curcumin and Heart-Failure

Cardiac fibrosis stems from the changes in the expression of fibrotic genes in cardiac fibroblasts (CFs) in response to the tissue damage induced by various cardiovascular diseases (CVDs) leading to their transformation into active myofibroblasts, which produce high amounts of extracellular matrix (ECM) proteins leading, in turn, to excessive deposition of ECM in cardiac tissue. The excessive accumulation of ECM elements causes heart stiffness, tissue scarring, electrical conduction disruption and finally cardiac dysfunction and heart failure. Curcumin (Cur; also known as diferuloylmethane) is a polyphenol compound extracted from rhizomes of Curcuma longa with an influence on an extensive spectrum of biological phenomena including cell proliferation, differentiation, inflammation, pathogenesis, chemoprevention, apoptosis, angiogenesis and cardiac pathological changes. Cumulative evidence has suggested a beneficial role for Cur in improving disrupted cardiac function developed by cardiac fibrosis by establishing a balance between degradation and synthesis of ECM components. There are various molecular mechanisms contributing to the development of cardiac fibrosis. We presented a review of Cur effects on cardiac fibrosis and the discovered underlying mechanisms by them Cur interact to establish its cardio-protective effects.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Differentiation; Curcumin; Fibrosis; Heart Failure; Humans; Myocardium; Myofibroblasts; Signal Transduction

Numerous studies document an increased production of reactive oxygen species (ROS) with a subsequent decrease in nitric oxide (NO) bioavailability in different cardiovascular diseases, including hypertension, atherosclerosis, and heart failure. Many natural polyphenols have been demonstrated to decrease ROS generation and/or to induce the endogenous antioxidant enzymatic defense system. Moreover, different polyphenolic compounds have the ability to increase the activity/expression of endothelial nitric oxide synthase (eNOS) with a subsequent enhancement of NO generation. However, as a result of low absorption and bioavailability of natural polyphenols, the beneficial effects of these substances are very limited. Recent progress in delivering polyphenols to the targeted tissues revealed new possibilities for the use of polymeric nanoparticles in increasing the efficiency and reducing the degradability of natural polyphenols. This review focuses on the effects of different natural polyphenolic substances, especially resveratrol, quercetin, curcumin, and cherry extracts, and their ability to bind to polymeric nanoparticles, and summarizes the effects of polyphenol-loaded nanoparticles, mainly in the cardiovascular system.

Topics: Animals; Antioxidants; Atherosclerosis; Biological Availability; Biological Products; Cardiovascular System; Curcumin; Drug Compounding; Heart Failure; Humans; Hypertension; Nanocapsules; Nitric Oxide; Nitric Oxide Synthase Type III; Polymers; Polyphenols; Quercetin; Reactive Oxygen Species; Resveratrol

Chronic heart failure is the final stage of such heart diseases as hypertension, cardiomyopathy, and myocardial infarction. Since the incidence of heart failure has increased in recent decades, heart failure is now a major public health problem in developed countries, including Japan. Recently, some studies have demonstrated that natural products, used as nutritional supplements, play an important role in preventing the development of heart failure in animal studies. In our previous study, we showed that curcumin, a natural polyphenol compound derived from Curcuma longa, exhibits therapeutic potency against heart failure. To establish the pharmacological therapeutic value of curcumin in heart failure, we have investigated the translational research of curcumin. This report reviews our basic studies and clinical trials using curcumin therapeutically to prevent heart failure, as well as the possibility of clinical applications of curcumin.

