Cytokine mRNA Degradation in Cardiomyocytes Restrains Sterile Inflammation in Pressure-Overloaded Hearts.

Background: Proinflammatory cytokines play an important role in the pathogenesis of heart failure. The mechanisms responsible for maintaining sterile inflammation within failing hearts remain poorly defined. Although transcriptional control is important for proinflammatory cytokine gene expression, the stability of mRNA also contributes to the kinetics of immune responses.

FKBP8 protects the heart from hemodynamic stress by preventing the accumulation of misfolded proteins and endoplasmic reticulum-associated apoptosis in mice.

Protein quality control in cardiomyocytes is crucial to maintain cellular homeostasis. The accumulation of damaged organelles, such as mitochondria and misfolded proteins in the heart is associated with heart failure. During the process to identify novel mitochondria-specific autophagy (mitophagy) receptors, we found FK506-binding protein 8 (FKBP8), also known as FKBP38, shares similar structural characteristics with a yeast mitophagy receptor, autophagy-related 32 protein.

Toll-like receptor 9 prevents cardiac rupture after myocardial infarction in mice independently of inflammation.

We have reported that the Toll-like receptor 9 (TLR9) signaling pathway plays an important role in the development of pressure overload-induced inflammatory responses and heart failure. However, its role in cardiac remodeling after myocardial infarction has not been elucidated. TLR9-deficient and control C57Bl/6 wild-type mice were subjected to left coronary artery ligation.

Glucocorticoids Induce Cardiac Fibrosis via Mineralocorticoid Receptor in Oxidative Stress: Contribution of Elongation Factor Eleven-Nineteen Lysine-Rich Leukemia (ELL).

Background: Cardiac fibrosis is considered to be a crucial factor in the development of heart failure. Blockade of the mineralocorticoid receptor (MR) attenuated cardiac fibrosis and improved the prognosis of patients with chronic heart failure but the ligand for MR and the regulatory mechanism of MR pathway in the diseased heart are unclear. Here, we investigated whether glucocorticoids can promote cardiac fibrosis through MR in oxidative stress and the involvement of elongation factor eleven-nineteen lysine-rich leukemia (ELL), a co-activator of MR, in this pathway.

Endovascular aortic repair increases vascular stiffness and alters cardiac structure and function.

Background: Endovascular aortic repair (EVAR) is performed in patients with thoracic or abdominal aortic aneurysm because it is less invasive than conventional open repair. However, the effects of EVAR on vascular and cardiac function remain to be clarified.

Methods And Results: We studied the effects of EVAR on several outcome variables in 40 consecutive patients undergoing EVAR for abdominal and/or thoracic aneurysm with preserved ejection fraction.

A novel heart failure mice model of hypertensive heart disease by angiotensin II infusion, nephrectomy, and salt loading.

Although the mouse heart failure (HF) model of hypertensive heart disease (HHD) is useful to investigate the pathophysiology and new therapeutic targets for HHD, the model using simple experimental procedures and stable phenotypes has not been established. This study aimed to develop a novel mouse HF model of HHD by combining salt loading and uninephrectomy with ANG II infusion. Eight-week-old C57BL/6 male mice were treated with ANG II infusion (AT), ANG II infusion and uninephrectomy (AN), ANG II infusion and salt loading (AS), or ANG II infusion, uninephrectomy, and salt loading (ANS).

Interleukin-16 promotes cardiac fibrosis and myocardial stiffening in heart failure with preserved ejection fraction.

Background: Chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction (HFpEF) is observed in half of all patients with CHF and carries the same poor prognosis as CHF with reduced LV ejection fraction (HFrEF). In contrast to HFrEF, there is no established therapy for HFpEF. Chronic inflammation contributes to cardiac fibrosis, a crucial factor in HFpEF; however, inflammatory mechanisms and mediators involved in the development of HFpEF remain unclear.

L-Carnitine prevents the development of ventricular fibrosis and heart failure with preserved ejection fraction in hypertensive heart disease.

Objectives: Prognosis of heart failure with preserved ejection fraction (HFpEF) remains poor because of unknown pathophysiology and unestablished therapeutic strategy. This study aimed to identify a potential therapeutic intervention for HFpEF through metabolomics-based analysis.

Methods And Results: Metabolomics with capillary electrophoresis time-of-flight mass spectrometry was performed using plasma of Dahl salt-sensitive rats fed high-salt diet, a model of hypertensive HFpEF, and showed decreased free-carnitine levels.

Diabetic retinopathy is associated with impaired left ventricular relaxation.

Background: Diabetic retinopathy (DR) is an independent predictor of heart failure (HF) in patients with diabetes mellitus (DM). However, it is unclear how DR is related to the development of HF. We hypothesized that DR is associated with left ventricular (LV) diastolic dysfunction, which is well recognized to subsequently result in HF.

Patients with more coronary yellow plaques have higher risk of stenosis progression within 7 months.

Background: Disruption of vulnerable plaques causes acute coronary syndrome and stenosis progression. Yellow plaques are regarded as vulnerable and the number of yellow plaques per vessel (NYP) has been reported as a marker of vulnerable patients. Therefore, we examined if patients with more yellow plaques would have higher risk of stenosis progression.

Ca2+ entry mode of Na+/Ca2+ exchanger as a new therapeutic target for heart failure with preserved ejection fraction.

Aims: Left ventricular (LV) fibrosis and stiffening play crucial roles in the development of heart failure with preserved ejection fraction (HFPEF). Plasma level of digitalis-like factors (DLFs) is increased in patients with hypertension, a principal underlying cardiovascular disease of HFPEF. Digitalis-like factors inhibit ion-pumping function of Na(+)/K(+)-ATPase and activate the Ca(2+) entry mode of Na(+)/Ca(2+) exchanger (NCX).

Competing risks of heart failure with preserved ejection fraction in diabetic patients.

Aims: The prevalence of heart failure with preserved ejection fraction (HFpEF) has increased in the past two decades, and diabetes mellitus (DM) is frequently associated with HFpEF. Although it has been demonstrated that left ventricular (LV) diastolic and vascular functional abnormalities are generally observed in HFpEF, it remains to be clinically elucidated how an asymptomatic stage progresses to symptomatic HFpEF in DM patients. We aimed to identify risk factors associated with incident HFpEF in DM patients and to evaluate the contribution of LV relaxation and compliance to the development of HFpEF.

Transition from asymptomatic diastolic dysfunction to heart failure with preserved ejection fraction: roles of systolic function and ventricular distensibility.

Background: Systolic abnormality, as well as diastolic dysfunction, is observed in patients with heart failure with preserved ejection fraction (HFPEF). However, the role of these 2 conditions in the transition from asymptomatic diastolic dysfunction to symptomatic heart failure remains unclear. We recently demonstrated that diastolic wall strain (DWS) inversely correlates to the myocardial stiffness constant.

Detecting of coronary dissection by coronary magnetic resonance.

A 75-year-old man, who had a history of coronary dissection after percutaneous coronary intervention in left anterior descending coronary artery, underwent coronary magnetic resonance. Magnetic resonance demonstrated coronary dissection in the distal portion of the left anterior descending artery. Both the true lumen with thick vessel wall and the false lumen with thin vessel wall were demonstrated in the cross-sectional images using T1-weighed black blood technique and T2-weighed black blood technique.

Evaluation of the cavotricuspid isthmus and right atrium by multidetector-row computed tomography in patients with common atrial flutter.

The sizes of the right atrium (RA), cavotricuspid isthmus, and Eustachian valve are predictors of success of radiofrequency catheter ablation for atrial flutter (AFL). We examined the relationship between the sizes of cavotricuspid isthmus as measured by multidetector-row computed tomography (MDCT) and fluoroscopy. We used eight-detector MDCT to measure the tricuspid isthmus of 23 patients prior to linear ablation for common AFL.