mechanisms were evaluated in vitro. That plasma CTS level was decreased in APE mice, while the number of platelets was significantly increased. The decreased circulating CTS level negatively associated with the number of platelets. CTS administration increased the survival rate of APE mice and protected against microvascular thrombosis in lung. APE-induced the increase in platelets number and plasma von Willebrand factor (VWF) were inhibited by CTS. Platelets from CTS-treated APE mice showed impaired agonist-induced platelets aggregation and spreading. CTS also ameliorated APE-induced the systemic inflammatory response. In in vivo study, thrombin-induced the increase in inflammation, TLR-4 expression and p38 phosphorylation were abrogated by CTS in HPAECs. Furthermore, TLR-4 overexpression inhibited the effect of CTS on VWF release and inflammation in HPAECs. Collectively, CTS increases thrombus resolution by attenuating endothelial inflammation at partially via inhibiting TLR-4-p38 pathway. The present study may provide a novel approach for anti-thrombosis.

Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-β/Smads pathway.

Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. Astragalus membranaceus (Fisch.) Bunge was widely used in Chinese traditional medicine and showed cardiac protective effects in previous researches. Astragaloside IV(ASG), which is regarded as the most important ingredient of Astragalus, has been showed the effect of cardiac protection via various mechanisms, while no data suggested its action related to miRNAs regulation. The objective of this article is to investigate the inhibition effect of ASG on cardiac fibrosis through the miR-135a-TRPM7-TGF-β/Smads pathway. We extracted the active components from herb according to the paper and measured the content of ASG from the mixture via HPLC. The inhibition potency of cardiac hypertrophy between total extract of Astragalus and ASG was compared. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, ASG (10 mg/kg/d) and Astragalus extract (AE) (4.35 g/kg/d, which contained about ASG 10 mg) were given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 μM) and treated with ASG (10 μM) simultaneously for 24 h. The results showed that both AE and ASG treatment reduced the TRPM7 expression from the gene level and inhibited cardiac fibrosis. ASG group showed similar potency as the AE mixture. ASG treatment significantly decreased the current, mRNA and protein expression of TRPM7 which was one of targets of miR-135a. The activation of TGF-β/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, our results showed that there was a positive feedback between the activation of TGF-β/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis. AE had the effect of cardiac fibrosis inhibition and decreased the mRNA expression of TRPM7. ASG, as one of the effective ingredients of AE, showed the same potency when given the same dose. ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-β/Smads pathway.

Chia (Salvia hispanica L.) – A Potential Crop for Food and Nutrition Security in Africa

There has been an increasing demand for functional foods with numerous health benefits due to intensified consumer awareness leading to a major shift in the consumption patterns of food. This has largely been attributed to increased lifestyle diseases across different populations. The use of food with nutraceutical and functional properties for management of lifestyle diseases like diabetes, obesity, and cardiovascular problems is now gaining momentum among the public. Consequently, the consumption of chia seeds (Salvia hispanica L.) has increased in recent years particularly due to its high content of omega-3 fatty acids and dietary fiber. Chia seeds also contain high quality proteins which offer all the essential amino acids and several vital minerals. In addition, chia seeds are a potential source of antioxidants and polyphenolic compounds such as chlorogenic acid, caffeic acid, myricetin, quercetin, and kaempferol with the major phenolic acid being rosmarinic. Owing to the rich nutritional profile, chia seeds provide numerous health benefits such as; cardiac protective and hepatic protective effects, anti-aging and anti-carcinogenic properties. The high amounts of dietary fibers present in the seeds also confer benefits by preserving good glycemic control thus helps in controlling diabetes mellitus. In addition to the numerous health benefits accrued to consumption of chia seeds, they have great potential in application in the food industry for; development of various baked products, production of biodegradable edible films, use as emulsifiers and stabilizers among other uses. This review provides an in-depth insight into the potential of chia crop in promoting nutrition and food security by providing comprehensive information pertaining to; its origin, cultivation and distribution, physical properties, nutritional characteristics, health benefits, functional properties and its potential use in the food industry. It evident that chia seeds contain superior nutritional components as compared to other seeds and also confers many health benefits such as antioxidative, anti-hypertensive and hypoglycemic properties among others. It possesses physical and functional properties that make it an excellent crop for use in food applications for the development of functional foods. Moreover, its application not only limited to food but can also be used for feed. Chia therefore demonstrates great potential as a crop that can be utilized for improved food and nutrition security.

Histone deacetylase inhibition has cardiac and vascular protective effects in rats with pressure overload cardiac hypertrophy.

Histone deacetylase (HDAC) inhibitors have shown beneficial effects in animal models of cardiovascular diseases. We hypothesized that HDAC inhibitor, sodium valproate (VPA), has cardiac and vascular protective effects in rats with pressure overload cardiac hypertrophy induced by transverse aortic constriction (TAC). Sections of the heart were visualized after hematoxylin and eosin staining, picrosirius red staining and immunohistochemistry. The expression of genes related to cardiac hypertrophy, fibrosis, and oxidative stress was determined by quantitative real-time polymerase chain reaction. The aortic ring tension analysis was conducted using both the ascending aorta and descending thoracic aorta. TAC increased the expression of hypertrophic, fibrotic, and oxidative stress genes, which was attenuated by VPA. In the ascending aorta with intact endothelium, there was a significant decrease in the relaxation response, which was recovered by VPA treatment. These results indicate that VPA has cardiac and vascular protective effects in rats with pressure overload cardiac hypertrophy.

