In this Issue
March 2017; volume 312, issue 3
REVIEW | Inflammation, Immunity, and Cardiovascular Disease
RESEARCH ARTICLE | Advances in Cardiovascular Geroscience
- Transgenic overexpression of macrophage matrix metalloproteinase-9 exacerbates age-related cardiac hypertrophy, vessel rarefaction, inflammation, and fibrosis
The present study was the first to use mice with transgenic overexpression of matrix metalloproteinase-9 (MMP-9) in macrophages to examine the effects of macrophage-derived MMP-9 on cardiac aging. We found that an elevation in macrophage-derived MMP-9 induced a greater age-dependent cardiac hypertrophy and vessel rarefaction phenotype, which enhanced cardiac inflammation and fibrosis.
RESEARCH ARTICLES | Cardiac Excitation and Contraction
- Reduced density and altered regulation of rat atrial L-type Ca2+ current in heart failure
Whole cell recording of L-type Ca2+ currents in atrial myocytes from rat hearts subjected to coronary artery ligation compared with those from sham-operated controls reveals marked reduction in current density in heart failure without change in channel subunit expression and associated with altered phosphorylation independent of protein kinase A.
- Cardiac sympathetic innervation via middle cervical and stellate ganglia and antiarrhythmic mechanism of bilateral stellectomy
Sympathetic activation in myocardial infarction leads to arrhythmias and worsens heart failure. Bilateral cardiac sympathetic denervation reduces ventricular tachycardia/ventricular fibrillation inducibility and mitigates effects of sympathetic activation on dispersion of repolarization and T-peak to T-end interval in infarcted hearts. Hemodynamic stability is maintained, as innervation via the middle cervical ganglion is not interrupted.
- Kvβ1.1 (AKR6A8) senses pyridine nucleotide changes in the mouse heart and modulates cardiac electrical activity
Cardiac electrical activity is mediated by ion channels, and Kv4.2 plays a significant role, along with its binding partner, the Kvβ1.1 subunit. In the present study, we identify Kvβ1.1 as a sensor of pyridine nucleotides changes and modulator of Kv4.2 gating, action potential duration, and ECG in the mouse heart.
- Effect of anisotropy on ventricular vulnerability to unidirectional block and reentry by single premature stimulation during normal sinus rhythm in rat heart
We performed ventricular cathodal point stimulation during sinus rhythm by progressively increasing stimulus strength and prematurity. Virtual electrode polarization and recovery gradient progressively induced make, break, and graded-response stimulation mechanisms. Unidirectional conduction block occurred along or across fiber direction, initiating figure-eight or spiral wave reentry, respectively, and tachycardia sustained by scroll wave and focal activations.
RESEARCH ARTICLES | Cardiovascular Actions of Hydrogen Sulfide and Other Gasotransmitters
- The interaction of estrogen and CSE/H2S pathway in the development of atherosclerosis
Female cystathionine γ-lyase (CSE)-knockout mice have significantly lower plasma estrogen levels and more severe early atherosclerotic lesion than female wild-type mice. H2S production in liver and vascular tissues is enhanced by estrogen via its stimulatory effect on CSE activity. The antiatherosclerotic effect of estrogen is mediated by CSE-generated H2S.
- The fate of sulfate in chronic heart failure
Sulfate clearance is decreased in chronic heart failure patients compared with healthy individuals. Among patients, sulfate clearance is positively associated with favorable disease outcome, i.e., a decreased rehospitalization rate and increased patient survival. Hence, decreased sulfate clearance may be involved in the pathophysiology of heart failure.
RESEARCH ARTICLES | Cardiovascular Neurohormonal Regulation
- Association of serum HMGB2 level with MACE at 1 mo of myocardial infarction: Aggravation of myocardial ischemic injury in rats by HMGB2 via ROS
We demonstrate that serum high-mobility group box 2 is associated with major adverse cardiac events at 1 mo in myocardial infarction patients. Mechanistically, high-mobility group box 2 promotes reactive oxygen species production via receptor for advanced glycation end products signaling in ischemic myocardium, thereby aggravating cell apoptosis, inflammation, and autophagosome clearance impairment. This study reveals that high-mobility group box 2 is a novel factor enhancing ischemic injury in myocardial infarction.
- Sympathetic modulation of electrical activation in normal and infarcted myocardium: implications for arrhythmogenesis
This study demonstrates regional control of conduction velocity in normal hearts by sympathetic nerves. In infarcted hearts, however, not only is modulation of propagation heterogeneous, some regions showed paradoxical conduction slowing. Sympathoexcitation altered propagation in all infarcted hearts studied, and we describe the temporal arrhythmogenic potential of these findings.
RESEARCH ARTICLES | Integrative Cardiovascular Physiology and Pathophysiology
- Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice
MasR deficiency abolishes protection of female mice from obesity-induced hypertension. Male MasR-deficient obese mice have reduced blood pressure and declines in cardiac function. ANG-(1–7) infusion restores obesity-induced cardiac dysfunction of wild-type, but not MasR-deficient, male mice. MasR agonists may be cardioprotective in obese males and females.
- The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics
Although multiscale entropy (MSE) and detrended fluctuation analysis (DFA) are recognizably useful prognostic/diagnostic methods, their physiological interpretation remains unclear. The present study clarifies the effect of the cardiac autonomic control on MSE and DFA, assessed during long periods (1 h). These findings are important to help the interpretation of future studies.
- Ischemic preconditioning in pigs: a causal role for signal transducer and activator of transcription 3
In pig hearts in situ, ischemic preconditioning (IPC) causally involves increased phosphorylation of STAT3, whereas Akt and ERK1/2 play no role for cardioprotection. The cardioprotective signal transduction of IPC is similar to that of IPC and remote IPC in pigs.
- Genetic determination of the vascular reactions in humans in response to the diving reflex
Our study demonstrates that the vascular reactions in response to the diving reflex are genetically determined and depend on gene polymorphisms of the kinin-bradykinin and the renin-angiotensin systems.
- Blood flow patterns underlie developmental heart defects
Congenital heart defects result from genetic anomalies, teratogen exposure, and altered blood flow during embryonic development. We show here a novel “dose-response” type relationship between the level of blood flow alteration and manifestation of specific cardiac phenotypes. We speculate that abnormal blood flow may frequently underlie congenital heart defects.
RESEARCH ARTICLES | Signaling and Stress Response
- Fluid shear stress induces upregulation of COX-2 and PGI2 release in endothelial cells via a pathway involving PECAM-1, PI3K, FAK, and p38
In this study we determined the major mechanotransduction pathway by which blood flow-driven shear stress activates cyclooxygenase-2 (COX-2) and prostaglandin I2 (PGI2) release in endothelial cells. Our work has demonstrated for the first time that COX-2/PGI2 mechanotransduction is mediated by the mechanosensor platelet endothelial cell adhesion molecule-1 (PECAM-1).
- Caveolae-specific activation loop between CaMKII and L-type Ca2+ channel aggravates cardiac hypertrophy in α1-adrenergic stimulation
While signaling in caveolae is thought to be important in cardiac hypertrophy, direct evidence is missing due to lack of tools to assess caveolae-specific signaling. This is the first study to demonstrate caveolae-specific activation of CaMKII signaling in cardiac hypertrophy induced by α1-adrenergic stimulation using an originally developed tool.
RESEARCH ARTICLES | Vascular Biology and Microcirculation
- Dynamin-related protein 1 mediates low glucose-induced endothelial dysfunction in human arterioles
Acute low-glucose exposure induces mitochondrial fragmentation in endothelial cells via Drp1 and is associated with impaired endothelial function in human arterioles. Targeting of Drp1 prevents fragmentation, improves vasofunction, and may provide a therapeutic target for improving cardiovascular complications among diabetics.
- Elevated 20-HETE impairs coronary collateral growth in metabolic syndrome via endothelial dysfunction
Elevated 20-hydroxyeicosatetraenoic acid (20-HETE) impairs coronary collateral growth (CCG) in metabolic syndrome by eliciting endothelial dysfunction and apoptosis via excessive neutrophil infiltration. 20-HETE antagonists completely restore coronary collateral growth in metabolic syndrome. microRNA-145 (miR-145) is an upstream regulator of 20-HETE production in metabolic syndrome; low expression of miR-145 in metabolic syndrome promotes elevated production of 20-HETE.
- The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis
Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN.