The role of macrophage transcription factor MafB in atherosclerotic plaque stability.

Background And Aims: Macrophage differentiation is associated with the development of atherosclerosis and plaque vulnerability and is regulated by transcription factor MafB. We previously reported that MafB attenuates macrophage apoptosis, which is associated with atherosclerotic plaque instability. The aim of this study was to elucidate the role of MafB in the progression of atherosclerotic plaque.

HECT-Type Ubiquitin E3 Ligase ITCH Interacts With Thioredoxin-Interacting Protein and Ameliorates Reactive Oxygen Species-Induced Cardiotoxicity.

Background: The homologous to the E6-AP carboxyl terminus (HECT)-type ubiquitin E3 ligase ITCH is an enzyme that plays a pivotal role in posttranslational modification by ubiquitin proteasomal protein degradation. Thioredoxin-interacting protein (TXNIP) is a negative regulator of the thioredoxin system and an endogenous reactive oxygen species scavenger. In the present study, we focused on the functional role of ubiquitin E3 ligase ITCH and its interaction with TXNIP to elucidate the mechanism of cardiotoxicity induced by reactive oxygen species, such as doxorubicin and hydrogen peroxide.

Heart-type fatty acid binding protein and high-sensitivity troponin T are myocardial damage markers that could predict adverse clinical outcomes in patients with peripheral artery disease.

Background: Despite many recent advances in endovascular therapy (EVT), peripheral artery disease (PAD) is an increasing health problem with high mortality. Heart-type fatty acid-binding protein (H-FABP) and high-sensitivity troponin T (hsTnT) are markers of ongoing myocardial damage and have been reported to be useful indicators of future cardiovascular events. However, it remains to be determined whether H-FABP and hsTnT can predict adverse clinical outcomes in patients with PAD.

Cystatin C-based eGFR is a superior prognostic parameter to creatinine-based eGFR in post-endovascular therapy peripheral artery disease patients.

Background: Kidney dysfunction is reportedly associated with adverse outcome in patients with peripheral artery disease (PAD). Estimated glomerular filtration rate (eGFR), a recently popularized index for assessing kidney function, is calculated using serum creatinine or cystatin C. Compared with creatinine-based eGFR (eGFRcr), cystatin C-based eGFR (eGFRcys) is less affected by age, gender, and muscle mass.

Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

Background: Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF.

Utility of the Japan arteriosclerosis longitudinal study score for identifying a high risk for vasospastic angina.

Objective: The aim of this study was to investigate whether the Japan Arteriosclerosis Longitudinal Study (JALS) score, which is calculated from the traditional atherosclerotic coronary risk, is associated with the incidence of coronary vasospasms.

Methods: We performed vasospasm provocation tests with acetylcholine in 109 patients referred to our hospital due to suspected vasospastic angina and subsequently calculated the atherosclerotic risk score according to the JALS score. Consequently, coronary vasospasms were evoked in 51 patients.

High-mobility group box 1-mediated heat shock protein beta 1 expression attenuates mitochondrial dysfunction and apoptosis.

Aims: Apoptosis of cardiomyocytes is thought to account for doxorubicin cardiotoxicity as it contributes to loss of myocardial tissue and contractile dysfunction. Given that high-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein capable of inhibiting apoptosis, we aimed to clarify the role of HMGB1 in heat shock protein beta 1 (HSPB1) expression during doxorubicin-induced cardiomyopathy.

Methods And Results: Mitochondrial damage, cardiomyocyte apoptosis, and cardiac dysfunction after doxorubicin administration were significantly attenuated in mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) compared with wild type (WT) -mice.

Sarcopenia evaluated by fat-free mass index is an important prognostic factor in patients with chronic heart failure.

Background And Aim: Chronic heart failure (CHF) is a major cause of morbidity and mortality, and cardiac cachexia and sarcopenia are serious complications associated with weight loss and increased catabolism. Fat-free mass index (FFMI) is an indicator of resting energy expenditure and is used for the clinical diagnosis of sarcopenia. In the present study, we investigated the impact of sarcopenia, as evaluated by FFMI, on cardiac prognosis in patients with CHF.

Deficiency of Long Pentraxin PTX3 Promoted Neointimal Hyperplasia after Vascular Injury.

Aim: Pentraxin 3 (PTX3) is a novel marker for the primary local activation of innate immunity and inflammatory responses. Although clinical and experimental evidence suggests that PTX3 is associated with atherosclerosis, the relationship between PTX3 and vascular remodeling after wall injury remains to be determined. We investigated the effects of PTX3 on neointimal hyperplasia following wire vascular injury.

A novel mouse model of aortic valve stenosis induced by direct wire injury.

Objective: The response-to-tissue-injury theory is currently the favorite paradigm to investigate valve pathology. To the best of our knowledge, there are currently no in vivo valve injury models. There are few calcific aortic valve stenosis (AVS) models that develop hemodynamically significant stenosis.

Electrocardiographic left ventricular hypertrophy Cornell product is a feasible predictor of cardiac prognosis in patients with chronic heart failure.

Background: Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular disease and is associated with heart failure development. The Cornell product is an easily measured electrocardiographic parameter for assessing LVH. However, it is undetermined whether the Cornell product can predict the cardiac prognosis of chronic heart failure (CHF) patients.