Effect of Selenium Added to the Cardioplegic Solution on Cardiac Protection in Coronary Artery Bypass Grafting Surgeries: A Randomized, Double-Blinded, Clinical Trial Study

Background: Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) triggers an inflammatory reaction, leading to the development of myocardial damage and dysfunction. Selenium is the main cofactor for many antioxidant enzymes. Selenium level is decreased during heart surgeries affecting the cardiopulmonary pump, which in turn can aggravate the organ and heart dysfunction and mortality. Objectives: The aim of this study was to evaluate the cardiac protective effects of adding selenium to cardioplegia solution in these surgeries. Methods: In this randomized, double-blind, clinical trial study that was conducted in the department of cardiac surgery of Shiraz University of Medical Sciences (SUMS) in Shiraz, Iran, 67 elected CABG patients were allocated to the two control or selenium groups. In the intervention group, 1000 μg sodium selenite was added to cardioplegia solution. The same amount of normal saline was added to the cardioplegia solution in the control group. Arterial blood samples were withdrawn before anesthesia induction (T1), immediately after the surgery (T2), as well as, 6 and 24 hours after the surgery (T3 and T4 respectively), to determine the CK-MB and Troponin I levels. Results: According to our findings, the CK-MB and Troponin I cardiac enzyme levels were significantly different, considering different time points (P 0.05). There were also no significant differences between the two groups regarding systolic and diastolic blood pressures. Conclusions: The administration of 1000 µg sodium selenite via cardioplegia solution had no significant cardioprotective effect during coronary bypass surgery in CABG patients.

P3115Effect of calcitriol attenuates doxorubicin-induced cardiac dysfunction in mice model: focus on endothelial-to-mesenchymal transition

Abstract Objective Doxorubicin (DOX) is an effective anti-neoplasm drug, but the early and late cardiac toxicity limits its clinical use. The Endothelial-to-mesenchymal transition (EndMT) has been found to involve in the process of heart failure. It's unclear whether EndMT plays a role in DOX-induced cardiomyopathy (DoIC). Calcitriol is an active form Vitamin D3, which blocks the growth of cancer cells via inhibiting Smad pathway. This study investigated the cardiac protective effect of calcitriol via inhibiting of EndMT in DoIC. Methods/Findings C57BL/6 mice and endothelial-specific labeled mice were administered Dox twice weekly for 4 weeks [intraperitoneally (i.p.), 32 mg/kg cumulative dose]and were subsequently treated with/without calcitriol for 12 weeks. The cardiac echography revealed diastolic dysfunction at 13 weeks following the first DOX treatment and was accompanied by increased of myocardial fibrosis and up-regulated pro-fibrotic proteins.(Figure A-C) Calcitriol attenuated DOX-induced myocardial fibrosis, down-regulated pro-fibrotic proteinsand diastolic function. Endothelial fate tracing revealed that endothelium-derived cells contributed DOX-induced cardiac remodelling through EndMT and Calcitriol attenuated this process without attenuating Dox-induced cardiac myocyte and endothelial cell damage.(Figure D) In vitro, we examined if calcitriol would inhibit EndMT and fibroblast-to-myofibroblast transition (FMT) through the Smad pathway. Human umbilical vein endothelial cells (HUVECs) and mouse cardiac fibroblasts were treated with TGF-beta with or without calcitriol. Morphological, immunofluorescence staining, and western blot analyses were carried out to evaluate EndMT and FMT. Calcitriol attenuated EndMT and FMT by inhibiting the Smad2 pathway. Taken together, calcitriol didn't reduced Doxorubicin induced damage of cardiomocyte and endothelial cells. But calcitriol inhibit doxorubicin induced heart failure by attenuating cardiac fibrosis through inhibiting Smad pathway. Conclusion Calcitriol attenuated DOX-induced cardiomyopathy partial through inhibiting EndMT process. Acknowledgement/Funding CMRPG8E0661-3

Role of cardiac progenitor cell-derived exosome-mediated microRNA-210 in cardiovascular disease.

Cardiac progenitor cells are considered to be one of the most promising stem cells for heart regeneration and repair. The cardiac protective effect of CPCs is mainly achieved by reducing tissue damage and/or promoting tissue repair through a paracrine mechanism. Exosome is a factor that plays a major role in the paracrine effect of CPCs. By delivering microRNAs to target cells and regulating their functions, exosomes have shown significant beneficial effects in slowing down cardiac injury and promoting cardiac repair. Among them, miRNA‐210 is an important anoxic‐related miRNA derived from CPCs exosomes, which has great cardiac protective effect of inhibiting myocardial cell apoptosis, promoting angiogenesis and improving cardiac function. In addition, circulating miR‐210 may be a useful biomarker for the prediction or diagnosis of related cardiovascular diseases. In this review, we briefly reviewed the mechanism of miR‐210 derived from CPCs exosomes in cardiac protection in recent years.