Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 72, Issue SupplementA
Displaying 1-8 of 8 articles from this issue
Special Contribution
  • Role of Cardiac Remodeling
    Arunima Misra, Douglas L. Mann
    2008 Volume 72 Issue SupplementA Pages A1-A7
    Published: 2008
    Released on J-STAGE: September 25, 2008
    Advance online publication: September 05, 2008
    JOURNAL FREE ACCESS
    Heart failure (HF) is clinical syndrome that develops and progresses as a result of the overexpression of biologically active molecules that are sufficient to cause deleterious effects on the heart and circulation. Over the past 2 decades the adherence to practice guidelines for treating HF, including the use of angiotensin-converting enzyme inhibitors/angiotensin-receptor antagonists and β-blockers, has resulted in improved survival for patients. However, despite the use of these evidence-based strategies that block the deleterious effects of neurohormonal activation, the overall mortality for HF remains unacceptably high. Unfortunately, when patients remain symptomatic despite having their medical and/or device therapies optimized, the "next steps" to improving patient morbidity are not at all clear. Thus, there remains an unmet need with respect to the treatment of HF patients. The concept that cardiac remodeling represents an important mechanism for disease progression in HF is reviewed, as well as discussion of several novel treatment strategies with respect to devices that are intended to prevent worsening cardiac remodeling. (Circ J 2008; Suppl A: A-1 - A-7)
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  • Javier Díez
    2008 Volume 72 Issue SupplementA Pages A8-A12
    Published: 2008
    Released on J-STAGE: September 25, 2008
    Advance online publication: September 04, 2008
    JOURNAL FREE ACCESS
    Although hypertensive heart disease (HHD) is clinically characterized by development of left ventricular hypertrophy in the absence of a cause other than arterial hypertension, changes in the composition of myocardial tissue also develop in arterial hypertension, leading to structural remodeling of the myocardium (eg, fibrosis). Myocardial fibrosis is the major determinant of diastolic dysfunction/failure in patients with HHD. Recent available data on the determination of serum concentrations of collagen-derived serum peptides, as well as quantitative analysis of echoreflectivity to address the presence of fibrosis in the myocardium of hypertensive patients, are promising. In addition, preliminary data suggest that the goal of reducing myocardial fibrosis is achievable using specific pharmacological agents in patients with HHD. (Circ J 2008; Suppl A: A-8 - A-12)
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Invited Review
Molecular Mechanisms
  • Toru Oka, Issei Komuro
    2008 Volume 72 Issue SupplementA Pages A13-A16
    Published: 2008
    Released on J-STAGE: September 25, 2008
    Advance online publication: September 05, 2008
    JOURNAL FREE ACCESS
    Heart failure is a condition in which the heart cannot supply enough blood to the body's organs, and is a final common consequence of various heart diseases. In the past 2 decades, much progress has been made in understanding the molecular and cellular processes that contribute to cardiac hypertrophy and heart failure, leading to the development of effective therapies. However, heart failure remains a leading cause of mortality worldwide and the precise molecular mechanisms that mediate the transition of cardiac hypertrophy to heart failure are largely undefined. This review discusses the potential mechanisms of heart failure progression focusing on (1) cardiac myocyte loss, (2) abnormalities of calcium handling, and (3) myocardial ischemia and hypoxia. These factors are closely related, and are considered to contribute to the pathogenesis of contractile dysfunction and heart failure in a cooperative manner. Elucidation of the molecular mechanisms underlying the transition of cardiac hypertrophy to heart failure will lead to the development of novel therapeutic strategies for heart diseases. (Circ J 2008; Suppl A: A-13 -A-16)
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  • Kazuhiko Nishida, Kinya Otsu
    2008 Volume 72 Issue SupplementA Pages A17-A21
    Published: 2008
    Released on J-STAGE: September 25, 2008
    Advance online publication: September 05, 2008
    JOURNAL FREE ACCESS
    Heart failure (HF) has become the dominant cardiovascular disorder in the Western world and Japan, so there is an urgent need to clarify the mechanisms governing pathological remodeling mediated through cell death, and to identify ways of preventing and treating HF. Historically, there are 3 types of cell death: apoptosis, autophagy and necrosis. Apoptosis, a form of programmed cell death, has been well characterized and the molecular events involved in apoptotic death are well understood. Necrosis is often defined in a negative manner: death lacking the characteristics of programmed cell death and thus accidental and uncontrolled. However, recent studies indicate that necrosis is tightly regulated. Autophagy is a cell survival mechanism that involves degradation and recycling of cytoplasmic components. In contrast to the other 2 mechanisms, autophagy may mediate cell death under specific circumstances. In fact, damaged cardiomyocytes that show characteristics of autophagy have been observed during HF. However, a recent study indicated that upregulation of autophagy in the failing heart is an adaptive response. This review summarizes recent findings regarding the molecular mechanisms of cardiomyocyte cell death in HF. (Circ J 2008; Suppl A: A-17 - A-21)
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  • Masafumi Yano, Takeshi Yamamoto, Shigeki Kobayashi, Yasuhiro Ikeda, Ma ...
