Deubiquitinases are a group of proteins that identify and digest monoubiquitin chains or polyubiquitin chains attached to substrate proteins, preventing the substrate protein from being degraded by the ubiquitin-proteasome system. Deubiquitinases regulate cellular autophagy, metabolism and oxidative stress by acting on different substrate proteins. Recent studies have revealed that deubiquitinases act as a critical regulator in various cardiac diseases, and control the onset and progression of cardiac disease through a board range of mechanism. This review summarizes the function of different deubiquitinases in cardiac disease, including cardiac hypertrophy, myocardial infarction and diabetes mellitus-related cardiac disease. Besides, this review briefly recapitulates the role of deubiquitinases modulators in cardiac disease, providing the potential therapeutic targets in the future.

A 16-month-old girl was referred for tachycardia and upper respiratory tract infection. Echocardiographic examination revealed pericardial effusion, mild mitral regurgitation, and left ventricle systolic dysfunction. Patient was positive for Parainfluenza type 4 virus. Her laboratory tests revealed increased troponin I level. The patient was treated with intravenous immunoglobulin considering acute viral myopericarditis. Two weeks after treatment, midventricular hypertrophy was detected.

Cardiac hypertrophy is the enlargement of cardiomyocytes in response to persistent release of catecholamine which further leads to cardiac fibrosis. Chrysin, flavonoid from honey, is well known for its multifarious properties like antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic. To investigate the cardioprotective potential of chrysin against isoproterenol (ISO), cardiac hypertrophy and fibrosis are induced in rats. Acclimatised male albino Wistar rats were divided into seven groups (n 6): normal (carboxymethyl cellulose at 0·5 % p.o.; as vehicle), hypertrophy control (ISO 3 mg/kg, s.c.), CHY15 + H, CHY30 + H & CHY60 + H (chrysin; p.o.15, 30 and 60 mg/kg respectively + ISO at 3 mg/kg, s.c.), CHY60 (chrysin 60 mg/kg in per se) and LST + H (losartan 10 mg/kg p.o. + ISO 3 mg/kg, s.c.) were treated for 28 d. After the dosing schedule on day 29, haemodynamic parameters were recorded, after that blood and heart were excised for biochemical, histological, ultra-structural and molecular evaluations. ISO administration significantly increases heart weight:body weight ratio, pro-oxidants, inflammatory and cardiac injury markers. Further, histopathological, ultra-structural and molecular studies confirmed deteriorative changes due to ISO administration. Pre-treatment with chrysin of 60 mg/kg reversed the ISO-induced damage to myocardium and prevent cardiac hypertrophy and fibrosis through various anti-inflammatory, anti-apoptotic, antioxidant and anti-fibrotic pathways. Data demonstrated that chrysin attenuated myocardial hypertrophy and prevented fibrosis via activation of transforming growth factor-beta (TGF-β)/Smad signalling pathway.

Cardiac hypertrophy (CH) is an augmentation of either the right ventricular or the left ventricular mass in order to compensate for the increase of work load on the heart. Metabolic abnormalities lead to histological changes of cardiac myocytes and turn into CH. The molecular mechanisms that lead to initiate CH have been of widespread concern, hence the development of the new field of research, metabolomics: one ‘omics’ approach that can reveal comprehensive information of the paradigm shift of metabolic pathways network in contrast to individual enzymatic reaction-based metabolites, have attempted and until now only 19 studies have been conducted using experimental animal and human specimens. Nuclear magnetic resonance spectroscopy and mass spectrometry-based metabolomics studies have found that CH is a metabolic disease and is mainly linked to the harmonic imbalance of glycolysis, citric acid cycle, amino acids and lipid metabolism. The current review will summarise the main outcomes of the above mentioned 19 studies that have expanded our understanding of the molecular mechanisms that may lead to CH and eventually to heart failure.

Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin–eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

The present study evaluated the antihypertrophic potential of the ethanolic extract of Boerhaavia diffusa (BDE), a well-known edible cardiotonic plant reported in Ayurveda against angiotensin II-induced hypertrophy in H9c2 cardiac myoblast cells. Markers of hypertrophy such as cell size, protein content and the concentrations of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were analysed for the confirmation of hypertrophy induction. Angiotensin II (100 nm) caused an increase in cell volume (69·26 (sd 1·21) %), protein content (48·48 (sd 1·64) %), ANP (81·90 (sd 1·22) %) and BNP (108·57 (sd 1·47) %). BDE treatment significantly reduced cell volume, protein content and the concentrations of ANP and BNP (P≤ 0·05) in H9c2 cells. The activity of various antioxidant enzymes and the concentration of reduced glutathione, which was lowered due to hypertrophy, were increased in BDE-treated cells. The BDE treatment also reduced intracellular reactive oxygen species generation, lipid peroxidation and protein carbonyls in cells. In addition, the expression patterns of NF-κβ and transforming growth factor β1 were found to be increased during hypertrophy, and their expressions were reduced on BDE treatment. In vitro chemical assays showed that BDE inhibits angiotensin-converting enzyme and xanthine oxidase in a dose-dependent manner with an estimated 50 % effective concentration (EC50) value of 166·12 (sd 2·42) and 60·05 (sd 1·54) μg/ml, respectively. The overall results clearly indicate the therapeutic potential of B. diffusa against cardiac hypertrophy, in addition to its nutritional qualities.

Fatty acid transport protein 6 (FATP6) is primarily expressed in the heart and seems to be involved in cardiac fatty acid uptake. Therefore, we investigated whether a variation in the 5′-untranslated region of the FATP6 gene is associated with features of the metabolic syndrome and signs of myocardial alteration or heart failure. A total of 755 male participants from a Metabolic Intervention Cohort Kiel were genotyped for the FATP6–7T>A polymorphism (rs2526246) and phenotyped for features of the metabolic syndrome. Participants underwent a glucose tolerance test and the postprandial assessment of metabolic variables after a standardised mixed meal. Left ventricular heart function was evaluated in fifty-four participants. Fasting (P = 0·01) and postprandial (P = 0·02) TAG concentrations were significantly lower in AA homozygotes when compared with wild-type carriers. Homozygosity of allele A was associated with significantly lower postprandial insulin concentrations after a glucose load and significantly lower systolic (P = 0·01) and diastolic (P = 0·01) blood pressure values compared with wild-type carriers. Accordingly, left ventricular heart mass was significantly lower in twenty-seven AA homozygotes in comparison with twenty-seven TT homozygotes, matched for BMI (P = 0·04). In conclusion, the effects of the FATP6 polymorphism on TAG are mediated by affluent dietary fat. The FATP6–7T>A polymorphism may protect from traits of the metabolic syndrome and CVD.

Gene markers for cardiomyocyte growth, proliferation and remodeling were examined in mouse fetuses and adult male offspring exposed to maternal low-protein (LP) diet during pregnancy. Whole heart volume, measured by magnetic resonance imaging, was smaller in day 15 LP fetuses v. those from chow-fed dams (C), whereas heart volume was greater in adult LP v. C offspring. These LP offspring were hypertensive and had larger cardiomyocytes v. C animals. The mRNA levels of cyclin G1, a marker for cell growth, were lower in LP fetal hearts v. C hearts, but similar in the left ventricle of adult LP and C offspring. Opposite trends were found in brain natriuretic peptide levels (a marker of cardiac hypertrophy). Thus, maternal LP during pregnancy results in smaller fetal hearts and is accompanied by changes in expression of genes involved in cardiomyocyte growth, which are associated with cardiac hypertrophy and hypertension in adulthood.

