Cardiac Dysfunction In Rats Research Articles

A new natural product derived from cyclosorus terminans provides cardiometabolic protection against obese-induced cardiac dysfunction in rats via suppressing mitochondrial dysfunctions and apoptosis

Abstract Background The development of a novel pharmacological target for obesity has long been considered challenging in mitigating the global cardiovascular complications and mortality. Given the cytotoxic effects associated with various anti-obesity drugs, there is growing interest in exploring new natural products as potential sources for bioactive agents to treat obesity-associated diseases with minimal side effects. While Cyclosorus terminans extract has demonstrated anti-diabetic and anti-obese efficacies in adipose-derived stem cells, its cardioprotective effects in high-fat diet (HFD)-induced obese-insulin resistance rat models have never been elucidated. Purpose To examine the effects of long-term Cyclosorus terminans treatment on metabolic, cardiac, and mitochondrial functions and apoptosis in HFD-induced obese-insulin-resistant rat models Methods Male Wistar rats (n=10) were continually fed with HFD and treated with either vehicle (HFV, virgin oil for 2 ml/kg/day, p.o., n=5) or Cyclosorus terminans (HFC, 100 mg/kg/day, p.o., n=5) for 12 weeks. Rats fed a normal diet (NDV, n=5) were used as a control to confirm the development of HFD-induced obesity. The left ventricular ejection fraction (LVEF) and the ratio between early (E) and late atrial (A) ventricular filling velocity were measured using echocardiography, and the homeostatic model assessment for insulin resistance (HOMA-IR) was determined using blood serum. The cardiac tissue was processed to assess mitochondrial reactive oxygen species (ROS) levels, membrane potential (MMP) changes via red/green fluorescence intensity ratio, and apoptotic protein. Results HFV rats became obese and had impaired cardiometabolic function as shown by reducing LVEF, E/A ratio, and increasing HOMA-IR, respectively (Fig. 1A-C). These obese rats also had mitochondrial ROS overproduction, MMP depolarization (reduced red/green ratio), and apoptosis (increased Bax protein expression) (Fig. 1D-F). Treatment with Cyclosorus terminans (HFC) significantly mitigated mitochondrial dysfunction and apoptosis, resulting in cardiometabolic protection in HFD-fed rats (Fig. 1A-F). Conclusion A new natural product derived from Cyclosorus terminans effectively protected the heart against long-term HFD-induced cardiometabolic impairments by reducing mitochondrial dysfunction and apoptosis. These findings demonstrate Cyclosorus terminans as a novel cardiometabolic protection against obesity-related cardiac complications.

GPER Stimulation Attenuates Cardiac Dysfunction in a Rat Model of Preeclampsia.

Preeclampsia poses a substantial clinical challenge, characterized by maternal hypertension, cardiac dysfunction, and persistent cardiovascular risks for both the mother and offspring. Despite the known roles of the estrogen receptor (GPER [G protein-coupled estrogen receptor]) in placental development, its impact on cardiovascular aspects within a preeclampsia animal model remains unexplored. We propose that G-1, a GPER agonist, could have the potential to regulate not only hypertension but also cardiac dysfunction in rats with preeclampsia. To explore the influence of G-1 on preeclampsia, we used the reduced uterine perfusion pressure (RUPP) model. RUPP rats were administered either G-1 (100 µg/kg per day) or hydralazine (25 mg/kg per day). We conducted echocardiography to probe the intricate cardiac effects of G-1. The RUPP rat model revealed signs of hypertension and cardiac dysfunction and alterations in gene and protein expression within placental and heart tissues. G-1 treatment reduced blood pressure and reversed cardiac dysfunction in rats with preeclampsia. In contrast, administration of the vasodilator hydralazine reduced blood pressure without an improvement in cardiac function. In addition, while G-1 treatment restored the levels of sFLT-1 (soluble fms-like tyrosine kinase-1) in RUPP rats, hydralazine did not normalize this antiangiogenic factor. The therapeutic intervention of G-1 significantly mitigated the cardiovascular dysfunction observed in the RUPP rat model of preeclampsia. This discovery underscores the broader significance of understanding GPER's role in the context of preeclampsia-related cardiovascular complications.

Cardioprotective Potentials of Anacardium occidentale Nuts Methanolic Extract in Diabetes-Induced Cardiac Dysfunction in Rats

Background: The unwanted adverse toxicity displayed by synthetic antidiabetic medicine leads to the search for effective natural medicine to combat diabetes complications. This study investigated the cardioprotective of Anacardium occidentale nuts methanolic in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Materials and methods: Forty male adult Wistar were used and fed with HFD for 6 weeks before diabetes induction. The rats were grouped into 5 groups, 8 rats/group. Group I: normal control; Group II: diabetic control; Group III & IV: diabetic rats + 100 mg/kgb.wt & 200 mg/kgb.wt Anacardium occidentale nuts methanolic extract; Group V: diabetic rats + 200 mg/kgb.wt metformin. The rats were sacrificed on the experiment’s last day, blood samples were collected and the hearts were isolated for biochemical parameters estimation. Results: Food intake, water intake, plasmas insulin, Fasting Blood Glucose (FBG), glycosylated hemoglobin (HbA1c), cardiac enzymes, lipid profile, inflammatory cytokines, malondialdehyde, fibrotic marker, caspase-3 in cardiac of diabetic rats were elevated (p < 0.05) significantly. Body weight, cardiac antioxidant, and anti-apoptotic marker levels diminished (p < 0.05) significantly in diabetic rats. 100 mg/kgb.wt & 200 mg/kgb.wt of Anacardium occidentale nuts methanolic extract administration significantly suppressed the plasma insulin, FBG, HbA1c, cardiac lipid profile, cardiac enzymes biomarker, cardiac inflammatory cytokines, cardiac malondialdehyde, cardiac fibrotic marker, cardiac caspase-3, food intake & water intake and increased the body weight, cardiac antioxidant & cardiac anti-apoptotic marker in the diabetic rats. Conclusion: Anacardium occidentale nuts attenuate cardiac injury in diabetes. It could be a natural medicine to manage diabetes-cardiovascular complications.

Fennel seeds extract prevents fructose-induced cardiac dysfunction in a rat model of metabolic syndrome via targeting abdominal obesity, hyperuricemia and NF-κβ inflammatory pathway

BackgroundMetabolic syndrome (MetS) is commonly associated with increased risk of cardiac disease that affects a large number of world populations. ObjectiveThis research attempted to investigate the efficacy of fennel seeds extract (FSE) in preventing development of cardiac dysfunction in rats on fructose enriched diet for 3 months, as a model of MetS. Materials & methodsThirty adult Wistar male rats (160–170 g) were assigned into 5 groups including control, vehicle, FSE (200 mg/kg BW) and fructose (60%) fed rats with and without FSE. Following the last treatment, blood pressure, ECG and heart rate were measured. Next, blood and cardiac tissues were taken for biochemical and histological investigations. ResultsFeeding fructose exhibited characteristic features of MetS involving, hypertension, abnormal ECG, elevated heart rate, serum glucose, insulin, lipids and insulin resistance, accompanied by abdominal obesity, cardiac hypertrophy and hyperuricemia. Fructose fed rats also showed significant reduction in cardiac antioxidants (GSH, SOD, CAT) with elevation in oxidative stress indices (NADPH oxidase, O2.-, H2O2, MDA, PCO), NF-κβ, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), adhesion molecules (ICAM-1, VCAM-1) and serum cardiac biomarkers (AST, LDH, CK-MB, cTn-I). Histopathological changes evidenced by destruction of cardiac myofibrils, cytoplasmic vacuolization, and aggregation of inflammatory cells were also detected. Consumption of FSE showed high ability to alleviate fructose-induced hypertension, ECG abnormalities, cardiac hypertrophy, metabolic alterations, oxidative stress, inflammation and histological injury. ConclusionFindings could suggest FSE as a complementary supplement for preventing MetS and associated cardiac outcomes. However, well controlled clinical studies are still needed.

Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by Pistacia atlantica in diabetes-induced cardiac dysfunction in rat

Preparation, characterization, and determination of the therapeutic effects of copper nanoparticles green-formulated by <i>Pistacia atlantica</i> in diabetes-induced cardiac dysfunction in rat

Pretreatment with Indole-3-Propionic Acid Attenuates Lipopolysaccharide-Induced Cardiac Dysfunction and Inflammation Through the AhR/NF-κB/NLRP3 Pathway.

Patients with sepsis frequently develop septic cardiomyopathy, which is known to be closely related to excessive inflammatory responses. Indole-3-propionic acid (IPA) is a tryptophan metabolite with anti-inflammatory properties that have been demonstrated in various studies. In this study, we investigated the underlying mechanisms and therapeutic role of IPA in septic cardiomyopathy. To investigate the role of IPA in septic cardiomyopathy, we constructed a lipopolysaccharide (LPS)-induced rat model of septic cardiomyopathy, and treated rats with IPA. Inflammatory factors and the NF-κB/NLRP3 pathway were evaluated in myocardial tissues and cells after IPA treatment using RT-qPCR, ELISA, Western blotting, and immunohistochemistry. To further elucidate the role of the aryl hydrocarbon receptor (AhR), we detected changes in inflammatory mediators and the NF-κB/NLRP3 pathway in in vivo and in vitro models of septic cardiomyopathy, which were treated with the AhR antagonist CH-223191 and/or AhR agonist FICZ. IPA supplementation improved cardiac dysfunction in rats with septic cardiomyopathy. IPA reduced inflammatory cytokine release and inhibited NF-κB/NLRP3 signaling pathway in myocardial tissue and in H9c2 cells. CH-223191 impaired the anti-inflammatory effect of IPA in LPS-treated cells, whereas FICZ exerted the same effect as IPA. IPA also exhibited anti-inflammatory activity by binding to the AhR. Our results indicated that IPA attenuated septic cardiomyopathy in rats via AhR/NF-κB/NLRP3 signaling. Our study revealed that IPA improved left heart dysfunction and myocardial inflammation caused by sepsis via AhR/NF-κB/NLRP3 signaling, suggesting that IPA is a potential therapy for septic cardiomyopathy.

Pinostrobin attenuated cadmium instigated cardiotoxicity in albino rats: A biochemical, inflammatory, apoptotic and histopathological examination

Cadmium (Cd) is a noxious and non-biodegradable heavy metal which instigates various organ toxicities such as cardiac injuries. Pinostrobin (PSB) is a potent dietary bioflavonoid, which shows various pharmacological potentials. The current research was designed to evaluate the ameliorative effects of PSB against Cd elicited cardiac dysfunction in rats. Twenty-four albino rats were apportioned into four equal groups viz. control, Cd (5 mg/kg), Cd (5 mg/kg) + PSB (40 mg/kg) and PSB (40 mg/kg) only treated group. It was observed that Cd intoxication reduced catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), glutathione peroxidase (GPx), activities and glutathione S-transferase (GST) contents while escalating the levels of reactive oxygen species (ROS), hydrogen peroxide (H2O2) and malondialdehyde (MDA). Furthermore, Cd exposure escalated the levels of cardiac injury markers such as creatine phosphokinase (CPK), creatine kinase-myocardial band (CK-MB), troponin I and lactate dehydrogenase (LDH). Besides, the levels of inflammatory cytokines nuclear factor- κB (NF-κB), interleukin 1beta (IL-1ß), tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity were upregulated in Cd intoxicated group. Similarly, Caspase-3, Bax and Caspase-9 levels were augmented, and Bcl-2 levels were reduced after Cd administration. In addition, the histopathological examination revealed a notable cardiac tissue impairment in the Cd exposed group. Nonetheless, PSB treatment significantly (p < 0.05) recovered the abovementioned Cd-induced impairments. Therefore, the current study revealed that PSB might be a promising ameliorative agent to ameliorate Cd instigated cardiac damages.

Evaluation of the protective effect of salidroside on arsenic-induced cardiac dysfunction in rats.

