In this Issue
April 2017; volume 312, issue 4
- The history of the microsphere method for measuring blood flows with special reference to myocardial blood flow: a personal memoir
The contributions of the various individuals who developed the microsphere method of measuring regional blood flows and how these advances took place are brought to light in this paper.
RESEARCH ARTICLES | Cardiac Excitation and Contraction
- Silica nanoparticles induce cardiotoxicity interfering with energetic status and Ca2+ handling in adult rat cardiomyocytes
Silica particles are used as novel nanotechnology-based vehicles for diagnostics and therapeutics for the heart. However, their potential hazardous effects remain unknown. Here, the cardiotoxicity of silica nanoparticles in rat myocytes has been described for the first time, showing an impairment of mitochondrial function that interfered directly with Ca2+ handling.
- Development of dilated cardiomyopathy and impaired calcium homeostasis with cardiac-specific deletion of ESRRβ
Estrogen-related receptor-β (ESRRβ) is highly expressed in the heart and cardiac-specific deletion results in the development of a dilated cardiomyopathy (DCM). ESRRβ is mislocalized in human myocardium samples with DCM, suggesting a possible role for ESRRβ in the pathogenesis of DCM in humans.
RESEARCH ARTICLE | Cardiovascular Actions of Hydrogen Sulfide and Other Gasotransmitters
- Cystathionine γ-lyase protects vascular endothelium: a role for inhibition of histone deacetylase 6
Oxidative injury to endothelial cells by oxidized LDL reduced cystathionine γ-lyase (CSEγ) expression and H2S production, leading to endothelial dysfunction, which was prevented by histone deacetylase 6 (HDAC6) inhibition. Our data suggest HDAC6 as a novel therapeutic target to prevent the development of atherosclerosis.
RESEARCH ARTICLE | Cardiovascular Neurohormonal Regulation
- Optogenetic identification of hypothalamic orexin neuron projections to paraventricular spinally projecting neurons
This is the first study to establish, using innovative optogenetic approaches in a transgenic rat model, that there are robust heterogeneous projections from orexin neurons to paraventricular spinally projecting neurons, including excitatory glutamatergic and inhibitory GABAergic neurotransmission. Endogenous orexin release modulates glutamatergic, but not GABAergic, neurotransmission in these pathways.
RESEARCH ARTICLE | Heart Failure: Novel Therapeutic Pathways Emerging from Basic Science
- Exosomes from pediatric dilated cardiomyopathy patients modulate a pathological response in cardiomyocytes
The results of this work could alter the present paradigm of basing clinical pediatric heart failure (HF) treatment on outcomes of adult HF clinical trials. The use of serum-treated primary cardiomyocytes may define age-specific mechanisms in pediatric HF with the potential to identify unique age-appropriate and disease-specific therapy.
RESEARCH ARTICLES | Integrative Cardiovascular Physiology and Pathophysiology
- Oscillatory lower body negative pressure impairs working memory task-related functional hyperemia in healthy volunteers
We show that induced cerebral blood flow oscillations suppress functional hyperemia produced by a working memory task as well as memory task performance. We conclude that oscillatory cerebral blood flow produces causal reductions of memory task neurovascular coupling and memory task performance. Reductions of functional hyperemia are constrained by autoregulation.
- A systems genetics approach identifies Trp53inp2 as a link between cardiomyocyte glucose utilization and hypertrophic response
Here, we apply a novel method for screening transcripts based on a substrate-specific expression pattern to identify Trp53inp2 as an induced cardiomyocyte glucose utilization factor. We further show that reducing expression of the gene could effectively blunt hypertrophic response in the context of elevated glucose content.
- Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet
Western diet abolished protective effect of sex against cardiovascular disease (CVD) development in premenopausal animals with metabolic syndrome. Western diet accelerates progression of CVD in male and female animals with preexisting metabolic syndrome but not normal animals. Exacerbation of baseline oxidative stress correlates with accelerated progression of CVD in metabolic syndrome animals on Western diet.
- Blockade of CaMKII depresses conduction preferentially in the right ventricular outflow tract and promotes ischemic ventricular fibrillation in the rabbit heart
We show that calcium/calmodulin-dependent protein kinase II (CaMKII) blockade exacerbates intrinsically lower excitability in the right ventricular outflow tract, which causes highly nonuniform chamber-specific slowing of conduction and facilitates ventricular fibrillation during ischemia. Constitutive CaMKII activity is necessary for uniform and safe ventricular conduction, and CaMKII block is potentially proarrhythmic.
