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en: Roles of the Androgen - Androgen Receptor System in Vascular Angiogenesis.

en: Journal of Atherosclerosis and Thrombosis


en: インスリン注射により生じた皮下硬血を有する患者の実態調査とその介入の有用性の検討

en: Practice

ja: プラクティス


en: Effects of Statins on Cardiorenal Syndrome.

en: Cardiovascular disease and renal disease have a close relationship that forms a vicious cycle as a cardiorenal syndrome (CRS). Oxidative stress, endothelial dysfunction, and vascular inflammation could be therapeutic targets when the renin-angiotensin-aldosterone system is activated by accumulation of conventional cardiovascular risk factors; however, a strategy for management of CRS has not been established yet. Statins, HMG-CoA reductase inhibitors, have not only cholesterol-lowering effects but also pleiotropic effects on cardiovascular systems, including anti-inflammatory and antioxidant effects and improvement of nitric oxide bioavailability. Since recent studies have indicated that statins have beneficial effects on chronic kidney disease and heart failure as well as coronary artery disease in cholesterol-lowering-dependent/independent manners, treatment with statins might be a successful strategy for preventing deterioration of CRS.

en: International Journal of Vascular Medicine


en: Effects of androgens on cardiovascular remodeling.

en: Androgens, the male sex hormones, exert various biological effects on many target organs through the transcriptional effects of the nuclear androgen receptor (AR). ARs are expressed not only in classical target organs, such as the brain, genital organs, bone, and skeletal muscles, but also in the cardiovascular system. Because the female sex hormones estrogens are well known to protect against cardiovascular disease, sex has been considered to have a significant clinical impact on cardiovascular mortality. However, the influence of androgens on the cardiovascular system has not been fully elucidated. To clarify this issue, we analyzed the effects of administration of angiotensin II and doxorubicin, an anticancer agent, in a loading model in male wild-type and AR-deficient mice. In this review, we focus on the actions of androgens as potential targets for the prevention of cardiovascular diseases in males.

en: The Journal of Endocrinology

ja: The Journal of Endocrinology


en: 【メタボリックシンドロームと多臓器障害】 メタボリックシンドロームを司るもの

ja: 【メタボリックシンドロームと多臓器障害】 メタボリックシンドロームを司るもの

en: 腹囲の増大を基盤として，脂質異常，血圧異常，糖代謝異常などの複合代謝異常状態を呈するメタボリックシンドロームは，その罹患該当者が近年増加の一途をたどっている．メタボリックシンドロームは，心血管イベントの発症リスクを増大させることから，その病態把握と治療介入の必要性が強く求められている．これまで多くの研究者が，基礎医学および臨床医学の面からメタボリックシンドロームの病態制御機構の探索に取り組んでいるが，本特集では，アディポネクチン，レニン・アンジオテンシン系，高血圧症，慢性腎臓病・骨格筋の役割などの5つの視点からその病態基盤や臓器合併症の解明にせまる事とした．これらの分野の最新の知見を吸収し，理解を深めることが，メタボリックシンドロームひいては心血管病の予防に向けた臨床的な実践につながると期待している．(著者抄録)

en: The Cell

ja: 細胞


en: 遺伝子改変動物から学ぶ血栓症(第28回) ヘパリンコファクターII欠損マウスにおける心血管リモデリング解析

en: Thrombosis and Circulation

ja: 血栓と循環


en: Transforming Growth Factor-1 as a Common Target Molecule for Development of Cardiovascular Diseases, Renal Insufficiency and Metabolic Syndrome.

