ascorbic-acid and Cardiomegaly

Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.

Topics: Acetylcysteine; Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Ascorbic Acid; Biomarkers; Blood Glucose; Body Weight; Calcium; Cardiomegaly; Cardiotonic Agents; Cytochromes c; Diabetic Cardiomyopathies; Disease Models, Animal; Down-Regulation; GATA4 Transcription Factor; Lipid Peroxidation; Lipids; Mitochondria, Heart; Myocardium; Oxidation-Reduction; Oxidative Stress; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PPAR alpha; Rats, Sprague-Dawley; Reactive Oxygen Species; RNA, Messenger; Selenium

Ageing is an important risk factor of cardiovascular diseases including heart failure. Senescence marker protein 30 (SMP30), which was originally identified as an important ageing marker protein, is assumed to act as a novel anti-ageing factor in various organs. However, the role of SMP30 in the heart has not been previously explored. In this study, our aim was to elucidate the functional role of SMP30 on cardiac remodelling.. SMP30 knockout (KO) mice and wild-type (WT) mice were subjected to continuous angiotensin II (Ang II) infusion. After 14 days, the extent of cardiac hypertrophy and myocardial fibrosis was significantly higher in SMP30-KO mice than in WT mice. Echocardiography revealed that SMP30-KO mice had more severely depressed systolic and diastolic function with left ventricular dilatation compared with WT mice. Generation of reactive oxygen species related with activation of nicotinamide adenine dinucleotide phosphate-oxidase was greater in SMP30-KO mice than in WT mice. The number of deoxynucleotidyl transferase-mediated dUTP nick end-labelling positive nuclei was markedly increased in SMP30-KO mice with activation of caspase-3, increases in the Bax to Bcl-2 ratio and phosphorylation of c-Jun N-terminal kinase compared with WT mice. Furthermore, the number of senescence-associated β-galactosidase-positive cells was significantly increased via up-regulation of p21 gene expression in SMP30-KO mice compared with WT mice.. This study demonstrated the first evidence that deficiency of SMP30 exacerbates Ang II-induced cardiac hypertrophy, dysfunction, and remodelling, suggesting that SMP30 has a cardio-protective role in cardiac remodelling with anti-oxidative and anti-apoptotic effects in response to Ang II.

Topics: Aging; Angiotensin II; Animals; Apoptosis; Ascorbic Acid; bcl-2-Associated X Protein; Biomarkers; Calcium-Binding Proteins; Cardiomegaly; Caspase 3; Disease Models, Animal; Fibrosis; Heart Failure; Intracellular Signaling Peptides and Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Ventricular Remodeling

Senescence marker protein 30 (SMP30) is assumed to behave as an anti-aging factor. Recently, we have demonstrated that deficiency of SMP30 exacerbates angiotensin II-induced cardiac hypertrophy, dysfunction and remodeling, suggesting that SMP30 may have a protective role in the heart. Thus, this study aimed to test the hypothesis that up-regulation of SMP30 inhibits cardiac adverse remodeling in response to angiotensin II.. We generated transgenic mice with cardiac-specific overexpression of SMP30 gene using α-myosin heavy chain promoter. Transgenic mice and wild-type littermate mice were subjected to continuous angiotensin II infusion (800 ng/kg/min).. After 14 days, heart weight and left ventricular weight were lower in transgenic mice than in wild-type mice, although blood pressure was similarly elevated during angiotensin II infusion. Cardiac hypertrophy and diastolic dysfunction in response to angiotensin II were prevented in transgenic mice compared with wild-type mice. The degree of cardiac fibrosis by angiotensin II was lower in transgenic mice than in wild-type mice. Angiotensin II-induced generation of superoxide and subsequent cellular senescence were attenuated in transgenic mouse hearts compared with wild-type mice.. Cardiac-specific overexpression of SMP30 inhibited angiotensin II-induced cardiac adverse remodeling. SMP30 has a cardio-protective role with anti-oxidative and anti-aging effects and could be a novel therapeutic target to prevent cardiac hypertrophy and remodeling due to hypertension.

