In this Issue
May 2017; volume 312, issue 5
REVIEW | Guidelines in Cardiovascular Research
REVIEWS | Inflammation, Immunity, and Cardiovascular Disease
RESEARCH ARTICLE | Cardiovascular Actions of Hydrogen Sulfide and Other Gasotransmitters
- Hydrogen sulfide alleviates hypertensive kidney dysfunction through an epigenetic mechanism
We investigated epigenetic changes that occur in the hypertensive kidney and how H2S supplementation reverses adverse effects. Inflammation, aberrant methylation, and dysfunction were observed in the hypertensive kidney, and these effects were alleviated with H2S supplementation. We identify miR-129 as a potential regulator of blood pressure and H2S regulation.
RESEARCH ARTICLE | Cardiovascular Neurohormonal Regulation
- A novel role for miR-133a in centrally mediated activation of the renin-angiotensin system in congestive heart failure
Angiotensinogen (AGT) expression is upregulated in the paraventricular nucleus of the hypothalamus through posttranscriptional mechanism interceded by microRNA-133a in heart failure. Understanding the mechanism of increased expression of AGT in pathological conditions leading to increased sympathoexcitation may provide the basis for the possible development of new therapeutic agents with enhanced specificity.
RESEARCH ARTICLE | Heart Failure: Novel Therapeutic Pathways Emerging from Basic Science
- Angiotensin-(1–7) attenuates angiotensin II-induced cardiac hypertrophy via a Sirt3-dependent mechanism
Chronic subcutaneous ANG-(1–7) has no effect on ANG II-induced elevations in blood pressure but significantly attenuates ANG II-induced cardiac hypertrophy and fibrosis by a mitochondrial ROS-dependent mechanism. This protective effect of ANG-(1–7) against the action of ANG II action is mediated by stimulation of sirtuin-3-mediated deacetylation of FoxO3a, which triggers SOD2 expression.
RESEARCH ARTICLES | Integrative Cardiovascular Physiology and Pathophysiology
- Mild hypothermia preserves myocardial conduction during ischemia by maintaining gap junction intracellular communication and Na+ channel function
Therapeutic hypothermia is now a class I recommendation for resuscitation from cardiac arrest. This study determined that hypothermia preserves gap junction coupling as well as Na+ channel function during acute cardiac ischemia, attenuating conduction slowing and preventing conduction block, suggesting that induced hypothermia may be a novel antiarrhythmic strategy in resuscitation.
- Short-term regular aerobic exercise reduces oxidative stress produced by acute high intraluminal pressure in the adipose microvasculature
We describe potential mechanisms contributing to aerobic exercise-conferred protection against high intravascular pressure. Subcutaneous adipose microvessels from exercise mice express less NADPH oxidase (NOX) II and more superoxide dismutase (SOD) and demonstrate less sensitivity to ANG II. In microvascular endothelial cells, shear stress reduced NOX II but did not influence SOD expression.
- ERBB signaling attenuates proinflammatory activation of nonclassical monocytes
This study identified a novel role of neuregulin-1 (NRG-1)/ERBB signaling in the control of proinflammatory activation of monocytes. These results further improve our fundamental understanding of cardioprotective effects of NRG-1 in patients with heart failure.
- Temporal dissociation between the minimal distal-to-aortic pressure ratio and peak hyperemia during intravenous adenosine infusion
Systemic hemodynamic variability during intravenous adenosine infusion produces substantial temporal dissociation between peak hyperemia appraised by coronary flow velocity and the minimal distal-to-aortic pressure ratio commonly used to determine functional stenosis severity. This dissociation was absent for intracoronary adenosine administration and tended to be mitigated in patients receiving Ca2+ antagonists.
- High-throughput screening identifies microRNAs that target Nox2 and improve function after acute myocardial infarction
NADPH oxidase (Nox)2 is a promising target for treating cardiovascular disease, but there are no specific inhibitors. Finding endogenous signals that can target Nox2 and other inflammatory molecules is of great interest. In this study, we used high-throughput screening to identify microRNAs that target Nox2 and improve cardiac function after infarction.
- Cardiovascular consequences of the inspiratory muscle metaboreflex: effects of age and sex
Premenopausal women exhibit an attenuated inspiratory muscle metaboreflex compared with young men; however, it is unknown whether these sex differences are present in older adults. Older women exhibited a greater inspiratory muscle metaboreflex compared with premenopausal women, whereas no differences were present between older and younger men.
- Microvascular leakage in acute myocardial infarction: characterization by histology, biochemistry, and magnetic resonance imaging
We characterized, for the first time, the features of microvascular leakage (MVL) as a consequence of reperfused myocardial infarction. The size of ischemic myocardium exhibiting MVL was significantly greater than that of infarction or no reflow. We made a proof-of-concept finding on the diagnostic potential of MVL by cardiac magnetic resonance imaging.
- Impact of mild orthostatic stress on aortic-cerebral hemodynamic transmission: insight from the frequency domain
We characterized the pulsatile hemodynamic transmission from the heart to the brain by frequency-domain analysis. The low-frequency transmission was augmented with a mild LBNP stimulation partly due to the elevated systemic vascular resistance. A systemic vasoconstriction deteriorates the dampening effect on slow oscillations of pulsatile hemodynamics toward the brain.
RESEARCH ARTICLES | Muscle Mechanics and Ventricular Function
- Noninvasive stratification of postinfarction rats based on the degree of cardiac dysfunction using magnetic resonance imaging and echocardiography
In vivo phenotyping of rats is essential for robust and reliable data. Here, we present two simple noninvasive schemes for the stratification of postinfarction rats based on the degree of heart failure: one using magnetic resonance imaging and one based on echocardiography.
- Sept7b is required for the subcellular organization of cardiomyocytes and cardiac function in zebrafish
Knockdown of the zebrafish ortholog of human septin 7 (sept7b) destabilizes cardiac actin and reduces ventricular dimensions, contractility, and cardiac output in larval zebrafish, indicating that sept7b is essential for cardiac function. We further found that sept7b and retinoic acid signaling pathways converge to regulate cardiac function. These data prompt further studies defining the role of sept7b in cardiomyopathies.
RESEARCH ARTICLES | Vascular Biology and Microcirculation
- Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions
We report the first direct in vivo evidence that a smooth muscle cell (SMC)-produced collagen, collagen type XV (COL15A1), is critical for atherosclerotic lesion development. SMC Col15a1 knockout markedly attenuated advanced lesion formation, likely through reducing SMC proliferation and impairing multiple proatherogenic inflammatory processes.
- Mitochondria-regulated formation of endothelium-derived extracellular vesicles shifts the mediator of flow-induced vasodilation
The vascular effect of endothelium-derived extracellular vesicles (eEVs) is biphasic, with higher doses decreasing the magnitude of flow-induced dilation (FID) compared with lower doses that shift the mediator of FID from nitric oxide to H2O2. eEVs may cause vascular dysfunction via similar pathways despite being formed from different stimuli, although both require mitochondrial reactive oxygen species for their formation.
INNOVATIVE METHODOLOGY | Integrative Cardiovascular Physiology and Pathophysiology
- A novel method of standardized myocardial infarction in aged rabbits
This study describes the coronary angiographic imaging of young and aged rabbits. We developed and improved a novel minimally invasive approach for coil embolization that targets a specific area of myocardium and yielded a consistent scar encompassing ~30% of the left ventricular free wall of young and aged rabbit hearts.
INNOVATIVE METHODOLOGY | Vascular Biology and Microcirculation
- Ultrasound detection of altered placental vascular morphology based on hemodynamic pulse wave reflection
Here, we describe a novel approach to noninvasively detect microvascular changes in the fetoplacental circulation using ultrasound. The technique is based on detecting reflection pulse pressure waves that travel along the umbilical artery. Using a proof-of-principle study, we demonstrate the feasibility of the technique in two strains of experimental mice.