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en: Roles of histone acetylation sites in cardiac hypertrophy and heart failure.

en: Heart failure results from various physiological and pathological stimuli that lead to cardiac hypertrophy. This pathological process is common in several cardiovascular diseases and ultimately leads to heart failure. The development of cardiac hypertrophy and heart failure involves reprogramming of gene expression, a process that is highly dependent on epigenetic regulation. Histone acetylation is dynamically regulated by cardiac stress. Histone acetyltransferases play an important role in epigenetic remodeling in cardiac hypertrophy and heart failure. The regulation of histone acetyltransferases serves as a bridge between signal transduction and downstream gene reprogramming. Investigating the changes in histone acetyltransferases and histone modification sites in cardiac hypertrophy and heart failure will provide new therapeutic strategies to treat these diseases. This review summarizes the association of histone acetylation sites and histone acetylases with cardiac hypertrophy and heart failure, with emphasis on histone acetylation sites.

en: Frontiers in Cardiovascular Medicine

ja: Frontiers in Cardiovascular Medicine


en: Pharmacological approach for drug repositioning against cardiorenal diseases.

en: New applications of approved clinically used drugs are being discovered. Drug repositioning is a proposed strategy for developing these drugs as therapeutic agents for different diseases. Currently, approximately 2000 drugs are used in Japan. However, the compound targets and pathways involved in the pharmacological actions of 70-80% of these drugs have not been adequately clarified. Pharmacological examination of approved drugs is an important task in drug repositioning and vital for improving drug development efficiency. This review reports that angiotensin II type 1 receptor blockers show receptor-independent effects against reactive oxygen species generation in renal cells. Additionally, nitrosonifedipine has an antioxidative effect and protects endothelial cells against oxidative stress, and pioglitazone has multiple effects that improve dysfunctions in vascular control regulated by adrenergic and calcitonin gene-related peptide-containing nerves in animal models of diabetes. These data suggest that some approved drugs could be useful for treating cardiorenal diseases. Since cardiorenal diseases are likely to have chronic pathological conditions and require chronic drug administration, highly safe drugs are needed. Compared to newly developed drugs, drug repositioning of approved drugs with safety information is considered a particularly useful technique for searching new treatments for cardiorenal diseases. J. Med. Invest. 64: 197-201, August, 2017.

en: The Journal of Medical Investigation : JMI


en: 血管リモデリング形成における低酸素誘導因子の機能解析

ja: 血管リモデリング形成における低酸素誘導因子の機能解析

en: Japanese Journal of Circulation Research

ja: 血管


en: Drug repositioning research to improve the survival rate after cardiopulmonary arrest - utilizing large scale Medical Claims Database -

en: Approximately 100000 people suffer cardiopulmonary arrest in Japan every year, and the aging of society means that this number is expected to increase. Worldwide, approximately 100 million develop cardiac arrest annually, making it an international issue. Although survival has improved thanks to advances in cardiopulmonary resuscitation, there is a high rate of postresuscitation encephalopathy after the return of spontaneous circulation, and the proportion of patients who can return to normal life is extremely low. Treatment for postresuscitation encephalopathy is long term, and if sequelae persist then nursing care is required, causing immeasurable economic burdens as a result of ballooning medical costs. As at present there is no drug treatment to improve postresuscitation encephalopathy as a complication of cardiopulmonary arrest, the development of novel drug treatments is desirable. In recent years, new efficacy for existing drugs used in the clinical setting has been discovered, and drug repositioning has been proposed as a strategy for developing those drugs as therapeutic agents for different diseases. This review describes a large-scale database study carried out following a discovery strategy for drug repositioning with the objective of improving survival rates after cardiopulmonary arrest and discusses future repositioning prospects.

en: Journal of the Pharmaceutical Society of Japan

ja: 薬学雑誌


en: 間葉内皮転換が心臓の血管新生に関与する

ja: 間葉内皮転換が心臓の血管新生に関与する

en: Farumashia

ja: ファルマシア


en: Drug development for cardiorenal disease based on oxidative stress control

ja: 酸化ストレス制御を基盤とする新規心腎血管障害治療薬の開発

en: Oxidative stress is a key factor involved in the pathogenesis and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). Reactive oxygen species (ROS), produced as a result of redox reactions in various cells, have been recognized as key chemical mediators causing cellular damage and organ dysfunction in CVD and CKD. Nifedipine, a well-known calcium channel blocker, is extremely sensitive to light which gets converted to its nitroso analog, nitrosonifedipine (NO-NIF) in the presence of ultraviolet and visible light. The so formed NO-NIF blocks calcium channel quite weakly compared to that of nifedipine. However, we elucidated for the first time that NO-NIF is converted to NO-NIF radical which acquires extremely strong antioxidant property via reaction with unsaturated fatty acid or endothelial cells. We have already reported that NO-NIF reduces the cytotoxicity of cumene hydroperoxide, which hampers the integrity of cell membrane through oxidative stress, in endothelial cells. Additionally, we demonstrated that NO-NIF restored acetylcholine-responsive vascular relaxation and suppressed intercellular adhesion molecule-1 expression in the aorta of N(ω)-nitro-L-arginine methyl ester-treated rats, a model of vascular endothelial dysfunction. Recently, we reported that NO-NIF ameliorates angiotensin II-induced vascular remodeling via antioxidative effects in vivo and in vitro. These observations point towards the plausible, unique role of NO-NIF as a novel antioxidant which improves vascular dysfunction for overcoming CVD and CKD and the same has been highlighted in this review.


en: Role of Hypoxia-Inducible Factor1a (HIF-1a) in T cells in development of vascular remodeling

ja: 生体の低酸素応答と病態 -血管リモデリングにおける転写因子HIFの関与-

en: Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor1(HIF‐1). Impairment of HIF‐1‐ dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif‐1α specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. This minireview shows that HIF‐1α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell-mediated immune response and suggests potential new therapeutic strategies that target HIF‐1α.

en: Shikoku Acta Medica

ja: 四国医学雑誌