Topics: Animals; Biological Availability; Biological Products; Curcuma; Disease Models, Animal; Heart Failure; Humans; Phytotherapy; Polyphenols; Rats; Translational Research, Biomedical

Heart failure is a major public health concern and one of the most common reasons for a cardiac hospital admission. Heart failure may be classified as having a reduced or preserved ejection fraction and its severity is based on the symptom score. Given the aging population, it is predicted that admissions with heart failure will increase. Whilst pharmacological therapy has improved the associated morbidity and mortality, there is a need for additional therapies to improve the clinical outcome as the death rate remains high. Curcumin is a natural product derived from turmeric that appears to have cardiovascular benefit through a number of mechanisms. In this review, we have assessed the mechanisms by which curcumin may exert its effects in different models of heart failure and show that it has promise as a complementary treatment in heart failure.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biological Products; Cardiotonic Agents; Curcuma; Curcumin; Disease Models, Animal; Heart; Heart Failure; Humans

　Hemodynamic stresses, including hypertension and myocardial infarction, activate neurohumoral factors such as the sympathetic nervous system and the renin-angiotensin system, and can lead to the progression of heart failure. Established pharmacological agents such as angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and β-blockers target extra-cellular molecules and receptors on the cell membrane. These agents have shown some efficacy for the treatment of heart failure, but the long-term survival rate of patients with heart failure remains low. Additional effective pharmacological approaches are urgently required. Our previous studies have demonstrated that curcumin, a natural polyphenol derived from the root of Curcuma longa, prevented the development of heart failure in rat models of myocardial infarction and hypertensive heart disease. However, until recently curcumin's poor water solubility and extremely low bioavailability have presented serious challenges to its clinical applicability. In recent years, highly absorbable curcumin preparations have been developed using methods such as nanoparticle formation and micellization, and there are now high expectations for their wide clinical application. Our group has developed a highly absorbable curcumin formulation called Theracurmin using nanoparticulation and surface processing techniques. Our preliminary data indicated that Theracurmin may improve left ventricular diastolic function. Furthermore, we have already completed and are currently carrying out several clinical trials using Theracurmin against heart failure-related diseases. This paper summarizes and discusses the potential clinical applications of curcumin, focusing on our highly absorbable curcumin formulation, Theracurmin.

Topics: Administration, Oral; Animals; Biological Availability; Curcumin; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Compounding; Heart Failure; Humans; Life Style; Nanoparticles; Nanotechnology; Phytotherapy; Pulmonary Disease, Chronic Obstructive; Rats; Solubility

Heart failure is one of the leading causes of death throughout the world. During the development and deterioration processes of heart failure, cardiomyocytes undergo maladaptive hypertrophy by altering hypertrophy-related gene expression. The zinc finger protein GATA4 is one of the transcription factors involved in the regulation of cardiomyocyte hypertrophy. In response to hypertrophic stimuli such as the synaptic nervous and rennin-angiotensin systems, GATA4 forms a large complex with various functional proteins including an intrinsic histone acetyltransferase, p300, and the disruption of this complex results in the inhibition of hypertrophic responses in cardiomyocytes. While such a transcriptional signal pathway is recognized as a critical event during cardiomyocyte hypertrophy, pharmacological heart failure therapy that targets this pathway has not been established. In order to develop novel heart failure therapy targeting the pathway in cardiomyocytes, we have studied the potential of curcumin, a p300 histone acetyltransferase inhibitor, as an agent for novel heart failure therapy. In this review, we describe a recent study on the cardiac transcriptional signal pathway, especially p300/GATA4 pathway, and a novel heart failure therapy using curcumin.

Topics: Animals; Cardiomegaly; Cardiotonic Agents; Curcumin; Enzyme Inhibitors; Heart Failure; Humans; Myocytes, Cardiac; Transcription, Genetic

Hypertensive heart disease and post-myocardial-infarction heart failure (HF) are leading causes of cardiovascular mortality in industrialized countries. To date, pharmacological agents that block cell surface receptors for neurohormonal factors have been used, but despite such conventional therapy, HF is increasing in incidence worldwide. During the development and deterioration process of HF, cardiomyocytes undergo maladaptive hypertrophy, which markedly influences their gene expression. Regulation of histone acetylation by histone acetyltransferase (eg, p300) and histone deacetylase plays an important role in this process. Increasing evidence suggests that the excessive acetylation of cardiomyocyte nuclei is a hallmark of maladaptive cardiomyocyte hypertrophy. Curcumin inhibits p300-mediated nuclear acetylation, suggesting its usefulness in HF treatment. Clinical application of this natural compound, which is inexpensive and safe, should be established in the near future.

