The evolution of nutrition research.

"The doctor of the future will no longer treat the human frame with drugs, but will rather cure and prevent disease with nutrition". Thomas Edison's contemplation may come to fruition if the nutritional revolution continues in its current course. Two realizations have propelled the world into a new age of personalized nutrition: (i) food can provide benefits beyond its intrinsic nutrient content, and (ii) we are not all created equal in our ability to realize to these benefits.

Multifunctional role of astrocytes as gatekeepers of neuronal energy supply.

Dynamic adjustments to neuronal energy supply in response to synaptic activity are critical for neuronal function. Glial cells known as astrocytes have processes that ensheath most central synapses and express G-protein-coupled neurotransmitter receptors and transporters that respond to neuronal activity. Astrocytes also release substrates for neuronal oxidative phosphorylation and have processes that terminate on the surface of brain arterioles and can influence vascular smooth muscle tone and local blood flow.

Differential effects of trans and polyunsaturated fatty acids on ischemia/ reperfusion injury and its associated cardiovascular disease states.

Fatty acids have an important role in providing energy for sustained contractile activity and viability of the heart. However, considerable evidence now supports a role for fatty acids in the modulation of cardiovascular pathology as well. This may be beneficial or detrimental due to the structural differences in the various fatty acids.

Effects of dietary flaxseed on atherosclerotic plaque regression.

Dietary flaxseed can retard the progression of atherosclerotic plaques. However, it remains unclear whether these antiatherogenic effects extend to plaque regression. In the present study, the therapeutic potential of dietary flaxseed on atherosclerotic plaque regression and vascular contractile function was evaluated using a novel rabbit model.

Reversal of cardiac dysfunction and subcellular alterations by metoprolol in heart failure due to myocardial infarction.

In order to examine the reversibility of heart failure due to myocardial infarction (MI) by β-adrenoceptor blockade, 12 weeks infarcted rats were treated with or without metoprolol (50 mg/kg/day) for 8 weeks. The depressed left ventricular (LV) systolic pressure, positive and negative rates of changes in pressure development, ejection fraction, fractional shortening and cardiac output, as well as increased LV end-diastolic pressure in 20 weeks MI animals were partially reversed by metoprolol. MI-induced decreases in septum (systolic) thickness as well as increase in LV posterior wall thickness and LV internal diameter were partially or fully reversible by metoprolol.

Role of microangiopathy in diabetic cardiomyopathy.

Although heart disease due to diabetes is mainly associated with complications of the large vessels, microvascular abnormalities are also considered to be involved in altering cardiac structure and function. Three major defects, such as endothelial dysfunction, alteration in the production/release of hormones, and shift in metabolism of smooth muscle cells, have been suggested to produce damage to the small arteries and capillaries (microangiopathy) due to hyperglycemia, and promote the development of diabetic cardiomyopathy. These factors may either act alone or in combination to produce oxidative stress as well as changes in cellular signaling and gene transcription, which in turn cause vasoconstriction and structural remodeling of the coronary vessels.

Mechanisms of subcellular remodeling in heart failure due to diabetes.

Diabetic cardiomyopathy is not only associated with heart failure but there also occurs a loss of the positive inotropic effect of different agents. It is now becoming clear that cardiac dysfunction in chronic diabetes is intimately involved with Ca(2+)-handling abnormalities, metabolic defects and impaired sensitivity of myofibrils to Ca(2+) in cardiomyocytes. On the other hand, loss of the inotropic effect in diabetic myocardium is elicited by changes in signal transduction mechanisms involving hormone receptors and depressions in phosphorylation of various membrane proteins.

Prevention of diabetes-induced cardiovascular complications upon treatment with antioxidants.

Oxidative stress is considered to play an important role in the pathogenesis of diabetes-induced cardiovascular disease (CVD), which is invariably associated with abnormal blood lipid profile, insulin resistance and metabolic syndrome. Stress, smoking, high saturated fat intake as well as low fruit and vegetable intakes have been shown to increase oxidative stress and hyperlipidemia, which increase the predisposition of diabetic subjects to atherosclerosis, stroke and coronary heart disease. The oxidation of low-density lipoprotein by oxidative stress is essential for the development of atherosclerosis, and the reduction in oxidative stress as well as blood glucose and cholesterol is considered critical for the prevention of diabetes-induced CVD.

Bidirectional regulation of nuclear factor-κB and mammalian target of rapamycin signaling functionally links Bnip3 gene repression and cell survival of ventricular myocytes.

