SCD4 deficiency decreases cardiac steatosis and prevents cardiac remodeling in mice fed a high-fat diet.

Stearoyl-CoA desaturase (SCD) is a lipogenic enzyme that catalyzes formation of the first double bond in the carbon chain of saturated fatty acids. Four isoforms of SCD have been identified in mice, the most poorly characterized of which is SCD4, which is cardiac-specific. In the present study, we investigated the role of SCD4 in systemic and cardiac metabolism.

Sex- and age-dependent susceptibility to ventricular arrhythmias in the rat heart ex vivo.

The incidence of life-threatening ventricular arrhythmias, the most common cause of sudden cardiac death (SCD), depends largely on the arrhythmic substrate that develops in the myocardium during the aging process. There is a large deficit of comparative studies on the development of this substrate in both sexes, with a particular paucity of studies in females. To identify the substrates of arrhythmia, fibrosis, cardiomyocyte hypertrophy, mitochondrial density, oxidative stress, antioxidant defense and intracellular Ca signaling in isolated cardiomyocytes were measured in the hearts of 3- and 24-month-old female and male rats.

Unconventional myosin VI in the heart: Involvement in cardiac dysfunction progressing with age.

Hypertrophic cardiomyopathy is the most common cardiovascular disease, which is characterized by structural and functional myocardial abnormalities. It is caused predominantly by autosomal dominant mutations, mainly in genes encoding cardiac sarcomeric proteins, resulting in diverse phenotypical patterns and a heterogenic clinical course. Unconventional myosin VI (MVI) is one of the proteins important for heart function, as it was shown that a point mutation within MYO6 is associated with left ventricular hypertrophy.

Alterations of Lipid Metabolism in the Heart in Spontaneously Hypertensive Rats Precedes Left Ventricular Hypertrophy and Cardiac Dysfunction.

Disturbances in cardiac lipid metabolism are associated with the development of cardiac hypertrophy and heart failure. Spontaneously hypertensive rats (SHRs), a genetic model of primary hypertension and pathological left ventricular (LV) hypertrophy, have high levels of diacylglycerols in cardiomyocytes early in development. However, the exact effect of lipids and pathways that are involved in their metabolism on the development of cardiac dysfunction in SHRs is unknown.

Influence of Polyurea Composite Coating on Selected Mechanical Properties of AISI 304 Steel.

This paper contains experimental results of mechanical testing of the AISI 304 steel with composite coatings. The main goal was to investigate the impact of the applied polyurea composite coating on selected mechanical properties: Adhesion, impact resistance, static behavior, and, finally, fatigue lifetime of notched specimens. In the paper the following configurations of coatings were tested: EP (epoxy resin), EP_GF (epoxy resin + glass fabric), EP_GF_HF (epoxy resin + glass fabric hemp fiber), EP_PUA (epoxy resin + polyurea) resin, EP_GF_PUA (epoxy resin + glass fabric + polyurea) resin, and EP_GF_HF_PUA (epoxy resin + glass fabric + hemp fiber + polyurea) resin.

Cardiac and renal upregulation of Nox2 and NF-B and repression of Nox4 and Nrf2 in season- and diabetes-mediated models of vascular oxidative stress in guinea-pig and rat.

The superoxide-forming NADPH oxidase homologues, Nox1, Nox2, and Nox5, seem to mediate the pro-atherosclerotic vascular phenotype. The hydrogen peroxide-forming Nox4 afforded vascular protection, likely via NF-E2-related factor-2 (Nrf2) activation and/or Nox2 downregulation in transgenic mice. We hypothesized that oxidative stress in the intact vasculature involves, aside from the upregulation of the superoxide-forming Noxs, the downregulation of the Nox4/Nrf2 pathway.

Omega-3 Fatty Acids Do Not Protect Against Arrhythmias in Acute Nonreperfused Myocardial Infarction Despite Some Antiarrhythmic Effects.

Ventricular arrhythmias are an important cause of mortality in the acute myocardial infarction (MI). To elucidate the effect of the omega-3 polyunsaturated fatty acids (PUFAs) on ventricular arrhythmias in acute nonreperfused MI, rats were fed with normal or eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA)-enriched diet for 3 weeks. Subsequently the rats were subjected to either MI induction or sham operation.

Ivabradine protects against ventricular arrhythmias in acute myocardial infarction in the rat.

Ventricular arrhythmias are an important cause of mortality in the acute myocardial infarction (MI). To elucidate effect of ivabradine, pure heart rate (HR) reducing drug, on ventricular arrhythmias within 24 h after non-reperfused MI in the rat. ECG was recorded for 24 h after MI in untreated and ivabradine treated rats and episodes of ventricular tachycardia/fibrillation (VT/VF) were identified.

Expression of lipogenic genes is upregulated in the heart with exercise training-induced but not pressure overload-induced left ventricular hypertrophy.

Cardiac hypertrophy is accompanied by molecular remodeling that affects different cellular pathways, including fatty acid (FA) utilization. In the present study, we show that cardiac lipid metabolism is differentially regulated in response to physiological (endurance training) and pathological [abdominal aortic banding (AAB)] hypertrophic stimuli. Physiological hypertrophy was accompanied by an increased expression of lipogenic genes and the activation of sterol regulatory element-binding protein-1c and Akt signaling.