Evaluation of the protective effect of salidroside on arsenic-induced cardiac dysfunction in rats.

Moderate- and High-Intensity Endurance Training Alleviate Diabetes-Induced Cardiac Dysfunction in Rats.

Exercise training is an encouraging approach to treat cardiac dysfunction in type 2 diabetes (T2DM), but the impact of its intensity is not understood. We aim to investigate whether and, if so, how moderate-intensity training (MIT) and high-intensity interval training (HIIT) alleviate adverse cardiac remodeling and dysfunction in rats with T2DM. Male rats received standard chow (n = 10) or Western diet (WD) to induce T2DM. Hereafter, WD rats were subjected to a 12-week sedentary lifestyle (n = 8), running MIT (n = 7) or HIIT (n = 7). Insulin resistance and glucose tolerance were assessed during the oral glucose tolerance test. Plasma advanced glycation end-products (AGEs) were evaluated. Echocardiography and hemodynamic measurements evaluated cardiac function. Underlying cardiac mechanisms were investigated by histology, western blot and colorimetry. We found that MIT and HIIT lowered insulin resistance and blood glucose levels compared to sedentary WD rats. MIT decreased harmful plasma AGE levels. In the heart, MIT and HIIT lowered end-diastolic pressure, left ventricular wall thickness and interstitial collagen deposition. Cardiac citrate synthase activity, mitochondrial oxidative capacity marker, raised after both exercise training modalities. We conclude that MIT and HIIT are effective in alleviating diastolic dysfunction and pathological cardiac remodeling in T2DM, by lowering fibrosis and optimizing mitochondrial capacity.

Abstract P205: G Protein-Coupled Estrogen Receptor Stimulation Attenuates Hypertension And Cardiac Dysfunction In The Reduced Uterine Perfusion Pressure Model Of Preeclampsia

Preeclampsia (PE) is a disorder of pregnancy associated with maternal hypertension and cardiac dysfunction. Women with a history of PE have increased risk of cardiovascular disease and mortality that persist well beyond the post-partum period. Evidence suggests that the new estrogen receptor (GPER) is a beneficial regulator of placental development. Other studies have shown the role of GPER in promoting vasodilation and cardioprotection. However, the cardiovascular effects of GPER in an animal model of PE have not yet been determined. Thus, we hypothesize that the activation of GPER by its selective agonist G-1 is associated with the regulation of hypertension and cardiac dysfunction in rats following placental insufficiency. The reduced uterine perfusion pressure (RUPP) model was used to induce placental insufficiency in the dam by placing silver clips on abdominal aorta and uterine arteries on gestational day (GD) 14 of a 19-day gestation. RUPP rats received G-1 (100 μg/kg/day) or vehicle subcutaneously by osmotic minipump. Echocardiography was performed on GD18 to assess the effectiveness of G-1 on heart function in PE dams. On GD19, rats had carotid catheters placed, and hemodynamic measurements were made. RUPP rats exhibited hypertension and cardiac alterations, including global myocardial motion dyssynchrony, and reduced left ventricular systolic and diastolic function when compared with SHAM animals. G-1 treatment significantly attenuated hypertension and cardiac functional aberrations caused by PE in RUPP rats, a finding that may have important implications for the ongoing clinical evaluations of new drugs for the treatment of PE and its comorbidities.

Dapagliflozin attenuates cardiac remodeling and dysfunction in rats with β-adrenergic receptor overactivation through restoring calcium handling and suppressing cardiomyocyte apoptosis.