Topics: Acetylation; Cardiomegaly; Curcumin; Gene Expression Regulation; Heart Failure; Humans; Myocytes, Cardiac; p300-CBP Transcription Factors

Topics: Acetylation; Animals; Blood Pressure; Curcumin; Fibrosis; Heart Failure; Hypertension; Hypertrophy, Left Ventricular; Male; Myocytes, Cardiac; Rats; Rats, Inbred Dahl; Sodium Chloride, Dietary; Stroke Volume

Heart failure was subsequently noted in 2-4% of patients on bevacizumab (BEV). Whereas mitochondria play an important role in myocardial tissue homeostasis, deterioration in mitochondrial function will eventually lead to cardiomyocyte cell death and consequently cardiovascular dysfunction. Therefore, the aim of our study is to search the effects of BEV on isolated rat heart mitochondria and cardiomyocytes, and survey the effect of curcumin as a mitochondrial protective and cardioprotective agent. Rat heart mitochondria and cardiomyocytes were isolated from adult rat heart ventricular. By using biochemical and flow cytometry evaluations, the parameters of mitochondrial toxicity including succinate dehydrogenase (SDH) activity, mitochondrial swelling, mitochondrial membrane potential (MMP) collapse, reactive oxygen species (ROS) formation and lipid peroxidation (LP), and cellular assays such as cytotoxicity and MMP collapse were evaluated. Results revealed that BEV (up to 50 μg/ml) induced a concentration- and time-dependent rise in mitochondrial ROS formation, MMP collapse, mitochondrial swelling, LP, and inhibition of SDH in rat heart mitochondria. Our results showed that curcumin (10-100 μM) significantly ameliorated BEV-induced mitochondrial toxicities. Also, our results in cellular assays confirmed amelioration effect of curcumin against BEV toxicity. These results indicate that the cardiotoxic effects of BEV are associated with mitochondrial dysfunction and ROS formation, which finally ends in MMP collapse and mitochondrial swelling as the "point of no return" in the cascade of events leading to apoptosis. Also, results of this study suggest that probably the combination therapy of BEV and curcumin could decrease mitochondrial effects of this drug.

Topics: Angiogenesis Inhibitors; Animals; Antioxidants; Apoptosis; Bevacizumab; Cardiotoxicity; Curcumin; Heart Failure; Lipid Peroxidation; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Swelling; Myocytes, Cardiac; Oxidative Stress; Rats, Wistar; Reactive Oxygen Species

Curcumin is a naturally occurring p300-histone acetyltransferase (p300-HAT) inhibitor that suppresses cardiomyocyte hypertrophy and the development of heart failure in experimental animal models. To enhance the therapeutic potential of curcumin against heart failure, we produced a series of synthetic curcumin analogues and investigated their inhibitory activity against p300-HAT. The compound with the strongest activity was further evaluated to determine its effects on cardiomyocyte hypertrophy and pressure overload-induced heart failure in mice. We synthesised five synthetic curcumin analogues and found that a compound we have named GO-Y030 most strongly inhibited p300-HAT activity. Furthermore, 1 μM GO-Y030, in a manner equivalent to 10 µM curcumin, suppressed phenylephrine-induced hypertrophic responses in cultured cardiomyocytes. In mice undergoing transverse aortic constriction surgery, administration of GO-Y030 at a mere 1% of an equivalently-effective dose of curcumin significantly attenuated cardiac hypertrophy and systolic dysfunction. In addition, this low dose of GO-Y030 almost completely blocked histone H3K9 acetylation and eliminated left ventricular fibrosis. A low dose of the synthetic curcumin analogue GO-Y030 effectively inhibits p300-HAT activity and markedly suppresses the development of heart failure in mice.