    2008 Volume 72 Issue SupplementA Pages A22-A30
    Published: 2008
    Released on J-STAGE: September 25, 2008
    Advance online publication: September 04, 2008
    JOURNAL FREE ACCESS
    Structural and functional alterations in the Ca2+ regulatory proteins present in the sarcoplasmic reticulum (SR) have recently been shown to play a crucial role in the pathogenesis of heart failure (HF), and lethal arrhythmia as well. Chronic activation of the sympathetic nervous system induces abnormalities in both the function and structure of these proteins. For instance, the diastolic Ca2+ leak through the SR Ca2+ release channel (ryanodine receptor) reduces the SR Ca2+ content, inducing contractile dysfunction. Moreover, the Ca2+ leak provides a substrate for delayed afterdepolarization that leads to lethal arrhythmia. There is a considerable body of evidence regarding the role of Ca2+ cycling abnormality in HF. (Circ J 2008; Suppl A: A-22 - A-30)
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  • Hiroyuki Tsutsui, Shintaro Kinugawa, Shouji Matsushima
    2008 Volume 72 Issue SupplementA Pages A31-A37
    Published: 2008
    Released on J-STAGE: September 25, 2008
    Advance online publication: September 04, 2008
    JOURNAL FREE ACCESS
    Recent experimental and clinical studies have suggested that oxidative stress is enhanced in heart failure. The production of oxygen radicals is increased in the failing heart while antioxidant enzyme activities are preserved. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and also a target against oxidant-induced damage in the failing myocardium. Chronic increases in oxygen radical production in the mitochondria can lead to a catastrophic cycle of mitochondrial DNA (mtDNA) damage, as well as functional decline, further oxygen radical generation, and cellular injury. Reactive oxygen species induce myocyte hypertrophy, apoptosis, and interstitial fibrosis by activating matrix metalloproteinases. These cellular events play an important role in the development and progression of maladaptive cardiac remodeling and failure. Therefore, oxidative stress and mtDNA damage are good therapeutic targets. Overexpression of peroxiredoxin-3 (Prx-3), mitochondrial antioxidant, or mitochondrial transcription factor A (TFAM) could ameliorate the decline in mtDNA copy number in failing hearts. Consistent with alterations in mtDNA, the decrease in oxidative capacities is also prevented. Therefore, the activation of Prx-3 or TFAM expression could ameliorate the pathophysiological processes seen in myocardial failure. Inhibition of oxidative stress and mtDNA damage could be novel and potentially effective treatment strategies for heart failure. (Circ J 2008; Suppl A: A-31 - A-37)
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  • Akinori Kimura
    2008 Volume 72 Issue SupplementA Pages A38-A48
    Published: 2008
    Released on J-STAGE: September 25, 2008
    Advance online publication: September 04, 2008
    JOURNAL FREE ACCESS
    Cardiomyopathy is defined as a cardiac disease caused by functional abnormality of cardiac muscle, and the etiology of the functional abnormality includes both extrinsic and intrinsic factors. Cardiomyopathy caused by the intrinsic factors is defined as idiopathic or primary cardiomyopathy, and there are several clinical phenotypes, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The major intrinsic factor is gene mutations, and linkage studies, as well as candidate gene approaches, have deciphered multiple disease genes for hereditary primary cardiomyopathy. Of note is that mutations in the same disease gene can be found in different clinical phenotypes of cardiomyopathy. Functional analyses of disease-related mutations have revealed that characteristic functional alterations are associated with the clinical phenotypes, such that increased and decreased Ca2+ sensitivity because of sarcomere mutations are associated with HCM and DCM, respectively. In addition, recent data have suggested that mutations in the Z-disc components found in HCM and DCM may result in increased and decreased stiffness of the sarcomere (ie, stiff sarcomere and loose sarcomere, respectively). More recently, mutations in the components of the I region can be found in hereditary cardiomyopathy, further complicating the etiology of primary cardiomyopathy. (Circ J 2008; Suppl A: A-38 - A-48)
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Treatment
  • Shinsuke Yuasa, Keiichi Fukuda
    2008 Volume 72 Issue SupplementA Pages A49-A55
    Published: 2008
    Released on J-STAGE: September 25, 2008
    Advance online publication: September 05, 2008
    JOURNAL FREE ACCESS
    Severe heart failure is associated with damage to the myocardium that is irreversible with current medical therapies. Recent experimental and clinical studies, however, have opened the possibility of solving many of the associated problems, making this an exciting and tangible goal. There are many potential cell sources for regenerative cardiac medicine, including bone marrow stem cells, endothelial progenitor cells, skeletal myocytes, adult cardiac stem cells, and embryonic stem (ES) cells. Although ES cells are highly proliferative and suitable for mass production, they are not autologous, and an efficient protocol is yet to be established to ensure selective cardiomyocyte induction. Recent studies have successfully established inducible pluripotent stem (iPS) cells from mouse and human fibroblasts by the gene transfer of 4 transcription factors that are strongly expressed in ES cells: Oct3/4, Sox2, Klf4 and c-Myc. iPS cells can differentiate into all 3 germ layer-derived cells and are syngeneic, indicating that they can become an ideal cell source for regenerative medicine. Despite these successes, the accumulating evidence from fields as diverse as developmental biology, stem cell biology and tissue engineering must be integrated to achieve the full potential of cardiac regenerative medicine. (Circ J 2008; Suppl A: A-49 - A-55)
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