Background: Long-term β-adrenergic receptor (β-AR) activation can impair myocardial structure and function. Dapagliflozin (DAPA) has been reported to improve clinical prognosis in heart failure patients, whereas the exact mechanism remains unclear. Here, we investigated the effects of DAPA against β-AR overactivation toxicity and explored the underlying mechanism.Methods and Results: Rats were randomized to receive saline + placebo, isoproterenol (ISO, 5mg/kg/day, intraperitoneally) + placebo, or ISO + DAPA (1mg/kg/day, intragastrically) for 2-week. DAPA treatment improved cardiac function, alleviated myocardial fibrosis, prevented cardiomyocytes (CMs) apoptosis, and decreased the expression of ER stress-mediated apoptosis markers in ISO-treated hearts. In isolated CMs, 2-week ISO stimulation resulted in deteriorated kinetics of cellular contraction and relaxation, increased diastolic intracellular Ca2+ level and decay time constant of Ca2+ transient (CaT) but decreased CaT amplitude and sarcoplasmic reticulum (SR) Ca2+ level. However, DAPA treatment prevented abnormal Ca2+ handling and contractile dysfunction in CMs from ISO-treated hearts. Consistently, DAPA treatment upregulated the expression of SR Ca2+-ATPase protein and ryanodine receptor 2 (RyR2) but reduced the expression of phosphorylated-RyR2, Ca2+/calmodulin-dependent protein kinase II (CaMKII), and phosphorylated-CaMKII in ventricles from ISO-treated rats.Conclusion: DAPA prevented myocardial remodeling and cardiac dysfunction in rats with β-AR overactivation via restoring calcium handling and suppressing ER stress-related CMs apoptosis.

Effect of Dendrobine on Cardiac Dysfunction in Rats with Myocardial Infarction by Regulating Autophagy

Aim: To observe Dendrobine (Den) on rats with post-myocardial infarction cardiac dysfunction and mechanism. Materials: Dividing 27 rats as Sham, Model and Den groups, rats treated with two weeks of drug had their cardiac function and structure measured by ultrasound; their myocardial pathological changes observed by HE and Masson staining and observe apoptosis cell number by TUNEL staining; their serum activities of LDH and CK-MB detected by ELISA; myocardial autophagy protein expressions detected by WB and immunohistochemistry. Results: Model group displayed decreased cardiac function levels, enlarged area of myocardial fibrosis, more serum activities of LDH and CK-MB, increased myocardial tissue structural damage and apoptosis cell number, downregulated LAMP2 expression, and up-regulated expressions of Beclin1, LC3-II/LC3-I rate, and P62. To rat victims of myocardial infarction, Den improved cardiac function, reduced area of myocardial fibrosis, compromised activities of serum LDH and CK-MB, and relieved damage in myocardial structure, decreased apoptosis cell number in myocardial tissue, up-regulated the expressions of Beclin1, LAMP2 and LC3-II, and down-regulated P62 to promote the autophagy in myocardium damaged by myocardial infarction. Conclusion: Den alleviates post-myocardial infarction cardiac dysfunction through improvement of autophagosomes formation and autophagic flux via Beclin1/LAMP2 pathway.

Effects of Psidium guajava and Ribes americanum Aqueous Extracts and Dietary Modification on some Markers of Renal, Cardiac Dysfunction in Rats

The effect of aqueous extract of P. guajava and R. americanum and dietary modification interactions on serum renal function markers levels (urea, creatinine) cardiac function markers (lactate dehydrogenase, creatinine kinase), serum ions (calcium, sodium, and potassium ions) were investigated in rats. Fully grown Wister strain rats were exposed to high fat and salted diet formulation and treated with the aqueous extract for a period of 6 weeks. The diets were formulated by adding 25% animal fat and 5% palm oil to standard feeds (Vital feeds, Bukuru Jos, Plateau. Significant decrease in serum urea, creatinine, and lactate dehydrogenase and creatine kinase activities in the group treated with P. guajava and R. americanum aqueous extract compared to the high fat-salted water group. There was no significant difference in plasma urea and Creatinine, LDH and CK levels between the standard feeds and standard feed plus salted water group. Significant increase in the plasma Creatinine and lactate dehydrogenase levels (at p&lt;0.05) of the high-fat plus salted water group when compared with the high fat group. Significant (at p&lt;0.05) increase in serum sodium of the group exposed to salted water when compared with the non-salted water group. There was a significant (p&lt;0.05) decrease in serum sodium levels of extract administered groups compared to the high fat-salted water and standard feed salted water groups. There was also a significant increase, at p&lt;0.05, in serum potassium and calcium of the extracts administered group when compared with the standard feed salted water, high fat and high fat salted water groups. The study showed that the combined effects of high fat and high salt increased serum sodium and decreased serum potassium and calcium. Administration of the aqueous extract administration reversed by the effects

Brain Interleukin-17A contributes to neuroinflammation and cardiac dysfunction in rats with myocardial infarction.