en: Transforming growth factor-1 (TGF-1) is a polypeptide member of the transforming growth factor superfamily of cytokines. It is a secreted protein that performs many cellular functions including control of cell growth, cell proliferation, cell differentiation and apoptosis. In the cardiovascular system, TGF-1 plays pivotal roles in the pathogenesis of hypertension, restenosis after percutaneous coronary intervention, atherosclerosis, cardiac hypertrophy and heart failure. In addition, TGF-1 has been shown to be increased in adipose tissue of obese subjects with insulin resistance. Furthermore, TGF-1 is a potent initiator of proliferation of renal mesangial cells leading to chronic kidney disease. Some currently available agents can manipulate TGF-1 expression leading to amelioration of cardiovascular diseases. Thus, an understanding of interactions between chronic kidney disease and metabolic syndrome and the development of cardiovascular diseases is an important issue, and attention should be given to TGF-1 as a crucial factor for regulation and modulation of those pathological conditions.

en: Cardiology Research and Practice

ja: Cardiology Research and Practice


en: Heparin cofactor II attenuates vascular remodeling in humans and mice.

en: Heparin cofactor II (HCII), a serine protease inhibitor (serpin), inactivates thrombin action in the subendothelial layer of the vascular wall. Because a congenitally HCII-deficient patient has been shown to have multiple atherosclerotic lesions, it is hypothesized that HCII plays a pivotal role in the development of vascular remodeling, including atherosclerosis. To clarify this issue, 3 clinical studies concerning plasma HCII activity and atherosclerosis were carried out, and results demonstrated that a higher incidence of in-stent restenosis after percutaneous coronary intervention, maximum carotid arterial plaque thickness, and prevalence of peripheral arterial disease occurred in subjects with low plasma HCII activity. Furthermore, HCII-deficient mice were generated by a gene targeting method to determine the mechanism of the vascular protective action of HCII. Because HCII(-/-) mice were embryonically lethal, we used HCII(+/-) mice and found that they manifested augmentation of intimal hyperplasia and increased thrombosis after cuff or wire injury to the femoral arteries. HCII(+/-) mice with vascular injury showed augmentation of inflammatory cytokines and chemokines and oxidative stress. These abnormal phenotypes of vascular remodeling observed in HCII(+/-) mice were almost restored by human HCII protein supplementation. HCII protects against vascular remodeling, including atherosclerosis, in both humans and mice, and plasma HCII activity might be a predictive biomarker and novel therapeutic target for the prevention of cardiovascular diseases.

en: Circulation Journal

ja: Circulation Journal


en: 2009年度 井村臨床研究奨励賞受賞記念論文 新規動脈硬化抑制因子としてのヘパリンコファクター2の臨床的意義および分子生物学的解析

en: The Medical Frontline

ja: 最新医学


en: Heparin Cofactor II as a Novel Vascular Protective Factor Against Atherosclerosis.

en: Heparin cofactor II (HCII) specifically inhibits thrombin action at the site of vascular wall injury. We encountered a congenital HCII deficiency patient with advanced multiple atherosclerotic lesions. This patient led us to conduct clinical studies to examine the role of HCII against atherosclerosis. We found that the incidence of in-stent restenosis after percutaneous coronary intervention, severity of carotid atherosclerosis and prevalence of peripheral arterial disease are inversely associated with plasma HCII activity. In order to clarify the vascular protective action of HCII, we generated HCII- deficient mice by gene targeting. In contrast to a previous study, HCII(-/-) mice were embryonically lethal. In HCII(+/-) mice, accelerated intimal hyperplasia and frequent thrombosis were observed after cuff or wire injury of femoral arteries. The number of protease-activated receptor-1 (PAR-1) -positive cells and the gene expression levels of inflammatory cytokines and chemokines were increased in the thickened vascular walls of HCII(+/-) mice. The accelerated intimal hyperplasia in HCII+/- mice with vascular injury was attenuated by human HCII administration. Furthermore, HCII deficiency exaggerated aortic plaque formation with increased oxidative stress in apolipoprotein E(-/-) mice. These results demonstrate that HCII protects against thrombin-induced vascular remodeling in both humans and mice and suggest that HCII is a predictive biomarker and therapeutic target for atherosclerosis.

en: Journal of Atherosclerosis and Thrombosis


en: Clinical significance of lipid disorders and atherosclerosis in metabolic syndrome

ja: 高脂血症・動脈硬化とメタボリックシンドローム (特集 メタボリックシンドロームの克服に向けて)

en: The cardiovascular disease has been increasingly recognized over the last decade. The metabolic syndrome is associated with increased risk for development of dyslipidemia leading to atherosclerosis. In addition to healthy lifestyle promotion, treatment of atherogenic dyslipidemia using lipid lowering agents such as fibrates and statins is useful. In fact, bezafibrate reduces the incidence of myocardial infarction in patients with metabolic syndrome during long-term follow-up. Early detection of atherosclerosis including endothelial dysfunction is very important strategy for preventing cardiovascular events in patients with metabolic syndrome. We attempt to establish multiphasic health testing system(Anti-Aging Medical Center : AAMC)using recently-developed devices for medical diagnosis in Tokushima University Hospital.

en: Shikoku Acta Medica

ja: 四国医学雑誌


en: Vitamin D-vitamin D receptor system regulates antithrombogenicity in vivo.

en: Although it has been well documented that vitamin D receptor (VDR) activation influences the expression of various genes involved in calcium homeostasis and cell differentiation, the physiological role of VDR action in hemostasis remains unclear. We studied thrombogenicity in normocalcemic VDR knock-out (KO) mice on a high calcium diet in comparison with that in wild-type mice and that in hypocalcemic VDRKO mice fed a regular diet. Platelet aggregation was significantly enhanced in normocalcemic VDRKO mice. Aortic endothelial nitric-oxide (NO) synthase expression and urinary NOx excretion were reduced in hypocalcemic VDRKO mice but not in normocalcemic VDRKO mice. The gene expression of antithrombin in the liver and that of thrombomodulin in the aorta, liver and kidney were down-regulated in hypo- and normocalcemic VDRKO mice, whereas tissue factor gene expression in the liver and kidney was up-regulated in VDRKO mice regardless of plasma calcium level. Furthermore, VDRKO mice manifested an exacerbated multi-organ thrombus formation after exogenous lipopolysaccharide injection regardless of the calcemic conditions. These results demonstrate that the vitamin D-VDR system plays a pivotal role in antithrombogenicity in vivo.

en: Clinical Calcium

ja: Clinical Calcium


en: Nuclear vitamin D receptor regulates antithrombogenicity in vivo

ja: ビタミンD受容体を介した生体内血液凝固制御機構の解析

en: Japanese Journal of Thrombosis and Hemostasis

ja: 日本血栓止血学会誌


en: 【慢性心不全の分子機構 新しい治療戦略を求めて】 性ステロイドと心保護作用

ja: 【慢性心不全の分子機構 新しい治療戦略を求めて】 性ステロイドと心保護作用

en: Cardioangiology

ja: 循環器科


en: 2型糖尿病の発症およびその心腎血管障害の予測マーカーとしてのヘパリンコファクターIIの臨床的意義

en: 三井厚生記念財団第20回医学研究特別助成報告書

ja: 三井厚生記念財団第20回医学研究特別助成報告書

misc_type: others


en: ヘパリンコファクターIIの抗動脈硬化作用

ja: ヘパリンコファクターIIの抗動脈硬化作用

en: 著者等はこれまでに，血漿中のヘパリンコファクターII(HC II)活性が高い患者では冠動脈形成術後のステント再狭窄や頸動脈プラークの形成が抑制されることを報告してきたが，その分子機序は不明であった．そこで今回，HC II欠損マウスの血管傷害モデルを用いてHC IIが抗動脈硬化作用を示す機序について解析した．その結果，傷害血管に対する抗トロンビン作用が主要メカニズムであると考えられた．

en: 上原記念生命科学財団研究報告集

ja: 上原記念生命科学財団研究報告集