- Transcranial Doppler-determined change in posterior cerebral artery blood flow velocity does not reflect vertebral artery blood flow during exercise
We examined whether transcranial Doppler-determined flow velocity in the posterior cerebral artery can be used as an index of cerebral blood flow during exercise. However, the changes in posterior cerebral artery flow velocity during exercise do not reflect vertebral artery blood flow.
- Impaired peripheral vasodilation during graded systemic hypoxia in healthy older adults: role of the sympathoadrenal system
We found that the lack of peripheral vasodilation during graded systemic hypoxia with aging is not mediated by the sympathoadrenal system, strongly implicating local vascular control mechanisms in this impairment. Understanding these mechanisms may lead to therapeutic advances for improving tissue blood flow and oxygen delivery in aging and disease.
RESEARCH ARTICLES | Muscle Mechanics and Ventricular Function
- Peroxisome proliferator-activated receptor-α expression induces alterations in cardiac myofilaments in a pressure-overload model of hypertrophy
Data presented here demonstrate novel signaling to sarcomeric proteins by chronic alterations in fatty acid metabolism induced by PPARα. The mechanism involves modifications of key myofilament regulatory proteins modifying cross-bridge dynamics with differential effects in controls and hearts stressed by pressure overload.
- Why septal motion is a marker of right ventricular failure in pulmonary arterial hypertension: mechanistic analysis using a computer model
A novel approach describes the mechanism underlying abnormal septal dynamics in pulmonary arterial hypertension. Change in motion is not uniquely induced by altered right ventricular afterload, but also by altered ventricular relaxation dyssynchrony. Extension or change in motion is a marker reflecting interplay between right and left ventricular contractility.
RESEARCH ARTICLES | Vascular Biology and Microcirculation
- Atheroprotective vaccination with MHC-II-restricted ApoB peptides induces peritoneal IL-10-producing CD4 T cells
Vaccination against apolipoprotein B (ApoB), the protein of LDL, attracts attention as a novel approach to prevent atherosclerosis. We discovered major histocompatibility protein class II-restricted ApoB peptides, which reduce atherosclerosis and induce IL-10-producing CD4+ T cells and chemokine (C-C motif) receptor 5 expression on regulatory T cells, suggesting that immunization with ApoB peptides inhibits atherosclerosis by inducing anti-inflammatory cytokines.
- NFAT regulation of cystathionine γ-lyase expression in endothelial cells is impaired in rats exposed to intermittent hypoxia
This study identifies the calcium-regulated transcription factor nuclear factor of activated T cells as a novel regulator of cystathionine γ-lyase (CSE). This pathway is basally active in mesenteric artery endothelial cells, but, after exposure to intermittent hypoxia to mimic sleep apnea, nuclear factor of activated T cells c3 nuclear translocation and CSE expression are decreased, concomitant with decreased CSE-dependent vasodilation.
- Can endothelial hemoglobin-α regulate nitric oxide vasodilatory signaling?
Mathematical modeling shows that although regulation of nitric oxide signaling by hemoglobin-α (Hbα) is plausible, it is conditional to its presence in significant concentrations colocalized with endothelial nitric oxide synthase in myoendothelial projections. Additional experimentation is required to test that the strong effect of Hbα seen in vitro, translates into a physiologically relevant response in vivo.
RAPID REPORT | Vascular Biology and Microcirculation
- Influence of sex on microvascular and macrovascular responses to prolonged sitting
We demonstrate that leg macrovascular function was consistently reduced in young men but not young women after prolonged sitting. In contrast, both men and women exhibited similar reductions in leg microvascular reactivity after sitting. These data demonstrate, for the first time, sex differences in vascular responses to prolonged sitting.
- Evidence for hysteresis in the cerebral pressure-flow relationship in healthy men
The novel finding of this study is that the change in middle cerebral artery mean flow velocity is attenuated during hypertension compared with hypotension physiologically induced by oscillations in blood pressure in men. These results support that the human brain is more effective at compensating for transient hypertension than hypotension.