Proinflammatory cytokines produced outside the central nervous system can act in the brain to promote sympathetic activation that contributes to the progression of heart failure (HF). Interleukin (IL)-17A, a key inflammatory regulator which orchestrates immune responses to promote chronic inflammation, has been implicated in the pathophysiology of HF. We previously reported that IL-17A acts within the brain, particularly in the hypothalamic paraventricular nucleus (PVN), to increase expression of inflammatory mediators and, consequently, sympathetic outflow. The present study sought to determine whether IL-17A levels are elevated in a rat model of HF induced by myocardial infarction and, if so, whether increased expression of IL-17A in the brain itself contributes to neuroinflammation and cardiac dysfunction in this disease setting. Male SD rats underwent coronary artery ligation (CL) to induce HF or sham operation (SHAM). Compared with SHAM rats, HF rats exhibited significantly increased IL-17A levels in plasma, beginning within 1 week with a peak increase at 4 weeks after CL. IL-17A levels in cerebrospinal fluid (CSF) were also increased in HF rats and correlated with IL-17A levels in the plasma. The mRNA expression of IL-17A and its receptor IL-17RA, but not IL-17RC, was markedly upregulated in the PVN of HF when compared with SHAM rats. Genetic knockdown of IL-17RA by bilateral PVN microinjections of an IL-17RA siRNA AAV virus attenuated mRNA expression of proinflammatory cytokines and chemokines, and ameliorated sympathetic activation and cardiac function in HF rats. These data indicate that elevated expression of IL-17A in the brain in HF contributes to the excessive central inflammatory state and cardiac dysfunction in HF. Interventions to suppress IL-17A/IL-17RA axis in the brain have the potential for treating HF.

Preparation, chemical characterization and determination of the antioxidant, cytotoxicity and therapeutic effects of gold nanoparticles green-synthesized by Calendula officinalis flower extract in diabetes-induced cardiac dysfunction in rat

• Preparation of mono-dispersed gold nanoparticles using the aqueous extract of Calendula officinalis. • Calendula officinalis acted as reducing and stabilizing agent. • COE@AuNPs shown good antioxidant properties. • The results shown therapeutic effects of COE@AuNPs on diabetes-induced cardiac dysfunction in rat. An ultrasound promoted bio-inspired synthesis of mono-dispersed Au nanoparticles (NPs) has been adopted in this article, templated over Calendula officinalis flower extract. The phytochemicals therein were explored as natural and green reducing as well as NP stabilizers. The as-synthesized bio-nanomaterial (COE@AuNPs) was characterized over FT-IR, UV–Vis spectroscopy, TEM, FE-SEM, EDX and XRD studies. Due to plant extract-based synthesis, the material was obtained as highly dispersed, semi-spherical particles of minuscule dimension (20–25 nm). In the in vivo condition, diabetes was induced by a fructose-enriched diet supplemented by streptozotocin. Half of the animals received COE@AuNPs by oral gavage. Compared to the animals receiving standard chow, serum fasting glucose level was increased and glucose tolerance was diminished in diabetic rats. COE@AuNPs affect significantly fasting hyperglycemia and glucose intolerance; also, it attenuated the diabetes-induced deterioration of cardiac output and cardiac work. Moreover, COE@AuNPs prevented the diabetes-induced increase in cardiac STAT3 phosphorylation. The results of this study indicated the therapeutic effects of COE@AuNPs the diabetes-induced cardiac dysfunction in rat.

Lithium Treatment Improves Cardiac Dysfunction in Rats Deprived of Rapid Eye Movement Sleep.