Topics: Angiotensin II; Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Calcium-Binding Proteins; Cardiomegaly; Cellular Senescence; Diastole; Echocardiography; Fibrosis; Hypertension; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Transgenic; Oxidative Stress; Promoter Regions, Genetic; Superoxides

1. This study investigates the time course of pulmonary arterial hypertension (PAH) due to monocrotaline (MCT) and its association with cardiac function and oxidative stress markers in the left ventricle (LV). 2. Male Wistar rats were divided into six groups: 7 days, 21 days, and 31 days for both control and MCT groups. Following echocardiographic analysis, the heart was removed. The LV was separated and homogenized to analyze oxidized-to-total glutathione ratio and thioredoxin reductase (TrxR) activity as well as hydrogen peroxide (H(2) O(2) ) and ascorbic acid levels. 3. There was significant (P < 0.01) cardiac and right ventricle (RV) hypertrophy and pulmonary congestion in the MCT 21 day and 31 day groups. Echocardiography showed a change in the flow wave of the pulmonary artery at 21 days after MCT treatment. There was an increase in the LV ejection time (P < 0.05) at 31 days after MCT. The LV H(2)O(2) concentration was increased (P < 0.05) in the MCT 21 day and MCT 31 day groups compared with controls. There was a reduction (P < 0.05) in the LV ascorbic acid concentration and an increase (P < 0.05) in TrxR activity in the MCT 31 day rats. 4. Our findings showed RV changes due to pulmonary hypertension at 21 days after MCT injection. There was a correlation between the degree of dysfunction and the morphometry of the heart chambers, along with impairment of the antioxidant/pro-oxidant balance in the LV 31 days after the beginning of the protocol. This study suggests that LV changes follow RV dysfunction subsequent to pulmonary hypertension.

Topics: Animals; Ascorbic Acid; Cardiomegaly; Familial Primary Pulmonary Hypertension; Glutathione; Heart Ventricles; Hydrogen Peroxide; Hypertension, Pulmonary; Male; Monocrotaline; Oxidative Stress; Rats; Rats, Wistar; Thioredoxin-Disulfide Reductase; Ultrasonography

This study was conducted to test whether oxidative stress activates the intracellular protein kinase B (AKT1) signaling pathway, which culminates with cardiac hypertrophy in experimental hyperthyroidism. Male Wistar rats were divided into four groups: control, vitamin E, thyroxine (T(4)), and T(4)+vitamin E. Hyperthyroidism was induced by T(4) administration (12 mg/l in drinking water for 28 days). Vitamin E treatment was given during the same period via s.c. injections (20 mg/kg per day). Morphometric and hemodynamic parameters were evaluated at the end of the 4-week treatment period. Protein oxidation, redox state (reduced glutathione, GSH/glutathione dissulfide, GSSG), vitamin C, total radical-trapping antioxidant potential (TRAP), hydrogen peroxide (H2O2), and nitric oxide metabolites (NO(X)) were measured in heart homogenates. The p-AKT1/AKT1 ratio, p-glycogen-synthase kinase (GSK)3B/GSK3B ratio, FOS, and JUN myocardial protein expression were also quantified by western blot after 4 weeks. Increases in biochemical parameters, such as protein oxidation (41%), H2O2 (62%), and NO(X) (218%), and increase in the left ventricular end-diastolic pressure were observed in the T(4) group. T(4) treatment also caused a decrease in GSH/GSSG ratio (83%), vitamin C (34%), and TRAP (55%). These alterations were attenuated by vitamin E administration to the hyperthyroid rats. Expression of p-AKT1/AKT1, p-GSK3B/GSK3B, FOS, and JUN were elevated in the T(4) group (by 69, 37, 130, and 33% respectively), whereas vitamin E administration promoted a significant reduction in their expression. These results indicate that oxidative stress plays an important role in cardiac hypertrophy, and suggest redox activation of AKT1 and JUN/FOS signaling pathways with H2O2 acting as a possible intracellular mediator in this adaptive response to experimental hyperthyroidism.

Topics: Animals; Ascorbic Acid; Blotting, Western; Cardiomegaly; Disease Models, Animal; Glutathione; Hydrogen Peroxide; Hyperthyroidism; Male; Oxidation-Reduction; Rats; Rats, Wistar; Signal Transduction; Thyroxine

Amyloidosis results from protein infiltration of the extracellular space of organs and tissues. Several amyloidosis proteins have been identified. Protein AL, (deriving from immunoglobulin light chain), protein AA and prealbumin are the most involved in this disease. When AL amyloidosis involves the heart, the illness is often terminal. Most clinical symptoms are heart failure and arrhythmia or block conduction. This case was characterised by the unusual combination of hypertension and amyloidosis. The diagnosis suggested by the echocardiographic but was confirmed by the damaged organ's biopsy. The present case concerns a young woman, who has hypertension and a pulmonary oedema. The echocardiographic scan showed a septal hypertrophy with a shining and granite-like aspect which is compatible with heart amyloidosis. Systolic and diastolic disorder with mitral and aortic regurgitation were also revealed. The kidney and rectum biopsies confirmed amyloidosis AL of the Kappa dysglobulinemia type, without extraosseous plasmocytoma. The heart and kidney failure symptoms disappeared after treatment with diuretics and ACE inhibitors.

Topics: Adult; Amyloidosis; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; Biopsy; Cardiomegaly; Colchicine; Diuretics; Echocardiography; Female; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Immunoglobulin kappa-Chains; Nephritis; Paraproteinemias; Pulmonary Edema; Radiography; Rectum

To clarify the mechanical adaptation and interference of coronary vessels, we studied hemodynamics of coronary circulation in control and 4 different pacing rates (80, 100, 120, 150/min) in 5 patients with angina pectoris (AP) and in 5 patients with hypertrophic cardiomyopathy (HCM). Coronary sinus flow (CSF) was measured by a Webster's thermodilution catheter, and we applied ascorbic acid-platinum reaction for the mean transit time measurement in left coronary flow (t0-t2). Coronary vascular bed (CVB) was obtained by multiplying CSF and t0-t2. CSF in AP gradually increased from 104 +/- 21 ml/min at 72/min to 148 +/- 42 ml/min at 120/min, while CSF in HCM changed slightly from 91 +/- 25 ml/min at 64/min to 94 ml/min at 120/min. Average t0-t2 in HCM was 6.0 +/- 1.6 sec in control which was significantly lower than that in AP (7.8 +/- 0.7 sec). Calculated CVB in AP increased at any given heart rate up to 120/min (13.5 +/- 2.4, 15.8 +/- 1.7, 15.0 +/- 4.7, 15.1 +/- 4.3 ml), but CVB in HCM decreased from 9.1 +/- 2.3 ml at 64/min to 8.1 +/- 1.7 ml at 120/min. These data suggest that myocardial compression and suction at different heart rates and with different cardiac muscle structures play an important role for beat to beat adjustment of coronary circulation in cardiac cycle.

Topics: Adaptation, Physiological; Adult; Aged; Angina Pectoris; Ascorbic Acid; Biomechanical Phenomena; Blood Flow Velocity; Cardiac Pacing, Artificial; Cardiomegaly; Cardiomyopathy, Hypertrophic; Coronary Circulation; Coronary Vessels; Heart; Heart Rate; Hemodynamics; Humans; Middle Aged; Platinum

Catecholamines may be one of the molecular signals linking increased circulatory demand to myocardial hypertrophy, and I have found previously that norepinephrine stimulates hypertrophy of cultured neonatal rat heart muscle cells through an alpha 1-adrenergic receptor. Since catecholamine stimulation of contractility is believed to be under beta-adrenergic control, I asked whether these cultured heart cells had dual pathways regulating growth and contractility through alpha- and beta-adrenergic receptors, respectively. I examined the effect of adrenergic agents on hypertrophy and beating of myocytes in serum-free cultures. Hypertrophy was defined as an increase in myocyte surface area and in cell protein content, measured by a radioisotopic method, and chronotropic activity was examined visually. Norepinephrine and epinephrine were equipotent stimulants of hypertrophy and beating, increasing cell protein and area 1.5- to 2-fold, and the proportion of beating cells from 5% or less to 95%. Response maxima occurred 24-48 hours after exposure, and EC50 were 20-200 nM. Studies with other agonists (phenylephrine, methoxamine, clonidine, isoproterenol, dopamine) and antagonists (prazosin, terazosin, yohimbine, propranolol, betaxolol, ICI 118,551) indicated that hypertrophy was mediated through an alpha 1-adrenergic receptor, whereas the induction of beating required both alpha 1- and beta 1-receptor activation. Hypertrophied cells with minimal beating were produced by alpha-stimulation, alone. In contrast, alpha-plus beta-stimulation in the presence of cycloheximide to inhibit protein synthesis resulted in maximum beating but no hypertrophy. These findings imply that growth and beating can be regulated independently through separate cellular pathways.

Topics: Animals; Ascorbic Acid; Cardiomegaly; Cell Division; Cells, Cultured; Cycloheximide; Dopamine; Heart; Muscle Proteins; Myocardial Contraction; Myocardium; Piperazines; Prazosin; Propranolol; Rats; Receptors, Adrenergic, alpha; Receptors, Adrenergic, beta; Sympathomimetics

Topics: Adult; Ascites; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiomegaly; Edema; Female; Humans; Leg; Scurvy

Topics: Acetylcholine; Adrenal Glands; Adrenal Medulla; Animals; Aortic Valve Insufficiency; Ascorbic Acid; Cardiomegaly; Catecholamines; Corticosterone; Heart; Heart Failure; Hypertension; Myocardium; Norepinephrine; Organ Size; Rabbits