In this Issue
December 2016; volume 311, issue 6
CALL FOR PAPERS | Cardiovascular Actions of Hydrogen Sulfide and Other Gasotransmitters
- Hydrogen sulfide-induced vasodilation mediated by endothelial TRPV4 channels
This is the first study to demonstrate that H2S-induced vasodilation involves TRPV4 channels and strengthens our previous observation that endothelial large-conductance Ca2+-activated K+ channels (BK) participate in vasodilation in small mesenteric arteries.
- H2S concentrations in the heart after acute H2S administration: methodological and physiological considerations
Administration of exogenous H2S was unable to increase the pools of combined H2S in the heart of rats, even after H2S intoxication. Any long-lasting effects of H2S on the heart, previously reported in the literature, do not require a measurable accumulation of H2S in cardiac tissue.
CALL FOR PAPERS | Cardiovascular Epigenetics: Phenotypes and Mechanisms
- Parental vitamin D deficiency during pregnancy is associated with increased blood pressure in offspring via Panx1 hypermethylation
Parental vitamin D deficiency is associated with increased blood pressure in the offspring and with epigenetic changes of Panx1, a gene encoding for a hemichannel involved in endothelial-dependent relaxation. Offspring from vitamin D-depleted parents have impaired endothelial relaxation of the large vessels, suggesting an underlying biological mechanism.
CALL FOR PAPERS | Small Vessels-Big Problems: Novel Insights into Microvascular Mechanisms of Diseases
- Coronary microvascular dysfunction after long-term diabetes and hypercholesterolemia
Coronary microvascular dysfunction (CMD) is an increasingly recognized feature of coronary artery disease. We found that progression of CMD in diabetic + hypercholesterolemic swine from 2.5 to 15 mo of follow-up involved a shift from impaired endothelium-dependent vasodilation to bradykinin to exaggerated vasoconstriction to endothelin, highlighting the time dependence of the phenotype of CMD.
Cardiac Excitation and Contraction
- Dyssynchronous calcium removal in heart failure-induced atrial remodeling
In atrial cells from failing hearts excitation-contraction coupling undergoes profound remodeling. Ca transients are larger in amplitude, the decline of intracellular Ca concentration ([Ca]i) is accelerated, and diastolic Ca removal shows profound spatial inhomogeneity and dyssynchrony that, together with an upregulation of Na/Ca exchange, generate a substrate for proarrhythmic Ca release.
- Spontaneous initiation of premature ventricular complexes and arrhythmias in type 2 long QT syndrome
Under type 2 long QT conditions, cellular phase 2 early afterdepolarizations are suppressed by repolarization gradient, but tissue-scale phase 3 early afterdepolarizations occur spontaneously via dynamical instabilities caused by repolarization gradient and enhanced L-type calcium current, resulting in both the trigger and the vulnerable substrate simultaneously for spontaneous initiation of arrhythmias.
Cardiovascular Neurohormonal Regulation
- Effects of various types of anesthesia on hemodynamics, cardiac function, and glucose and lipid metabolism in rats
This study is the first to comprehensively compare the effects of different types of anesthesia commonly used for small animals on hemodynamic, cardiac, hormonal, and metabolic factors. We should select the most appropriate type of anesthesia for studies, considering the possible effects of anesthesia on the parameters to be measured.
Integrative Cardiovascular Physiology and Pathophysiology
- Heart-lung interaction in a model of COPD: importance of lung volume and direct ventricular interaction
Mechanisms of adverse cardiopulmonary interaction in chronic obstructive pulmonary disease (COPD) remain unclear. Using a novel healthy human model of COPD, we demonstrate that lung hyperinflation impairs left ventricular (LV) function to a greater extent than increased negative intrathoracic pressure and provide quantitative evidence for the role of direct ventricular interaction in reducing LV stroke volume.
- Exercise-induced brachial artery blood flow and vascular function is impaired in systemic sclerosis
Systemic sclerosis is characterized by debilitating fibrosis and vascular dysfunction; however, little is known about the circulatory response to exercise in this population. This study reveals attenuated brachial artery blood flow and arterial vasodilatory dysfunction during handgrip exercise in SSc and suggests elevated oxidative stress may play a role.
- Influence of menopause status and age on integrated central and peripheral hemodynamic responses to subsystolic cuffing during submaximal exercise
These data suggest locomotor muscle subsystolic cuffing during submaximal exercise provokes an increased pressor reflex in adult women. However, in demonstrating increased arterial pressure despite maintained cardiac output, postmenopausal women may rely to a greater extent on influences that musculoskeletal afferent fibers have on sympathetically mediated vasoconstriction to generate blood pressure.