Rapid eye movement (REM) sleep deprivation triggers mania and induces cardiac fibrosis. Beyond neuroprotection, lithium has cardioprotective potential and antifibrotic activity. This study investigated whether lithium improved REM sleep deprivation-induced cardiac dysfunction and evaluated the potential mechanisms. Transthoracic echocardiography, histopathological analysis, and Western blot analysis were performed in control and REM sleep-deprived rats with or without lithium treatment (LiCl of 1 mmol/kg/day administered by oral gavage for 4 weeks) in vivo and in isolated ventricular preparations. The results revealed that REM sleep-deprived rats exhibited impaired contractility and greater fibrosis than control and lithium-treated REM sleep-deprived rats. Western blot analysis showed that REM sleep-deprived hearts had higher expression levels of transforming growth factor beta (TGF-β), phosphorylated Smad 2/3, and alpha-smooth muscle actin than lithium-treated REM sleep-deprived and control hearts. Moreover, lithium-treated REM sleep-deprived hearts had lower expression of angiotensin II type 1 receptor, phosphorylated nuclear factor kappa B p65, calcium release-activated calcium channel protein 1, transient receptor potential canonical (TRPC) 1, and TRPC3 than REM sleep-deprived hearts. The findings suggest that lithium attenuates REM sleep deprivation-induced cardiac fibrogenesis and dysfunction possibly through the downregulation of TGF-β, angiotensin II, and Ca2+ signaling.

Abstract P2042: Down-regulation Of Microrna-16 Improved Selenium Deficiency-induced Cardiac Dysfunction In Rats Through Wnt/β-catenin Signaling

Objective: To investigate the mechanisms and effects of down-regulation of microRNA-16 in selenium deficiency-induced cardiac dysfunction in rats. Methods: Selenium deficiency was induced by low selenium diet. Injection of AAV9-carried microRNA-16 interference was used to down-regulate microRNA-16. Cardiac functions were evaluated by echocardiography and serum BNP concentrations. The expression of microRNA-16 was examined by RT-PCR. Expression levels of wnt, β-catenin, c-myc and caspase-3 were evaluated by Western blotting. Results: Down-regulation of microRNA-16 in rats with selenium deficiency significantly improved cardiac functions. Meanwhile, the down-regulation of microRNA-16 reduced the expression of wnt1, β-catenin and TCF in the Wnt/β-catenin signaling pathway, and the expression of c-myc and caspase-3 were also decreased. Conclusions: The down-regulation of microRNA-16 can improve the cardiac function of rats with selenium deficiency via the inactivation of Wnt/β-catenin signaling pathway.

Involvement of ET-1/eNOS in the ameliorating effect of electroacupuncture on cardiac dysfunction in rats with spontaneously hypertensive

To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function of ventriculus sinister in rats with spontaneously hypertensive (SHR), and to explore the mediation effect of endothelin-1 (ET-1)/endothelial nitric oxide synthase (eNOS). Six 12-week-old male Wistar Kyoto (WKY) rats were taken as the normal group. Eighteen 12-week-old SHR were randomly divided into a model group, an EA group and a sham EA group, 6 rats in each group. The rats in the EA group were treated with EA (disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity) at "Neiguan" (PC 6), 30 min each time, once a day for 8 weeks. The rats in the sham EA group were treated with superficial needling at "Neiguan" (PC 6) with no electrical stimulation applied. After treatment, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were tested by echocardiographic analysis. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR), the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected. The serum content of ET-1 was detected by ELISA. Western blot was used to evaluate the expression of ETAR, eNOS in myocardial tissue of left ventricular. Compared with the normal group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were decreased (P<0.01, P<0.05), while LVSP, LVEDP, +dp/dtmax and -dp/dtmax were increased (P<0.01) in the model group. Compared with the model group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were increased (P<0.01, P<0.05), and LVSP and LVEDP were decreased (P<0.01) in the EA group. Compared with the normal group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were increased (P<0.01), whereas expression of eNOS was decreased (P<0.01) in the model group. Compared with the model group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were decreased (P<0.05), whereas expression of eNOS was increased (P<0.05) in the EA group. EA intervention may alleviate hypertensive cardiac function damage by up-regulating the expression of eNOS protein in myocardial tissue, down-regulating the serum content of ET-1 and the expression of ETAR protein in myocardial tissue.