Midkine exacerbates pressure overload-induced cardiac remodeling.

Midkine is a multifunctional growth factor, and its serum levels are increased with the functional severity of heart failure. This study aimed to examine the role of midkine in heart failure pathogenesis. Midkine expression levels were increased in the kidney and lung after transverse aortic constriction (TAC) surgery, but not sufficiently increased in the heart.

Prognostic importance of objective nutritional indexes in patients with chronic heart failure.

Background: Although malnutrition indicates an unfavorable prognosis in some clinical settings, the association between nutritional indexes and outcomes for patients with chronic heart failure (CHF) is unclear.

Methods And Results: All the previously established objective nutritional indexes were evaluated. The controlling nutritional status score (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) were determined for 388 consecutive patients with CHF (mean age 69.

Atrial endothelial impairment through Toll-like receptor 4 signaling causes atrial thrombogenesis.

Low-grade inflammation associated with heart failure (HF) is known to deteriorate cardioembolic stroke in patients with atrial fibrillation (AF). Little is known about the relationship between atrial endothelial impairment induced by innate immunity and thrombus formation. We examined whether atrial endothelial impairment through Toll-like receptor (TLR) 4 signaling causes atrial thrombogenesis.

Diacylglycerol kinase α exacerbates cardiac injury after ischemia/reperfusion.

Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal for the preservation of myocardial function. However, reperfusion itself causes additional myocardium injuries. Activation of the diacylglycerol-protein kinase C (DAG-PKC) cascade has been implicated in the cardioprotective effects occurring after ischemia/reperfusion (I/R).

Cardiac nuclear high mobility group box 1 prevents the development of cardiac hypertrophy and heart failure.

Aims: High mobility group box 1 (HMGB1) is an abundant and ubiquitous nuclear DNA-binding protein that has multiple functions dependent on its cellular location. HMGB1 binds to DNA, facilitating numerous nuclear functions including maintenance of genome stability, transcription, and repair. However, little is known about the effects of nuclear HMGB1 on cardiac hypertrophy and heart failure.

The impact of renal tubular damage, as assessed by urinary β2-microglobulin-creatinine ratio, on cardiac prognosis in patients with chronic heart failure.

Background: Renal dysfunction was reported to be closely associated with clinical outcomes in patients with chronic heart failure (CHF). Renal tubulointerstitial damage has been shown to be an important factor in the development of renal dysfunction as well as glomerular damage. However, the impact of renal tubular damage on clinical outcomes in patients with CHF remains to be determined.

Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.

Background: Left ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3) is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload.

Acidic urine is associated with poor prognosis in patients with chronic heart failure.

Renal dysfunction is reported to be associated with poor outcomes in patients with chronic heart failure (CHF). A recent study showed that acidic urine is related to chronic kidney disease, which is a risk factor for the development of CHF. However, it remains to be determined whether acidic urine is associated with poor outcomes in patients with CHF.

Renal tubulointerstitial damage is associated with short-term cardiovascular events in patients with myocardial infarction.

Background: Urinary β2 microglobulin (U-β2MG) is a more sensitive and accurate marker of tubulointerstitial damage. The etiology of glomerular damage is related to the occurrence of major adverse cardiovascular events (MACE) in patients with myocardial infarction (MI); however, the prognostic importance of tubulointerstitial damage in patients with ST-segment elevation MI (STEMI) has not been established. The aim of this study was to elucidate whether renal tubulointerstitial damage is associated with the occurrence of MACE in patients after STEMI undergoing percutaneous coronary intervention.

Serum pregnancy-associated plasma protein a in patients with heart failure.

Background: Pregnancy-associated plasma protein A (PAPP-A) proteolyzes insulin-like growth factor (IGF)-binding proteins and thus increases IGF-1 bioactivity. PAPP-A has been reported to be involved in various pathophysiologic abnormalities; however, the clinical significance of PAPP-A has not been examined in cases of heart failure (HF). We hypothesized that PAPP-A levels might be correlated with the severity of HF.

Elevated cystatin C levels predict the incidence of vasospastic angina.

Background: Cystatin C, a marker for early stage chronic kidney disease, has been shown to be involved in cardiovascular disease. The relationship between serum cystatin C levels and coronary vasospastic angina (VSA), however, remains to be elucidated. The aim of the present study was to investigate whether elevated cystatin C levels predict the incidence of VSA.

Iodine-123-metaiodobenzylguanidine imaging can predict future cardiac events in heart failure patients with preserved ejection fraction.

Objective: Iodine-123-metaiodobenzylguanidine ((123)I-MIBG) has been used to assess the function of the cardiac sympathetic nervous system in patients with chronic heart failure (HF). The usefulness of (123)I-MIBG imaging for evaluating patients with heart failure with preserved ejection fraction (HFPEF) has not been established.

Methods: We performed (123)I-MIBG scintigraphy and echocardiography and measured the plasma brain natriuretic peptide (BNP) levels of 117 consecutive HF patients (64 men, mean age 66 ± 14 years) with a left ventricular ejection fraction (LVEF) of ≥50% who were admitted to our hospital.