- Toll-like receptor 9 prevents cardiac rupture after myocardial infarction in mice independently of inflammation
In the present study, we demonstrate that ablation of Toll-like receptor 9 (TLR9) causes cardiac rupture after myocardial infarction. Although the TLR9 signaling pathway is not involved in the acute inflammatory response in infarct hearts, it promotes proliferation and differentiation of cardiac fibroblasts during postinfarct repair.
- Fluid mechanics of human fetal right ventricles from image-based computational fluid dynamics using 4D clinical ultrasound scans
Based on clinical ultrasound scans of three 20-wk-old normal human fetuses, we performed computational fluid dynamics simulations of the right ventricles to characterize flow and energy dynamics. Results showed interesting and complex flow patterns and energy dynamics and serve as a baseline for future comparison with diseased hearts.
- Physiological and hypoxic oxygen concentration differentially regulates human c-Kit+ cardiac stem cell proliferation and migration
Physiological (5%) oxygen is optimal for proliferation and migration of c-kit+ cardiac stem cells (CSCs) compared with room air (21%) and hypoxia (0.5%). A novel regulatory role of oxygen concentration on proliferation, senescence, and migration of CSCs is demonstrated that has implications for the production and development of CSC therapies.
- Dietary nitrate supplementation attenuates the reduction in exercise tolerance following blood donation
Dietary nitrate supplementation with beetroot juice lowered the O2 cost of moderate-intensity exercise, better preserved muscle oxygenation, and attenuated the decline in incremental exercise test performance following donation of 450 ml of whole blood. These results have implications for improving functional capacity following blood loss.
- Limitations of skeletal muscle oxygen delivery and utilization during moderate-intensity exercise in moderately impaired patients with chronic heart failure
This study provides novel evidence for heterogeneity regarding O2 delivery or utilization impairments to moderate-intensity exercise in patients with chronic heart failure by near-infrared spectroscopy measurements of skeletal muscle oxygenation. Slowed deoxygenation during onset was related to an O2 utilization impairment, whereas a deoxygenation overshoot indicated an O2 delivery to utilization mismatch.
Signaling and Stress Response
- Carboxy-terminal deletion of the HDL receptor reduces receptor levels in liver and steroidogenic tissues, induces hypercholesterolemia, and causes fatal heart disease
Deletion of the mouse HDL receptor SR-BI's three carboxy-terminal residues induces hypercholesterolemia and decreased receptor expression in liver and steroidogenic tissues, suggesting previously unrecognized carboxy terminus-binding adaptor protein in steroidogenic cells. SR-BIΔCT/apoE knockout mice fed a regular chow diet show severe coronary heart disease and premature death secondary to myocardial infarction.
- FOXO3a regulates BNIP3 and modulates mitochondrial calcium, dynamics, and function in cardiac stress
This is the first study to investigate the role of FOXO3a in cardiac stress, with focus on its role in modulating mitochondrial function and cardiac energetics and function. The gene delivery of dominant-negative FOXO3a in heart failure with preserved ejection fraction improved mitochondrial ultrastructure and function as well as myocardial and, particularly, diastolic function.
Vascular Biology and Microcirculation
- Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina
We examined the impact of CYP2C19 genotypes and epoxyeicosatrienoic acid (EET) on patients with microvascular angina (MVA). In results, the CYP2C19 poor metabolizer genotype may be a new candidate risk factor for MVA via EET.
- Ion channel mechanisms of rat tail artery contraction-relaxation by menthol involving, respectively, TRPM8 activation and L-type Ca2+ channel inhibition
Although the cold and menthol receptor, calcium-permeable transient receptor potential melastatin 8 (TRPM8), channel is expressed in vascular smooth muscles, surprisingly menthol causes vasorelaxation. Here we dissect the true contractile response of rat tail artery myocytes to TRPM8 activation, which is normally “masked” by the nonspecific inhibition of voltage-activated L-type calcium channels, resulting in vasorelaxation.
- Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial
This study tested the glutathione peroxidase mimetic ebselen in clinically relevant doses and found no significant impact on either oxidative stress or conduit artery vascular function in subjects with diabetes.
- Microstructure and mechanics of human resistance arteries
This is the first study to elucidate and quantify the microstructural bases of the mechanical properties of human resistance arteries. The geometrically accurate mechanical analysis provides new insights into strain fields existing in the walls of small arteries, and raises questions about the mechanobiology of vascular remodeling.