Background: Tumor necrosis factor-α and other proinflammatory cytokines activate the canonical nuclear factor (NF)-κB pathway through the kinase IKKβ. Previously, we established that IKKβ is also critical for Akt-mediated NF-κB activation in ventricular myocytes. Akt activates the kinase mammalian target of rapamycin (mTOR), which mediates important processes such as cardiac hypertrophy.

Modification of Ca(2+)-handling in cardiomyocytes by redox sensitive mechanisms in response to ouabain.

We examined the role of redox-sensitive signal transduction mechanisms in modifying the changes in [Ca(2+)](i) produced by ouabain upon incubating adult rat cardiomyocytes with antioxidants or inhibitors of different protein kinases and monitoring alterations in fura-2 fluorescence. Ouabain increased basal [Ca(2+)](i), augmented the KCl-induced increase in [Ca(2+)](i), and promoted oxyradical production in cardiomyocytes. These actions of ouabain were attenuated by an oxyradical scavenging mixture (superoxide dismutase plus catalase), and the antioxidants (N-acetyl-L-cysteine and N-(2-mercaptoproprionyl)glycine).

Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease.

Although vitamin B6 and its metabolite, pyridoxal 5'-phosphate (PLP), have been shown to exert beneficial effects in ischemic heart disease, the mechanisms of their action are not fully understood. Some studies have shown that ventricular arrhythmias and mortality upon the occlusion of coronary artery were attenuated by pretreatment of animals with PLP. Furthermore, ischemia-reperfusion-induced abnormalities in cardiac performance and defects in sarcoplasmic reticular Ca2+-transport activities were decreased by PLP.

Supported liquid extraction in the quantitation of plasma enterolignans using isotope dilution GC/MS with application to flaxseed consumption in healthy adults.

Dietary interventions involving foods that are enriched in lignans, such as flaxseed, are drawing attention due to their beneficial protective effects in various diseases and human conditions. Accurate quantitation of key lignan metabolites such as enterodiol (END) and enterolactone (ENL) is necessary in order to identify factors that may influence overall bioavailability. Here we describe the validation of a novel supported liquid extraction (SLE) method for isolation of plasma enterolignans, END and ENL, using (2)H(6)-labeled isotopes with gas chromatography-mass spectrometry in micro selected ion storage (GC/MS-μSIS) mode.

Activation of proteases and changes in Na+-K+-ATPase subunits in hearts subjected to ischemia-reperfusion.

Previous studies have shown that ischemia-reperfusion (I/R) injury is associated with cardiac dysfunction and changes in sarcolemmal Na(+)-K(+)-ATPase subunits and activity. This study was undertaken to evaluate the role of proteases in these alterations by subjecting rat hearts to different times of global ischemia, as well as reperfusion after 45 min of ischemia. Decreases in Na(+)-K(+)-ATPase activity at 30-60 min of global ischemia were accompanied by augmented activities of both calpain and matrix metalloproteinases (MMPs) and depressed protein content of β(1)- and β(2)-subunits, without changes in α(1)- and α(2)-subunits of the enzyme.

Oxidized LDL enhances stretch-induced smooth muscle cell proliferation through alterations in nuclear protein import.

Mechanical stress contributes to hypertension and atherosclerosis partly through the stimulation of vascular smooth muscle cell (VSMC) proliferation. Oxidized low density lipoprotein (oxLDL) is another important atherogenic factor that can increase VSMC proliferation. The purpose of this study was to investigate whether oxLDL could further enhance the proliferative action of mechanical stretch on VSMC, and to determine the mechanism responsible for this interaction.

Normalization of NF-κB activity in dorsal root ganglia neurons cultured from diabetic rats reverses neuropathy-linked markers of cellular pathology.

Aims/hypothesis: Dorsal root ganglia (DRG) sensory neurons cultured from 3 to 5 month streptozotocin (STZ)-induced diabetic rats exhibit structural and biochemical changes seen in peripheral nerve fibers in vivo, including axonal swellings, oxidative damage, reduced axonal sprouting, and decreased NF-κB activity. NF-κB is a transcription factor required by DRG neurons for survival and plasticity, and regulates transcription of antioxidant proteins (e.g.

Ciliary neurotrophic factor activates NF-κB to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents.

Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics.

Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction.