Paricalcitol Attenuates Metabolic Syndrome-Associated Heart Failure through Enhanced Mitochondrial Fusion.

Objectives Transition from cardiac hypertrophy to failure involves adverse metabolic reprogramming involving mitochondrial dysfunction. We have earlier shown that vitamin D deficiency induces heart failure, at least in part, through insulin resistance. However, whether activation of vitamin D receptor (VDR) can attenuate heart failure and underlying metabolic phenotype requires investigation. Thus, we aimed to assess the cardioprotective potential of paricalcitol, a vitamin D receptor-activator, against cardiac hypertrophy and failure in high-fat high-fructose-fed rats. Methods Male Sprague Dawley rats were fed control (Con) or high-fat high-fructose (HFHFrD) diet for 20 weeks. After 12 weeks, rats from HFHFrD group were divided into the following: HFHFrD, HFHFrD+P (paricalcitol i.p. 0.08 μg/kg/day) and HFHFrD+E (enalapril maleate i.p. 10 mg/kg/day). Intraperitoneal glucose tolerance test, blood pressure measurement, and 2D echocardiography were performed. Cardiac fibrosis was assessed by Masson's trichrome staining of paraffin-embedded heart sections. Mitochondrial DNA and proteins, and citrate synthase activity were measured in rat hearts. VDR was silenced in H9c2 cardiomyoblasts, and immunoblotting was performed. Results Paricalcitol improved glucose tolerance, serum lipid profile, and blood pressure in high-fat high-fructose-fed rats. Paricalcitol reduced cardiac wall thickness and increased ejection fraction in high-fat high-fructose-fed rats but had no effect on perivascular fibrosis. PGC1-α was upregulated in the HFHFrD+P group compared to the HFHFrD group, but there was no significant difference in mitochondrial content. Citrate synthase activity was significantly higher in the HFHFrD+P group compared to the HFHFrD group. Rat hearts of the HFHFrD+P group had significantly higher expression of mitofusins. H9c2 cells with VDR knockdown showed significantly lower expression of Mfn2. Improvement in the HFHFrD+P group was comparable with that in the HFHFrD+E group. Conclusions Paricalcitol reverses cardiac dysfunction in rats with metabolic syndrome by enhancing mitochondrial fusion. We demonstrate repurposing potential of the drug currently used in end-stage kidney disease.

Inhibition of miRNA-1-Mediated Inflammation and Autophagy by Astragaloside IV Improves Lipopolysaccharide-Induced Cardiac Dysfunction in Rats.

IntroductionAstragaloside IV (AS-IV) is one of the main active components isolated from the traditional Chinese medicinal herb, Astragalus membranaceus. The present study was designed to investigate whether the regulation of microRNA-1 (miR-1)-mediated inflammation and autophagy contributes to the protective effect of AS-IV against cardiac dysfunction in rats treated with lipopolysaccharides (LPS).MethodsAnimal model of cardiac dysfunction in rats or cellular model of injured H9c2 heart cell line was established by using LPS. Echocardiography, electron microscopy, enzyme-linked immunosorbent assay, immunofluorescence, quantitative RT-PCR, and Western blotting were used to determine the cardiac function and expression of inflammation- and autophagy-related proteins at both the mRNA and protein levels.ResultsLPS caused cardiac dysfunction in rats or injury in H9c2 cells and induced inflammation and autophagy. Compared with LPS treatment, AS-IV treatment attenuated cardiac dysfunction or cell injury, accompanied by inhibition of inflammation and autophagy. However, the miR-1 mimics partly abolished the effects of AS-IV. In addition, the effect of the miR-1 inhibitor was similar to that of AS-IV in the LPS model. Further analyses showed that AS-IV treatment decreased the mRNA expression of miR-1 in the heart tissue of rats and H9c2 cells treated with LPS.ConclusionThese results suggest that AS-IV attenuated cardiac dysfunction caused by LPS by inhibiting miR-1-mediated inflammation and autophagy, thereby providing a novel mechanism for the protection against cardiac diseases.