In this Issue
November 2016; volume 311, issue 5
CALL FOR PAPERS | Cardiovascular Epigenetics: Phenotypes and Mechanisms
- The chromatin-binding protein Smyd1 restricts adult mammalian heart growth
This study is the first to demonstrate that loss of a muscle-specific chromatin-binding protein, Smyd1, is sufficient to induce cardiac hypertrophy and failure. Moreover, the findings demonstrate that augmentation of Smyd1 levels can block hypertrophy in cell models. These studies may support novel strategies for cardiac-targeted epigenetic therapy.
CALL FOR PAPERS | Cardiovascular Mitochondria and Redox Control in Health and Disease
- Reduced mitochondrial respiration in the ischemic as well as in the remote nonischemic region in postmyocardial infarction remodeling
After myocardial infarction, areas of chronic ischemia in the left ventricle (LV) persist. Yet, reduction of mitochondrial respiration, ultrastructural reorganization, and glycogen accumulation occur in all LV regions indicating that, not reduced perfusion, but increased hemodynamic load is the major driver for changes.
- Catalase-dependent H2O2 consumption by cardiac mitochondria and redox-mediated loss in insulin signaling
Catalase contributes to H2O2 consumption in cardiac mitochondria, particularly when mitochondria are compromised. Overexpression of catalase (50-fold) within mitochondria prevents diet-induced loss in insulin-stimulated Akt phosphorylation implicating mitochondrial-derived H2O2. Endogenous increases in mitochondrial catalase (∼50%) do not, however, prevent this loss. Catalase likely limits H2O2 toxicity without perturbing redox-dependent signaling.
CALL FOR PAPERS | Plasma Membrane Integrity in Cardiovascular Physiology and Pathophysiology
- Dopamine induces lipid accumulation, NADPH oxidase-related oxidative stress, and a proinflammatory status of the plasma membrane in H9c2 cells
Stress-induced heart failure is associated with excess catecholamines. Research into the cardiotoxic effects of catecholamines has focused almost exclusively on norepinephrine and epinephrine. Here, we show that dopamine also has cardiotoxic effects because it induces lipid accumulation, oxidative stress, and a proinflammatory status of the plasma membrane in H9c2 cells.
- Mitochondrial tRNA mutation with high-salt stimulation on cardiac damage: underlying mechanism associated with change of Bax and VDAC
We examined the effects of mitochondrial transfer RNA (tRNA) mutation and high-salt stimulation on cardiac damage in spontaneously hypertensive rats. tRNA mutation caused increased levels and coexpression of the voltage-dependent anion channel and the apoptosis regulator Bax, which may promote reactive oxygen species formation and initiate apoptosis.
CALL FOR PAPERS | Quantitative Analyses of Coronary Vascular and Cardiac Mechanics in Health and Disease
- Intraspecific scaling laws are preserved in ventricular hypertrophy but not in heart failure
A scaling law analysis was performed to enhance the understanding of fractal-regulated remodeling of coronary arterial trees in moderate left ventricular hypertrophy, severe right ventricular hypertrophy, and congestive heart failure (CHF) pig hearts. The findings show that the altered scaling exponents reflect the impaired structure-function hierarchy of coronary arterial trees in CHF.
CALL FOR PAPERS | Small Vessels-Big Problems: Novel Insights into Microvascular Mechanisms of Diseases
- Pathways for insulin access to the brain: the role of the microvascular endothelial cell
New understanding of the directional flow of subarachnoid cerebrospinal fluid (CSF) through the Virchow-Robin space (VRS) to brain parenchyma, coupled with the demonstration here of rapid, insulin receptor-dependent trapping of plasma insulin by the brain microvasculature, underscores the direct role of insulin's blood-brain barrier transit to insulin delivery to the brain.
Cardiac Excitation and Contraction
- Changes in cardiac Nav1.5 expression, function, and acetylation by pan-histone deacetylase inhibitors
Therapeutic histone deacetylase inhibition with vorinostat or romidepsin significantly reduces ventricular sodium current density and NaV1.5 protein expression. A slight positive shift in the voltage activation curve, presumably the result of lysine acetylation, decreases the inactivation rate at low activating potentials but does not increase the late sodium current amplitude.
Integrative Cardiovascular Physiology and Pathophysiology
- Cardiac neural crest ablation results in early endocardial cushion and hemodynamic flow abnormalities
This study features quantitative phenotyping of cardiac neural crest ablation-induced great vessel defects and valvular defects at four-chambered stages, as well as structural and functional abnormalities in cardiac cushions and blood flow at cardiac looping stages. The imaging tool used to make these measurements was optical coherence tomography.
- Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction
Cardiac BCAA catabolism is dysregulated after MI, which contributes to post-MI cardiac dysfunction and remodeling through activating mTOR. Importantly, our results show that pharmacological enhancement of BCAA catabolism alleviates post-MI cardiac pathologies. This study illustrates that targeting BCAA catabolism may be a novel therapeutic strategy for post-MI heart failure treatment.