This study tested the reversal of subcellular remodelling in heart failure due to myocardial infarction (MI) upon treatment with losartan, an angiotensin II receptor antagonist. Twelve weeks after inducing MI, rats were treated with or without losartan (20 mg/kg; daily) for 8 weeks and assessed for cardiac function, cardiac remodelling, subcellular alterations and plasma catecholamines. Cardiac hypertrophy and lung congestion in 20 weeks MI-induced heart failure were associated with increases in plasma catecholamine levels.

Vascular and cardiac effects of grape powder in the spontaneously hypertensive rat.

Background: We previously reported that resveratrol, a polyphenol found in red grapes, attenuated changes in small artery geometry and stiffness, as well as cardiac hypertrophy and cardiac function in the spontaneously hypertensive rat (SHR). However, in addition to resveratrol, grapes contain a variety of bioactive polyphenols such as catechins, anthocyanins, and flavonoids. Therefore, we investigated the effects of grape consumption in SHR.

Implications of protease activation in cardiac dysfunction and development of genetic cardiomyopathy in hamsters.

It has become evident that protein degradation by proteolytic enzymes, known as proteases, is partly responsible for cardiovascular dysfunction in various types of heart disease. Both extracellular and intracellular alterations in proteolytic activities are invariably seen in heart failure associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, hypertensive cardiomyopathy, diabetic cardiomyopathy, and ischemic cardiomyopathy. Genetic cardiomyopathy displayed in different strains of hamsters provides a useful model for studying heart failure due to either cardiac hypertrophy or cardiac dilation.

Trans fat involvement in cardiovascular disease.

Coronary heart disease is becoming a worldwide epidemic and diet and lifestyle are well known contributing factors. Identifying the kinds of foods that may have a cardioprotective or cardiotoxic effect and understanding their molecular mechanisms of action has become of increasing importance. Through largely epidemiological evidence, trans fatty acid (TFA) intake has been associated with a variety of cardiovascular complications including atherosclerosis.

Impaired adenosine monophosphate-activated protein kinase signalling in dorsal root ganglia neurons is linked to mitochondrial dysfunction and peripheral neuropathy in diabetes.

Mitochondrial dysfunction occurs in sensory neurons and may contribute to distal axonopathy in animal models of diabetic neuropathy. The adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signalling axis senses the metabolic demands of cells and regulates mitochondrial function. Studies in muscle, liver and cardiac tissues have shown that the activity of adenosine monophosphate-activated protein kinase and PGC-1α is decreased under hyperglycaemia.

NF-κB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus.

Background: Nuclear factor kappa B (NF-κB) is a transcription factor typically expressed with two specific subunits (p50, p65). Investigators have reported that NF-κB is activated during the induction of in vitro long term potentiation (LTP), a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-κB may be necessary for some aspects of memory encoding. Furthermore, NF-κB has been implicated as a potential requirement in behavioral tests of memory.

The role of aberrant mitochondrial bioenergetics in diabetic neuropathy.

Diabetic neuropathy is a neurological complication of diabetes that causes significant morbidity and, because of the obesity-driven rise in incidence of type 2 diabetes, is becoming a major international health problem. Mitochondrial phenotype is abnormal in sensory neurons in diabetes and may contribute to the etiology of diabetic neuropathy where a distal dying-back neurodegenerative process is a key component contributing to fiber loss. This review summarizes the major features of mitochondrial dysfunction in neurons and Schwann cells in human diabetic patients and in experimental animal models (primarily exhibiting type 1 diabetes).

Intracortical injection of endothelin-1 induces cortical infarcts in mice: effect of neuronal expression of an adenosine transporter.

Background: Activation of adenosine A1 receptors has neuroprotective effects in animal stroke models. Adenosine levels are regulated by nucleoside transporters. In vitro studies showed that neuron-specific expression of human equilibrative nucleoside transporter 1 (hENT1) decreases extracellular adenosine levels and adenosine A1 receptor activity.

Extracellular and intracellular proteases in cardiac dysfunction due to ischemia-reperfusion injury.

Various procedures such as angioplasty, thrombolytic therapy, coronary bypass surgery, and cardiac transplantation are invariably associated with ischemia-reperfusion (I/R) injury. Impaired recovery of cardiac function due to I/R injury is considered to be a consequence of the occurrence of both oxidative stress and intracellular Ca(2+)-overload in the myocardium. These changes in the ischemic myocardium appear to activate both extracellular and intracellular proteases which are responsible for the cleavage of extracellular matrix and subcellular structures involved in the maintenance of cardiac function.