Topics: Animals; Cardiomegaly; Curcumin; Heart Failure; Male; Mice; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley

A hallmark of chronic heart failure (HF) with low ejection fraction (HFrEF) is exercise intolerance. We hypothesized that reduced expression of nuclear factor E2-related factor 2 (Nrf2) in skeletal muscle contributes to impaired exercise performance. We further hypothesized that curcumin, a Nrf2 activator, would preserve or increase exercise capacity in HF. Experiments were carried out in mice with coronary artery ligation-induced HFrEF. Curcumin was deliveried by a subcutaneous osmotic minipump at a dose of 50 mg·kg

Topics: Animals; Antioxidants; Coronary Vessels; Curcumin; Disease Models, Animal; Exercise Tolerance; Heart Failure; Heme Oxygenase-1; Ligation; Male; Membrane Proteins; Mice, Inbred C57BL; Muscle Contraction; Muscle Fatigue; Muscle Strength; Muscle, Skeletal; MyoD Protein; Myogenin; NF-E2-Related Factor 2; Signal Transduction; Superoxide Dismutase; Time Factors

Curcumin, isolated from rhizome of turmeric, has been widely studied as a potential therapeutic drug for cancer. However, protective effects of curcumin on chronic heart failure (CHF) have not been fully studied. In the present study, the effects of curcumin on CHF and the underlying mechanisms were investigated. A total of 40 rabbits were randomized into 4 groups: Control rabbits fed with placebo (Con) or curcumin (Con‑cur), CHF rabbits fed with placebo (CHF) or curcumin (CHF‑cur). CHF was induced by volume and pressure overload. The effects of curcumin on cardiac function and left ventricular (LV) structure were assessed by echocardiography and histology. The effects of curcumin on CHF molecular biomarkers were detected by dihydroethidium and immunohistochemical staining. The effects of curcumin on Dickkopf‑related protein 3 (DKK‑3), p38 mitogen‑activated protein kinase (p38), c‑Jun N‑terminal kinase (JNK) and apoptosis signal‑regulating kinase 1 (ASK1) were assessed by immunohistochemical staining and western blot analysis. Cardiac dysfunction and LV remodeling were successfully produced by ten weeks volume overload and eight weeks pressure overload in the CHF group. Compared with the Con group, the CHF group demonstrated higher levels of CHF molecular biomarkers, a lower level of DKK‑3 expression and alterations of p38, JNK and ASK1 protein expression. Curcumin alleviated all those abnormalities markedly in the CHF‑cur group. In summary, curcumin may exert cardioprotective effects by up‑regulating DKK‑3, which in turn may inhibit p38 and JNK signaling pathways in an ASK1‑dependent way. The present study demonstrated that Dickkopf‑3 upregulation mediates the cardioprotective effects of curcumin on chronic heart failure for the first time.

Topics: Animals; Cardiotonic Agents; Chronic Disease; Curcumin; Heart; Heart Failure; Intercellular Signaling Peptides and Proteins; Male; Myocardium; Rabbits; Up-Regulation

The natural compound, curcumin (CUR), possesses several pharmacological properties, including p300-specific histone acetyltransferase (HAT) inhibitory activity. In our previous study, we demonstrated that CUR could prevent the development of cardiac hypertrophy by inhibiting p300-HAT activity. Other major curcuminoids isolated from Curcuma longa including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are structural analogs of CUR. In present study, we first confirmed the effect of these three curcuminoid analogs on p300-HAT activity and cardiomyocyte hypertrophy. Our results showed that DMC and BDMC inhibited p300-HAT activity and cardiomyocyte hypertrophy to almost the same extent as CUR. As the three compounds have structural differences in methoxy groups at the 3-position of their phenol rings, our results suggest that these methoxy groups are not involved in the inhibitory effects on p300-HAT activity and cardiac hypertrophy. These findings provide useful insights into the structure-activity relationship and biological activity of curcuminoids for p300-HAT activity and cardiomyocyte hypertrophy.

