Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading.

Cardiac hypertrophy occurs in response to a variety of stresses as a compensatory mechanism to maintain cardiac output and normalize wall stress. Prevention or regression of cardiac hypertrophy can be a major therapeutic target. Although regression of cardiac hypertrophy occurs after control of etiological factors, the molecular mechanisms remain to be clarified.

Rheb (Ras homologue enriched in brain)-dependent mammalian target of rapamycin complex 1 (mTORC1) activation becomes indispensable for cardiac hypertrophic growth after early postnatal period.

Cardiomyocytes proliferate during fetal life but lose their ability to proliferate soon after birth and further increases in cardiac mass are achieved through an increase in cell size or hypertrophy. Mammalian target of rapamycin complex 1 (mTORC1) is critical for cell growth and proliferation. Rheb (Ras homologue enriched in brain) is one of the most important upstream regulators of mTORC1.

Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure.

Heart failure is a leading cause of morbidity and mortality in industrialized countries. Although infection with microorganisms is not involved in the development of heart failure in most cases, inflammation has been implicated in the pathogenesis of heart failure. However, the mechanisms responsible for initiating and integrating inflammatory responses within the heart remain poorly defined.

Calpain protects the heart from hemodynamic stress.

Calpains make up a family of Ca(2+)-dependent intracellular cysteine proteases that include ubiquitously expressed μ- and m-calpains. Both are heterodimers consisting of a distinct large catalytic subunit (calpain 1 for μ-calpain and calpain 2 for m-calpain) and a common regulatory subunit (calpain 4). The physiological roles of calpain remain unclear in the organs, including the heart, but it has been suggested that calpain is activated by Ca(2+) overload in diseased hearts, resulting in cardiac dysfunction.

Inhibition of autophagy in the heart induces age-related cardiomyopathy.

Constitutive autophagy is important for control of the quality of proteins and organelles to maintain cell function. Damaged proteins and organelles accumulate in aged organs. We have previously reported that cardiac-specific Atg5 (autophagy-related gene 5)-deficient mice, in which the gene was floxed out early in embryogenesis, were born normally, and showed normal cardiac function and structure up to 10 weeks old.

Activation of MTK1/MEKK4 induces cardiomyocyte death and heart failure.

MTK1 (MEKK4) is a mitogen-activated protein kinase kinase kinase that regulates the activity of its downstream mitogen-activated kinases, p38, and c-Jun N-terminal kinase (JNK). However, the physiological function of MTK1 in the heart remains to be determined. Here, we attempted to elucidate the function of MTK1 in the heart using in vitro and in vivo models.

The I{kappa}B kinase {beta}/nuclear factor {kappa}B signaling pathway protects the heart from hemodynamic stress mediated by the regulation of manganese superoxide dismutase expression.

Cardiomyocyte death plays an important role in the pathogenesis of heart failure. The nuclear factor (NF)-kappaB signaling pathway regulates cell death, however, the effect of NF-kappaB pathway on cell death can vary in different cells or stimuli. The purpose of the present study was to clarify the in vivo role of the NF-kappaB pathway in response to pressure overload.

Atherosclerotic and thrombogenic neointima formed over sirolimus drug-eluting stent: an angioscopic study.

Objectives: We sought to examine by angioscopy the neointima formation and thrombogenic potential of the neointima after deployment of a drug-eluting stent (DES).

Background: Late stent thrombosis after DES implantation, a major safety concern, has been associated with poor strut coverage by neointima. Intracoronary angioscopy provides a method for visual evaluation of stent coverage by neointima and detection of thrombus in the stented coronary segment.

Plaque color analysis by the conventional yellow-color grading system and quantitative measurement using LCH color space.

Background: Yellow plaques of higher color grades are regarded as more vulnerable. We tried to elucidate the characteristics of yellow color that are regarded as the sign of vulnerable plaques by an objective and quantitative plaque color analysis.

Methods: The color of yellow plaques was quantitatively analyzed using LCH color space and was presented by the maximum values of lightness (Lmax), chroma (Cmax), and hue (Hmax).

Acute myocardial infarction without disrupted yellow plaque in young patients below 50 years old.

Objective: Thrombosis caused by disrupted yellow plaque is regarded as a cause of acute myocardial infarction (MI). However, it has not been clarified if young patients have the same pathophysiology as older ones. Therefore, we elucidated clinical and angioscopic characteristics of young patients.

Angioscopic evaluation of neointima coverage: sirolimus drug-eluting stent versus bare metal stent.

Background: The process of neointima formation after bare metal stent (BMS) implantation has been previously elucidated by angioscopic observations; however, that after drug-eluting stent (DES) implantation has not been clarified. Therefore, we compared the angioscopic appearance of neointima over DESs with that over BMSs 6 months after implantation.

Methods And Results: Patients who received an implantation of a BMS (n = 13) or a sirolimus DES (n = 24) were included in this study.

Number of yellow plaques detected in a coronary artery is associated with future risk of acute coronary syndrome: detection of vulnerable patients by angioscopy.

Objectives: We sought to test whether the risk of acute coronary syndrome (ACS) can be estimated by angioscopy.

Background: Disruption of vulnerable plaque and subsequent thrombosis is regarded as a major mechanism of ACS. Although yellow plaques are supposedly vulnerable, the association between angioscopically determined extent of coronary atherosclerosis and risk of ACS events has not been reported.

Angioscopically-determined extent of coronary atherosclerosis is associated with severity of acute coronary syndrome.

Objective: Some patients with acute coronary syndrome (ACS) have large myocardial infarction but others have small or no infarction. However, what makes this difference has not been clarified. We compared the angioscopic findings between those two categories of ACS patients and examined the association between the severity of ACS and the morphology of both culprit lesion and nonculprit coronary segments.