- Arterial baroreflex control of sympathetic nerve activity and heart rate in patients with type 2 diabetes
We show for the first time preserved arterial baroreflex control of sympathetic nerve activity in type 2 diabetes patients with selective impairment in cardiac baroreflex control that appears related to obesity. These findings lend important insight into blood pressure regulation in a patient population prone to developing hypertension.
- Resistance-based interval exercise acutely improves endothelial function in type 2 diabetes
This is the first study to demonstrate improved endothelial function after an acute bout of resistance-based interval exercise. Our data indicate a potential therapeutic effect of resistance interval exercise on endothelial function in older adults with and without type 2 diabetes. The mechanisms underlying these effects warrant further investigation.
- Interaction between the muscle metaboreflex and the arterial baroreflex in control of arterial pressure and skeletal muscle blood flow
We found that carotid baroreceptor unloading during muscle metaboreflex activation results in an additive interaction and causes vasoconstriction of all vascular beds, including ischemic active skeletal muscle. However, there is a larger vasoconstriction in other vascular beds causing redistribution of blood flow toward ischemic active skeletal muscle.
- Vascular function assessed by passive leg movement and flow-mediated dilation: initial evidence of construct validity
This study explores the relationship between a novel assessment of vascular health, passive leg movement (PLM), and an established measure, flow-mediated dilation (FMD), to aid in the interpretation and implementation of the novel technique. Overall, positive relationships between PLM and FMD support PLM as a relevant gauge of vascular health.
- Cardiac-deleterious role of galectin-3 in chronic angiotensin II-induced hypertension
Our study suggests that galectin-3 should be considered not merely a marker for heart failure, but also a direct mediator of cardiac inflammation, fibrosis, and dysfunction. Thus, antagonistic strategies targeting galectin-3 may be a novel therapeutic approach in providing cardiac protection in hypertension and heart failure.
- Exercise intensity modulates the appearance of circulating microvesicles with proangiogenic potential upon endothelial cells
Increases in intravascular platelet microvesicle concentration occur during exercise, but this depends on exercise intensity, and correlates with elevations in vascular shear stress and plasma norepinephrine concentration. Circulating microvesicles isolated from exercising humans display proangiogenic potential on cultured endothelial cells. Thus, it is possible that microvesicles are involved in vascular responses to exercise.
- Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation
Focal and excessive neural inputs to the intrinsic cardiac nervous system increase activity and coherence among intrinsic cardiac neurons in association with an increased potential for atrial fibrillation; preemptive vagus nerve stimulation prevents such neurocardiac effects. The antiarrhythmic effects imparted by vagus nerve stimulation have memory.
- Exposure to cigarette smoke abrogates the beneficial effect of ischemic postconditioning
Smoking and hypertension are two major risk factors in coronary heart disease. Patients who smoke often develop hypertension and left ventricular hypertrophy. The results of the present study suggest that patients with these comorbidities might not be protected by postconditioning application during reperfusion following myocardial infarction.
Muscle Mechanics and Ventricular Function
- Exercise training improves neurovascular control and calcium cycling gene expression in patients with heart failure with cardiac resynchronization therapy
Cardiac resynchronization therapy improves neurovascular control and exercise capacity in patients with heart failure (HF) with intraventricular conduction block. Our study shows that, in patients with HF on guideline-recommended pharmacological therapy in whom a biventricular pacemaker has recently been implanted, exercise training further improves exercise tolerance, neurovascular control, and Ca2+-handling gene expression in skeletal muscle.
Signaling and Stress Response
- TNF receptor signaling inhibits cardiomyogenic differentiation of cardiac stem cells and promotes a neuroadrenergic-like fate
Whether tumor necrosis factor-α (TNF) modulates cardiac stem cell (CSC) function is unknown. We show that TNF, primarily via TNF receptor-1, inhibits cardiomyogenic commitment of CSCs, and channels an alternate neuroadrenergic-like fate via both receptors. This suggests that TNF diminishes the efficacy of cardiac repair and enhances local adrenergic activation.
Vascular Biology and Microcirculation
- Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity
Neonatal epileptic seizures produce cerebrovascular disabilities that may contribute to neonatal encephalopathy. This study in newborn pigs provides evidence that selective head cooling during seizures can be used as an effective intervention that protects the neonatal brain by preventing cerebral vascular dysfunction.
- GLP-1 inhibits VEGFA-mediated signaling in isolated human endothelial cells and VEGFA-induced dilation of rat mesenteric arteries
Human endothelial cells from dermal and retinal origin and rat mesenteric resistance arteries express mRNA for GLP-1R. Upon activation with GLP-1, VEGFA-mediated vasodilation is inhibited because of reduction in PLCγ activity, attenuated Ca2+ signaling, and reduced eNOS activity. These findings reveal new aspects of artery functionality after food intake.