Topics: Animals; Cattle; Cells, Cultured; Curcuma; Curcumin; Diarylheptanoids; Heart Failure; Humans; Hypertrophy; Myocytes, Cardiac; p300-CBP Transcription Factors; Phytotherapy; Rabbits; Structure-Activity Relationship

Heart failure (HF) is one of diabetic complications. This work was designed to investigate the possible modulatory effect of curcumin against streptozotocin-induced diabetes and consequently HF in rats. Rats were divided into control, vehicle-treated, curcumin-treated, diabetic-untreated, diabetic curcumin-treated, and diabetic glibenclamide-treated groups. Animal treatment was started 5 days after induction of diabetes and extended for 6 weeks. Diabetic rats showed significant increase in serum glucose, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, nitric oxide, lactate dehydrogenase, cardiac malondialdehyde, plasma levels of interleukin-6, and tumor necrosis factor-alpha, and also showed marked decrease in serum high-density lipoprotein-cholesterol, cardiac reduced glutathione, and cardiac antioxidant enzymes (catalase, superoxide dismutase, and glutathione-S-transferase). However, curcumin or glibenclamide treatment significantly mitigated such changes. In conclusion, curcumin has a beneficial therapeutic effect in diabetes-induced HF, an effect that might be attributable to its antioxidant and suppressive activity on cytokines.

Topics: Animals; Antioxidants; Blood Glucose; Curcumin; Diabetes Mellitus, Experimental; Glutathione; Glyburide; Heart Failure; Inflammation Mediators; Interleukin-6; L-Lactate Dehydrogenase; Male; Myocardium; Nitric Oxide; Organ Size; Oxidative Stress; Rats, Wistar; Streptozocin; Tumor Necrosis Factor-alpha

A natural p300-specific histone acetyltransferase inhibitor, curcumin, may have a therapeutic potential for heart failure. However, a study of curcumin to identify an appropriate dose for heart failure has yet to be performed. Rats were subjected to a left coronary artery ligation. One week later, rats with a moderate severity of myocardial infarction (MI) were randomly assigned to 4 groups receiving the following: a solvent as a control, a low dose of curcumin (0.5 mg∙kg(-1)∙day(-1)), a medium dose of curcumin (5 mg∙kg(-1)∙day(-1)), or a high dose of curcumin (50 mg∙kg(-1)∙day(-1)). Daily oral treatment was continued for 6 weeks. After treatment, left ventricular (LV) fractional shortening was dose-dependently improved in the high-dose (25.2% ± 1.6%, P < 0.001 vs. vehicle) and medium-dose (19.6% ± 2.4%) groups, but not in the low-dose group (15.5% ± 1.4%) compared with the vehicle group (15.1% ± 0.8%). The histological cardiomyocyte diameter and perivascular fibrosis as well as echocardiographic LV posterior wall thickness dose-dependently decreased in the groups receiving high and medium doses. The beneficial effects of oral curcumin on the post-MI LV systolic function are lower at 5 compared to 50 mg∙kg(-1)∙day(-1) and disappear at 0.5 mg∙kg(-1)∙day(-1). To clinically apply curcumin therapy for heart failure patients, a precise, optimal dose-setting study is required.

Topics: Animals; Curcumin; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Heart Failure; Male; Myocardial Infarction; Myocytes, Cardiac; p300-CBP Transcription Factors; Rats, Sprague-Dawley; Severity of Illness Index; Systole; Treatment Outcome; Ventricular Function, Left

Curcumin is an inhibitor of p300 histone acetyltransferase activity, which is associated with the deterioration of heart failure. We reported that native curcumin, at a dosage of 50 mg/kg, prevented deterioration of the systolic function in rat models of heart failure. To achieve more efficient oral pharmacological therapy against heart failure by curcumin, we have developed a novel drug delivery system (DDS) which markedly increases plasma curcumin levels. At the dosage of 0.5 mg/kg, DDS curcumin but not native curcumin restored left ventricular fractional shortening in post-myocardial infarction rats. Thus, our DDS strategy will be applicable to the clinical setting in humans.

Topics: Administration, Oral; Animals; Cardiotonic Agents; Curcumin; Disease Models, Animal; Drug Delivery Systems; Gum Arabic; Heart Failure; Hemodynamics; Intestinal Absorption; Male; Myocardial Infarction; p300-CBP Transcription Factors; Plant Gums; Rats; Rats, Sprague-Dawley

A natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin, may have therapeutic potential for heart failure. However, it is unclear whether curcumin exhibits beneficial additive or synergistic effects on conventional therapy with angiotensin-converting enzyme inhibitors (ACEIs).. Rats were subjected to a sham operation or left coronary artery ligation. One week later, 34 rats with a moderate sized myocardial infarction (MI) were randomly assigned to 4 groups: solvents as control (n = 8), enalapril (an ACEI, 10 mg·kg⁻¹·day⁻¹) alone (n=8), curcumin (50 mg·kg⁻¹·day⁻¹) alone (n = 9) and enalapril plus curcumin (n = 9). Daily oral treatment was repeated and continued for 6 weeks. Echocardiographic data were similar among the 4 groups before treatment. After treatment, left ventricular (LV) fractional shortening (FS) was significantly higher in the enalapril (29.0 ± 1.9%) and curcumin (30.8 ± 1.7%) groups than in the vehicle group (19.7 ± 1.6%). Notably, LVFS further increased in the enalapril/curcumin combination group (34.4 ± 1.8%). Histologically, cardiomyocyte diameter in the non-infarct area was smaller in the enalapril/curcumin combination group than in the enalapril group. Perivascular fibrosis was significantly reduced in the enalapril/curcumin group compared with the curcumin group.. A natural non-toxic dietary compound, curcumin, combined with an ACEI exerts beneficial effects on post-MI LV systolic function in rats.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Curcumin; E1A-Associated p300 Protein; Electrocardiography; Enalapril; Heart Failure; Histone Deacetylase Inhibitors; Male; Myocardial Infarction; Rats; Rats, Sprague-Dawley; Systole; Ventricular Function, Left

To investigate the effects of curcumin on sarcoplasmic reticulum Ca2+-ATPase in heart failure rabbits.. Rabbit heart failure model was made with aortic regurgitation and abdominal aorta constriction and 40 rabbits were randomly divided into 4 groups including: (1) heart failure treated with curcumin; (2) heart failure treated with placebo; (3) healthy control treated with curcumin and (4) healthy control treated with placebo. All rabbits were administrated with curcumin capsules or placebo capsules 100 mg x kg(-1) x d(-1), respectively. All groups were sacrificed after eight weeks. Myocardial ultrastructural organization was detected by transmission electron microscope. RT-PCR and Western blot were used to measure the expression of sarcoplasmic reticulum Ca2+-ATPase in mRNA and protein levels, respectively. Malachite green colorimetric assay was used to evaluate the activity of sarcoplasmic reticulum Ca2+-ATPase.. All detected parameters were similar between control curcumin group and control placebo group. Compared with the control groups (Groups 3 and 4), the heart/body weight ratio was significantly increased in the heart failure-curcumin group (Group 1) and the heart failure-placebo group (Group 2, all P < 0.05), but the ratio was significantly lower in heart failure-curcumin group than in heart failure-placebo group (P < 0.05). The degree of heart failure was decreased by curcumin. Activity and mRNA and protein expression for sarcoplasmic reticulum Ca2+-ATPase were significantly reduced in the heart failure-placebo group and which could be significantly attenuated by curcumin (all P < 0.05).. Curcumin could improve cardiac function via upregulating the expression of sarcoplasmic reticulum Ca2+-ATPase in this model.