Introduction: The frequent occurrence of prenatal hypertrophy of the muscular ventricular septum has been widely reported in fetuses of diabetic mothers. Objectives: This experimental study was carried out to test the hypothesis that the weight of the heart, the ratio of the cardiac weight to that of the body, the thickness of the muscular ventricular septum, and the myocytic profile within the ventricular septum are all increased in fetuses of diabetic rats in comparison to fetuses of normal rats. Methods: Diabetes was induced in 5 pregnant Wistar rats, bearing 30 fetuses, on the eighth day after conception, by intraperitoneal injection of 50mg/kg of streptozotocin. Five normal pregnant Wistar rats, bearing 20 fetuses, made up the control group. Morphometric data were obtained by a computer-assisted method applied to the measurements of the thickness of the ventricular septum, and myocytic nuclear area. Statistical analysis utilized Student's t-test and Kruskal-Wallis test. Results: The mean thickness of the septum was 675.56 μm (± 159) in the control fetuses, and 904.39 μm (± 262) in the fetuses carried by diabetic mothers (p < 0.001). The cardiac weight was 0.016 g (± 0.004) in the control group, and 0.023 g (± 0.005) in the group of diabetic fetuses (p < 0.001). The ratio of cardiac to body weight was 0.294% (± 0.079) in the control group, and 0.514% (± 0.073) in the diabetic group (p < 0.001). The myocytic nuclear area was 14.70 μm2 in the control group, and 21.43 μm2 in the diabetic group (p < 0.001). Conclusions: The presence of cellular and morphologic cardiac hypertrophy in fetuses of diabetic rats was demonstrated by the significant difference between the two groups for each analyzed feature.

An adverse environmental experience of the growing fetus may lead to permanent changes in the structure and function of organs that may predispose the individual to chronic diseases in later life; however, nothing is known about the occurrence and mechanisms of heart failure. We employed a rat model in which pregnant dams were fed diets containing either 180 g (normal) or 90 g (low) casein/kg for 2 weeks before mating and throughout pregnancy. The ejection fraction (EF) of the pups exposed to the low-protein (LP) diet was severely depressed in the first 2 weeks of life and was associated with an increase in cardiomyocyte apoptosis. This early depressed cardiac function was followed by progressive recovery and normalization of the EF of the offspring in the LP group. The left ventricular (LV) internal diameters were increased between 24 h and 84 d (12 weeks) of age in the LP-exposed group. Although between 3 d and 2 weeks of age the LV wall of the heart in the LP group was thinner, a progressive increase in LV wall thickness was seen. At 40 weeks of age, although the EF was normal, a two-fold elevation in LV end-diastolic pressure, reduced cardiac output, decreased maximum rates of contraction and relaxation, and reduced mean arterial pressure were observed. Our findings demonstrate that exposure of the developing fetus to a maternal LP diet programs cardiac dysfunction in the offspring in later life.

The cardiovascular actions of a commercial chicken-meat extract known as Brand's Essence of Chicken (Cerebos Pacific Ltd, Singapore; BEC) were investigated in normo- and hypertensive rats. The spontaneously-hypertensive rat (SHR), Wistar Kyoto rat (WKY) and Sprague Dawley rat (SD) were used. The effect of oral feeding of BEC on hypertension, cardiac hypertrophy and arteriosclerosis in these animals was studied. The data showed the following effects of oral feeding of BEC: (1) feeding for 30 d did not affect the blood pressure and heart rate (determined telemetrically) of adult SHR and WKY; (2) feeding for 90 d did not affect the development of hypertension in 1-month-old prehypertensive SHR; (3) feeding for 4 d dose-dependently (0·2–3·2 ml/kg per d) attenuated cardiac hypertrophy in experimentally-induced (coarctation of the abdominal aorta) cardiac hypertrophic SD; (4) feeding to 1-month-old prehypertensive SHR for 11 months did not affect the age-related development of hypertension in this animal; (5) there was significant attenuation of the age-related development of hypertension (determined by tail-cuff plethysmography) in the WKY (P=0·011) when the animals drank an average of 7·5 ml BEC/kg body weight per d, measured during the last 2 months of the 11-month treatment period; (6) there was chronic, as in the previous treatment, attenuation of the age-related development of cardiac hypertrophy and arteriosclerosis (quantified morphometrically) in the SHR when the animals drank an average of 2·4 ml BEC/kg per d, measured during the last 2 months of the 11-month treatment period. A parallel study using laboratory-prepared chicken-meat and pork extracts showed that the former, but not the latter, attenuated cardiac hypertrophy in experimentally-induced cardiac hypertrophic SD. These findings, showing that chicken-meat extract (both BEC and laboratory prepared) could have anti-cardiac hypertrophic, anti-hypertensive and anti-arteriosclerotic actions, were unexpected and provoking, and would challenge nutritional scientists with an interest in meat consumption and cardiovascular diseases.