[Polyunsaturated fatty acids omega-3 as modulators of intracellular signaling pathways].

Polyunsaturated fatty acids omega-3 (PUFA omega-3), in particular eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are bioactive lipids that positively impact signaling pathways involved in the development of cardiovascular diseases. PUFA omega-3 affect a myriad of molecular pathways, including alteration physical and chemical properties of membrane microdomains, modulation of membrane receptors and channels, regulation of gene expression via nuclear receptors and transcription factors and changes in eicosanoid clasess' profiles and conversion of EPA and DHA to proresolving mediators. This review summarizes our current knowledge regarding the mechanism of cardioprotective action of PUFA omega-3.

Preserved cardiomyocyte function and altered desmin pattern in transgenic mouse model of dilated cardiomyopathy.

Taking advantage of the unique model of slowly developing dilated cardiomyopathy in mice with cardiomyocyte-specific transgenic overexpression of activated Gαq protein (Tgαq*44 mice) we analyzed the contribution of the cardiomyocyte malfunction, fibrosis and cytoskeleton remodeling to the development of heart failure in this model. Left ventricular (LV) in vivo function, myocardial fibrosis, cytoskeletal proteins expression and distribution, Ca(2+) handling and contractile function of isolated cardiomyocytes were evaluated at the stages of the early, compensated, and late, decompensated heart failure in 4-, 12- and 14-month-old Tgαq*44 mice, respectively, and compared to age-matched wild-type FVB mice. In the 4-month-old Tgαq*44 mice significant myocardial fibrosis, moderate myocyte hypertrophy and increased expression of regularly arranged and homogenously distributed desmin accompanied by increased phosphorylation of desmin chaperone protein, αB-crystallin, were found.

[Overview on omega-3 polyunsaturated fatty acids and heart failure].

Despite aggressive pharmacotherapy, heart failure is still clinical problem. Current therapies improve clinical symptoms and slow progression to heart failure, but overall the prognosis remains poor. Evidence from epidemiological, clinical and experimental studies indicates a beneficial role of the omega-3 polyunsaturated fatty acids (omega-3 PUFA) found in fish oils in the prevention and management of heart failure.

Antioxidative activity of sulodexide, a glycosaminoglycan, in patients with stable coronary artery disease: a pilot study.

Background: Oxidative stress may promote chronic inflammation and contribute to accelerated atherogenesis in patients with coronary artery disease (CAD). Sulodexide, a glycosaminoglycan consisting primarily of heparin, has been shown to affect oxidative stress in experimental settings. The purpose of this pilot study was to determine the effect of sulodexide administration on oxidative stress, inflammation and plasma lipids in patients with proven stable CAD.

The cardioprotective effects of fish oil during pressure overload are blocked by high fat intake: role of cardiac phospholipid remodeling.

Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil may prevent development of heart failure through alterations in cardiac phospholipids that favorably impact inflammation and energy metabolism. A high-fat diet may block these effects in chronically stressed myocardium. Pathological left ventricle (LV) hypertrophy was generated by subjecting rats to pressure overload by constriction of the abdominal aorta.

omega-3 polyunsaturated fatty acid supplementation for the treatment of heart failure: mechanisms and clinical potential.

Heart failure (HF) is a complex clinical syndrome with multiple aetiologies. Current treatment options can slow the progression to HF, but overall the prognosis remains poor. Clinical studies suggest that high dietary intake of the omega-3 polyunsaturated fatty acids (omega-3PUFA) found in fish oils (eicosapentaenoic and docosahexaenoic acids) may lower the incidence of HF, and that supplementation with pharmacological doses prolongs event-free survival in patients with established HF.

Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction.

Aims: Clinical studies suggest that intake of omega-3 polyunsaturated fatty acids (omega-3 PUFA) may lower the incidence of heart failure. Dietary supplementation with omega-3 PUFA exerts metabolic and anti-inflammatory effects that could prevent left ventricle (LV) pathology; however, it is unclear whether these effects occur at clinically relevant doses and whether there are differences between omega-3 PUFA from fish [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and vegetable sources [alpha-linolenic acid (ALA)].

Methods And Results: We assessed the development of LV remodelling and pathology in rats subjected to aortic banding treated with omega-3 PUFA over a dose range that spanned the intake of humans taking omega-3 PUFA supplements.

High-sugar diets increase cardiac dysfunction and mortality in hypertension compared to low-carbohydrate or high-starch diets.

Objective: Sugar consumption affects insulin release and, in hypertension, may stimulate cardiac signaling mechanisms that accelerate left ventricular hypertrophy and the development of heart failure. We investigated the effects of high-fructose or sucrose diets on ventricular function and mortality in hypertensive Dahl salt-sensitive rats.

Methods: Rats were fed chows that were either high starch (70% starch, 10% fat by energy), high fat (20% carbohydrates, 60% fat), high fructose (61% fructose, 9% starch, 10% fat), or high sucrose (61% sucrose, 9% starch, 10% fat).

