HOPX-associated molecular programs control cardiomyocyte cell states underpinning cardiac structure and function.

Genomic regulation of cardiomyocyte differentiation is central to heart development and function. This study uses genetic loss-of-function human-induced pluripotent stem cell-derived cardiomyocytes to evaluate the genomic regulatory basis of the non-DNA-binding homeodomain protein HOPX. We show that HOPX interacts with and controls cardiac genes and enhancer networks associated with diverse aspects of heart development.

Generation of Conditional Knockout Zebrafish Using an Invertible Gene-Trap Cassette.

Conditional knockout (cKO) is a genetic technique to inactivate gene expression in specific tissues or cell types in a temporally regulated manner. cKO analysis is essential to investigate gene function while avoiding the confounding effects of global gene deletion. Genetic techniques enabling cKO analysis were developed in mice based on culturable embryonic stem cells that were not generally available in zebrafish, which hampered precise analysis of genetic mechanisms of organ development and regeneration.

Zebrafish Is Necessary for Normal Development and Macrophage Migration.

Heme oxygenase function is highly conserved between vertebrates where it plays important roles in normal embryonic development and controls oxidative stress. Expression of the zebrafish heme oxygenase 1 genes is known to be responsive to oxidative stress suggesting a conserved physiological function. In this study, we generate a knockout allele of zebrafish and characterize the effects of and loss on embryonic development.

Platelet derived growth factor-A (Pdgf-a) gene transfer modulates scar composition and improves left ventricular function after myocardial infarction.

Background: Novel therapies that can limit or reverse damage caused by myocardial infarction (MI) could ease the increasing burden of heart failure. In this regard Platelet Derived Growth Factor (PDGF) has been previously shown to contribute to cardiac repair after MI. Here, we use a rodent model of MI and recombinant adeno-associated virus 9 (rAAV9)-mediated gene transfer to overexpress Pdgf-a in the injured heart and assess its therapeutic potential.

Krüppel-like factor 1 is a core cardiomyogenic trigger in zebrafish.

Cardiac regeneration requires dedifferentiation and proliferation of mature cardiomyocytes, but the mechanisms underlying this plasticity remain unclear. Here, we identify a potent cardiomyogenic role for Krüppel-like factor 1 (Klf1/Eklf), which is induced in adult zebrafish myocardium upon injury. Myocardial inhibition of Klf1 function does not affect heart development, but it severely impairs regeneration.

Vitamin D Improves Cardiac Function After Myocardial Infarction Through Modulation of Resident Cardiac Progenitor Cells.

Background: Vitamin D has been implicated in the prevention of heart failure. However the underlying mechanism remains unclear. We hypothesised that these effects may be partially mediated by cardiac stem/progenitor cells (CPCs).

Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice.

Chronic hypertension causes vascular remodeling that is associated with an increase in periostin- (postn) positive cells, including fibroblasts and smooth muscle cells. Krüppel-like factor (KLF) 5, a transcription factor, is also observed in vascular remodeling; however, it is unknown what role KLF5 plays in postn-positive cells during vascular remodeling induced by deoxycorticosterone-acetate (DOCA) salt. We used postn-positive cell-specific Klf5-deficient mice (Klf5KO: Klf5; Postn) and wild-type mice (WT: Klf5; Postn).

Suppression of murine autoimmune myocarditis achieved with direct renin inhibition.

Background: The renin angiotensin system (RAS) plays an important role in the pathogenesis of cardiovascular diseases and inflammation. Myocarditis is an inflammatory disease of the heart, and the role of the RAS in its pathophysiology is unknown. Because the direct renin inhibitor, aliskiren, is thought to block RAS completely, we investigated the cardioprotective effect of aliskiren in mice with experimental autoimmune myocarditis (EAM).

A different role of angiotensin II type 1a receptor in the development and hypertrophy of plantaris muscle in mice.

The role of angiotensin II type 1 (AT1) receptors in muscle development and hypertrophy remains unclear. This study was designed to reveal the effects that a loss of AT1 receptors has on skeletal muscle development and hypertrophy in mice. Eight-week-old male AT1a receptor knockout (AT1a(-/-)) mice were used for this experiment.

A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice.

Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases.

A P2X7 receptor antagonist attenuates experimental autoimmune myocarditis via suppressed myocardial CD4+ T and macrophage infiltration and NADPH oxidase 2/4 expression in mice.

Myocarditis is a clinically serious disease; however, no effective treatment has been elucidated. The P2X7 receptor is related to the pathophysiology of inflammation in many cardiovascular diseases. The P2X7 receptor antagonist is promising as an immunosuppressive treatment; however, its role in myocarditis is still to be established.

The periodontal pathogen Aggregatibacter actinomycetemcomitans affects experimental autoimmune myocarditis in mice.

Recent reports assert that dental health is linked to an increased risk of cardiovascular disease. It is well known that Aggregatibacter actinomycetemcomitans (A.a.

Neovascularization induced by hypoxia inducible transcription factor is associated with the improvement of cardiac dysfunction in experimental autoimmune myocarditis.

Objective: Mechanisms of cardiac dysfunction in myocarditis have not been fully elucidated. Though it remains controversial whether angiogenesis is beneficial or harmful in inflammatory disease, significant vascular destruction might possibly impair cardiac function in myocarditis. The prolyl hydroxylase domain-containing protein (PHD) inhibitor is a potential drug for promoting angiogenesis as it stabilizes hypoxia inducible transcription factor (HIF).

Inhibition of NF-κB activation by a novel IKK inhibitor reduces the severity of experimental autoimmune myocarditis via suppression of T-cell activation.

NF-κB, which is activated by the inhibitor of NF-κB kinase (IKK), is involved in the progression of inflammatory disease. However, the effect of IKK inhibition on the progression of myocarditis is unknown. We examined the effect of IKK inhibition on the progression of myocarditis.

Porphyromonas gingivalis promotes neointimal formation after arterial injury through toll-like receptor 2 signaling.

We previously demonstrated that Porphyromonas gingivalis infection induces neointimal hyperplasia with an increase in monocyte chemoattractant protein (MCP)-1 after arterial injury in wild-type mice. Toll-like receptor (TLR) 2 is a key receptor for the virulence factors of P. gingivalis.

A selective peroxisome proliferator-activated receptor-β/δ agonist attenuates neointimal hyperplasia after wire-mediated arterial injury.

Background: Neointimal hyperplasia after the percutaneous coronary intervention is still a clinically serious problem, associated with the risk of thrombosis due to delayed reendothelization. Peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) belongs to a family of ligand-activated transcription factors.

Objectives: In this study, we investigated the effects of GW-0742, a synthetic high-affinity PPAR-β/δ agonist, on neointimal hyperplasia after arterial injury.

Anti-salusin-β antibody enhances angiogenesis after myocardial ischemia reperfusion injury.

Backgrounds: Salusins are multifunctional endogenous bioactive peptides simultaneously biosynthesized from their precursor prosalusin. Salusin-β stimulates proliferation of vascular smooth muscle cells and fibroblasts and regulates myocardial growth and hypertrophy. Salusin-β has potent hypotensive, bradycardic and proatherosclerotic effects.

Chlorogenic acid attenuates ventricular remodeling after myocardial infarction in mice.

Chlorogenic acid (CGA), which is a key component of coffee, has many biological effects such as anti-inflammation activity. However, the effects of CGA on ventricular remodeling after myocardial ischemia have not been well investigated. To test the hypothesis that CGA can attenuate chronic ventricular remodeling after myocardial ischemia, we orally administered CGA to murine myocardial ischemia models.

Toll-like receptor-2 plays a fundamental role in periodontal bacteria-accelerated abdominal aortic aneurysms.

Background:  Periodontopathic bacteria are detected at a high rate in specimens obtained from the aortic walls of patients with abdominal aortic aneurysm (AAA) and are involved in AAA development. The purpose of this study was to clarify the role of Toll-like receptors (TLRs), which are key receptors of virulence factors of many periodontal bacteria, on periodontopathic bacteria-accelerated AAA progression.

Methods And Results:  AAA was produced by peri-aortic application of 0.

Periodontal bacteria aggravate experimental autoimmune myocarditis in mice.

Periodontitis is one of the most common infections in humans. Recently, published reports assert that periodontitis is associated with cardiovascular disease. Although it is said that viral, bacterial infections and autoimmune diseases may be the cause of myocarditis, the pathogenesis of it remains unclear.

Inhibition of IκB phosphorylation prevents load-induced cardiac dysfunction in mice.

Pressure overload is known to be a cause of cardiac hypertrophy that often transits to heart failure. Although nuclear factor (NF)-κB is a key factor in the progression of cardiac hypertrophy, its pathophysiology is yet to be elucidated. Thus, we aimed to show that inhibition of NF-κB activation improves pressure overload-induced cardiac dysfunction.

Periodontal pathogen Aggregatibacter actinomycetemcomitans deteriorates pressure overload-induced myocardial hypertrophy in mice.

Although a relationship between periodontitis and myocardial hypertrophy has been reported, the precise mechanism has not been clarified. The purpose of this study was to investigate the association between periodontal infection and myocardial hypertrophy. Transverse aortic constriction (TAC) was performed.

Impaired post-infarction cardiac remodeling in chronic kidney disease is due to excessive renin release.

The complex pathophysiological interactions between heart and kidney diseases are collectively known as cardiorenal syndrome. The renin-angiotensin system (RAS) may have a pivotal role in the development of cardiorenal syndrome. The aim of this study was to elucidate the RAS activity responsible for adverse post-infarction remodeling and prognosis in mice with renal failure.

The periodontal pathogen Aggregatibacter actinomycetemcomitans deteriorates ventricular remodeling after myocardial infarction in mice.

Chronic inflammation plays a fundamental role in coronary heart disease (CHD). Periodontal disease is a common infectious disease and is a potential source of systemic inflammation. However, the effect of periodontal infection on CHD has not yet been proven.