Topics: Animals; Calcium; Curcumin; Heart Failure; Rabbits; RNA, Messenger; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases

To investigate the effects of Curcumin on rabbits with chronic heart failure.. Heart failure was induced by combined aortic regurgitation and aortic stenosis in 20 New Zealand rabbits and treated with placebo (HF, n = 10) and Curcumin (Cur, 100 mgxkg(-1)xd(-1), n = 10) for 8 weeks, 10 sham operated rabbits served as controls (Con). Echocardiography was performed in all rabbits at baseline and 8 weeks later. Aortic diameter (AO), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic dimension (LVDs), left ventricular end-diastolic dimension (LVDd), left ventricular posterior wall thickness (LVPW) and interventricular septum thickness (IVS) were measured. Myocardial matrix metalloproteinase (MMP)-2 and MMP-9 expressions and fibrosis were determined by immunohistochemistry and Masson staining respectively.. Compared to baseline, LVEF and LVFS were significantly decreased, AO, LVDs, LVDd, LVPW, and IVS significantly increased at 8 weeks after operation in HF group while these changes could be significantly attenuated in Curcumin treated rabbits. The protein expressions of MMP-2 and MMP-9 were significantly down-regulated in HF group and could be significantly up-regulated by Curcumin treatment. The increased collagen deposition in HF group was also significantly reduced by Curcumin treatment.. Curcumin attenuated left ventricular dysfunction and remodeling by up-regulating MMPs expressions and reducing myocardial fibrosis.

Topics: Animals; Curcumin; Heart Failure; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Rabbits; Ventricular Dysfunction, Left

Curcumin, a commonly available spice and alternative medicine, has been tested in the laboratory and the clinic for activity against a wide range of diseases. It is thought to possess antiinflammatory and antioxidant activities and may also function to inhibit histone acetyl transferases, which activate gene expression via chromatin remodeling. Two reports in this issue of the JCI, by Morimoto et al. and Li et al., suggest that curcumin may inhibit cardiac hypertrophy in rodent models and provide beneficial effects after myocardial infarction or in the setting of hypertension (see the related articles beginning on pages 868 and 879, respectively). These results will spur further mechanistic inquiry into the role of chromatin remodeling in the regulation of cardiac homeostasis.

Topics: Animals; Cardiomegaly; Chromatin Assembly and Disassembly; Curcumin; Enzyme Inhibitors; Heart Failure; Histone Deacetylase Inhibitors; Humans; Mice; p300-CBP Transcription Factors; Rats

Hemodynamic overload in the heart can trigger maladaptive hypertrophy of cardiomyocytes. A key signaling event in this process is nuclear acetylation by histone deacetylases and p300, an intrinsic histone acetyltransferase (HAT). It has been previously shown that curcumin, a polyphenol responsible for the yellow color of the spice turmeric, possesses HAT inhibitory activity with specificity for the p300/CREB-binding protein. We found that curcumin inhibited the hypertrophy-induced acetylation and DNA-binding abilities of GATA4, a hypertrophy-responsive transcription factor, in rat cardiomyocytes. Curcumin also disrupted the p300/GATA4 complex and repressed agonist- and p300-induced hypertrophic responses in these cells. Both the acetylated form of GATA4 and the relative levels of the p300/GATA4 complex markedly increased in rat hypertensive hearts in vivo. The effects of curcumin were examined in vivo in 2 different heart failure models: hypertensive heart disease in salt-sensitive Dahl rats and surgically induced myocardial infarction in rats. In both models, curcumin prevented deterioration of systolic function and heart failure-induced increases in both myocardial wall thickness and diameter. From these results, we conclude that inhibition of p300 HAT activity by the nontoxic dietary compound curcumin may provide a novel therapeutic strategy for heart failure in humans.

Topics: Acetylation; Animals; Cardiomegaly; Curcumin; DNA; Enzyme Inhibitors; GATA4 Transcription Factor; Heart Failure; Hypertension; Male; Myocardial Infarction; Myocytes, Cardiac; p300-CBP Transcription Factors; Rats; Systole; Ventricular Function, Left