Low-carbohydrate/high-fat diet attenuates pressure overload-induced ventricular remodeling and dysfunction.

Background: It is not known how carbohydrate and fat intake affect the development of left ventricular (LV) hypertrophy and contractile dysfunction in response to pressure overload. We hypothesized that a low-carbohydrate/high-fat diet prevents LV hypertrophy and dysfunction compared with high-carbohydrate diets.

Methods And Results: Rats were fed high-carbohydrate diets composed of either starch or sucrose, or a low-carbohydrate/high-fat diet, and underwent abdominal aortic banding (AAB) for 2 months.

Dietary supplementation with omega-3 PUFA increases adiponectin and attenuates ventricular remodeling and dysfunction with pressure overload.

Objective: Epidemiological studies suggest that consumption of omega-3 polyunsaturated fatty acids (omega-3 PUFA) decreases the risk of heart failure. We assessed the effects of dietary supplementation with omega-3 PUFA from fish oil on the response of the left ventricle (LV) to arterial pressure overload.

Methods: Male Wistar rats were fed a standard chow or a omega-3 PUFA-supplemented diet.

Low-density lipoprotein reduction by simvastatin is accompanied by angiotensin II type 1 receptor downregulation, reduced oxidative stress, and improved endothelial function in patients with stable coronary artery disease.

Objectives: We tested the hypothesis that low-density lipoprotein-cholesterol induces angiotensin II type 1 receptor upregulation that, in turn, accounts for enhanced oxidative stress, and the subsequent endothelial dysfunction in patients with coronary artery disease.

Methods: Brachial artery flow-mediated vasodilation, serum 8-iso-prostaglandin F2alpha (8-isoprostane), and angiotensin II type 1 receptor density on platelets were measured in 19 patients with coronary artery disease, at entry and after 12 weeks of simvastatin therapy, 40 mg/day.

Results: At entry there was a significant linear correlation between: angiotensin II type 1 receptor density and plasma low-density lipoprotein-cholesterol; plasma 8-isoprostane and angiotensin II type 1 receptor density; and flow-mediated vasodilation and 8-isoprostane.

High fructose diet increases mortality in hypertensive rats compared to a complex carbohydrate or high fat diet.

Background: Chronic hypertension leads to cardiac hypertrophy, heart failure, and premature death. Little is known about the impact of dietary macronutrient composition on hypertension-induced cardiac hypertrophy and mortality. We investigated the effects of consuming either a high complex carbohydrate diet, a high simple sugar diet, or a high fat diet on cardiac hypertrophy and mortality in hypertensive Dahl salt-sensitive (DSS) rats.

Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation in pigs.

Steady state concentrations of ATP and ADP in vivo are similar at low and high cardiac workloads; however, the mechanisms that regulate the activation of substrate metabolism and oxidative phosphorylation that supports this stability are poorly understood. We tested the hypotheses that (1) there is parallel activation of mitochondrial and cytosolic dehydrogenases in the transition from low to high workload, which increases NADH/NAD+ ratio in both compartments, and (2) this response does not require an increase in fatty acid oxidation (FAO). Anaesthetized pigs were subjected to either sham treatment, or an abrupt increase in cardiac workload for 5 min with dobutamine infusion and aortic constriction.

Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy.

Currently, a high carbohydrate/low fat diet is recommended for patients with hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate plays in hypertension and the development of pathological left ventricular hypertrophy (LVH) has not been well characterized. Recent studies demonstrate that LVH can also be triggered by activation of insulin signaling pathways, altered adipokine levels, or the activity of peroxisome proliferator-activated receptors (PPARs), suggesting that metabolic alterations play a role in the pathophysiology of LVH. Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy.

Preconditioning protects endothelium by preventing ET-1-induced activation of NADPH oxidase and xanthine oxidase in post-ischemic heart.

The hypothesis was tested that endothelin-1 (ET-1)-induced superoxide (O(2)(-)) generation mediates post-ischemic coronary endothelial injury, that ischemic preconditioning (IPC) affords endothelial protection by preventing post-ischemic ET-1, and thus O(2)(-), generation, and that opening of the mitochondrial ATP-dependent potassium channel (mK(ATP)) triggers the mechanism of IPC. Furthermore, the study was aimed at identifying the source of O(2)(-) mediating the endothelial injury. Langendorff-perfused guinea-pig hearts were subjected either to 30 min ischemia/35 min reperfusion (IR) or were preconditioned prior to IR with three cycles of either 5 min ischemia/5 min reperfusion or 5 min infusion/5 min washout of mK(ATP) opener diazoxide (0.

[Potential impact of carbohydrate and fat intake on cardiac hypertrophy].

Currently, a high carbohydrate/low fat diet is recommended for patients with heart failure and/or hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate might play in the development of LVH and heart failure has not been well characterized. Recent studies demonstrate that cardiomyocyte hypertrophy can also be triggered by activation of insulin signalling pathways, altered adipokine levels or the activity of peroxisome proliferator-activated receptors (PPARs), suggesting that metabolic alterations play a role in the pathophysiology of LVH and heart failure. Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy.