Role of Angiotension and CD36 Expression in Multiple Risk Factors for Atherosclerosis

血管紧张素和 CD36 表达在动脉粥样硬化多种危险因素中的作用

• 批准号: 17590705
• 负责人: NAKAMURA Tetsuya
• 金额: $ 2.11万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590705/
• 关键词: Hypertension; Insulin resistance; Angiotensin converting enzyme; atherosclerosis; ゲノム; 遺伝子; 循環器・高血圧; 老化

OBJECTIVE : Diiihydropyridine calcium channel blockers (CCB) can prevent the CV events in diabetes. Angiotensin II plays a key role in pathobiological events that lead to vascular disease. The present study examined the long-term effects of CCB and angiotensin II receptor blocker on the cardiovascular protective effects in hypertension.METHODS and RESULTS : Thirty-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rates, a model of diabetes with elevated BP, and normal control (Long Evans Tokushima Otsuka : LETO) rats were fed standard chow or chow containing CCB azelnidipine, 0.4 mg/g food (n=15 in each group) for 2 weeks. Angiotensin enzyme (ACE) mRNA in both renal cortex and medulla of OLETF was reduced compared to LETO rats, and further suppressed by azelnidipine. The renal cortical mineralocorticoid receptor (MCR) mRNA in OLETF was higher than in LETO, and reduced significantly by azelnidipine. MCR mRNA in the renal medulla did not differ significantly between 2 strains, and was unaltered by azelnidipine in either strain.In 46 patients with hypertension, the pulse wave velocity between the brachium and ankle (baPWV) was measured before and 24 weeks after the treatment with valsartan 40 to 160 mg/day. Systolic and diastolic blood pressures were decreased from 155±3 to 140±3 and from 90±2 to 82±2 mmHg, respectively. The baPWV also decreased from 1853±49 cm/sec to 1682 ±52 cm/sec.CONCLUSION : We demonstrated that azelnidipine normalized the enhanced renal cortical expression of MCR mRNA and reduced renal ACE mRNA in diabetic rats. This is the first report providing that L-type CCB can down-regulated renal expression of ACE and MCR mRNA. We conclude that the treatment effect of valsartan reduces arterial stiffness regardless of baseline blood pressure. Blood pressure reduction alone does not appear to account entirely for the benefits of valsartan therapy on arterial stiffness.

目的：二氢吡啶钙通道阻滞剂（CCB）可预防糖尿病的心血管事件。血管紧张素II在导致血管疾病的病理生物学事件中起关键作用。本研究考察了CCB和血管紧张素受体阻滞剂对高血压患者心血管保护作用的长期影响。方法与结果：将30周龄雄性大鼠（Long Evans Tokushima Fatty， OLETF）和正常对照（Long Evans Tokushima Otsuka: LETO）分别饲喂标准饲料和含CCB azelnidipine， 0.4 mg/g食物的饲料（每组15只）2周。与LETO大鼠相比，OLETF大鼠肾皮质和肾髓质的血管紧张素酶（ACE） mRNA均降低，并进一步被阿泽尼地平抑制。OLETF组肾皮质矿化皮质激素受体（MCR） mRNA水平高于LETO组，阿泽尼地平组显著降低MCR mRNA水平。两株大鼠肾髓质MCR mRNA无显著差异，阿泽尼地平对两株大鼠肾髓质MCR mRNA无显著影响。对46例高血压患者采用缬沙坦40 ~ 160 mg/天治疗前和治疗后24周测定肱与踝关节间脉波速度（baPWV）。收缩压和舒张压分别从155±3 mmHg降至140±3 mmHg和从90±2 mmHg降至82±2 mmHg。baPWV也从1853±49 cm/sec下降到1682±52 cm/sec。结论：阿泽尼地平可使糖尿病大鼠肾皮质MCR mRNA表达增强和肾ACE mRNA表达降低。这是首次报道l型CCB可以下调肾脏ACE和MCR mRNA的表达。我们得出结论，缬沙坦的治疗效果降低动脉僵硬，而不考虑基线血压。缬沙坦治疗对动脉僵硬的益处似乎不能完全由血压降低来解释。

项目成果

Selective Angiotensin Receptor Antagonism with Valsartan Decreases Arterial Stiffness Independently of Blood Pressure Lowering in Hypertensive Patients

• DOI: 10.1291/hypres.28.937
• 发表时间: 2005-12
• 期刊: Hypertension Research
• 影响因子: 5.4
• 作者: Tetsuya Nakamura;S. Fujii;J. Hoshino;Y. Saito;H. Mizuno;Yuichiro Saito;M. Kurabayashi

Effect of transdermal hormone replacement therapy on the monocyte chemoattractant protein-1 concentrations and other vascular inflammatory markers and on endothelial function in postmenopausal women.

透皮激素替代疗法对绝经后妇女单核细胞趋化蛋白-1 浓度和其他血管炎症标志物以及内皮功能的影响。

• 发表时间: 2005
• 期刊: American Journal of Cardiology 96
• 作者: Watanabe T;et al.;Tateno K;Sumino H.
• 通讯作者: Sumino H.

Simvastatin induces heat shock factor 1 in vascular endothelial cells

• DOI: 10.1016/j.atherosclerosis.2005.10.045
• 发表时间: 2006-10-01
• 期刊: ATHEROSCLEROSIS
• 影响因子: 5.3
• 作者: Uchiyama, Tsuyoshi;Atsuta, Hiroyuki;Kurarbayashi, Masahiko
• 通讯作者: Kurarbayashi, Masahiko

Comparison of Oral and Transdermal Hormone Replacement Therapy on Arterial Stiffness and Vascular Inflammatory Markers in Postmenopausal Women.

口服和透皮激素替代疗法对绝经后妇女动脉僵硬和血管炎症标志物的比较。

• 发表时间: 2005
• 期刊: Circulation Journal 69(Suppl 1)
• 作者: Nishimura S;Nagai S;Sata M;Katoh M;Yamashita H;et al.;Sato T.;Sumino H.
• 通讯作者: Sumino H.

Transdermal Hormone Replacement Therapy Reduces Carotid Artery Wall Thickness and Levels of Vascular Inflammatory Markers in Postmenopausal Women.

透皮激素替代疗法可减少绝经后妇女的颈动脉壁厚度和血管炎症标志物水平。

• 发表时间: 2005
• 期刊: Circulation Journal 69(Suppl 1)
• 作者: Fukuhara;S.;Suzuki;H.;Masaoka;T.;Arakawa;M.;Hosoda;H.;Minegishi;Y.;Kangawa;K.;Ishii;H.;Kitajima;M.;Hibi;T.;Fujita H.;Sumino H.
• 通讯作者: Sumino H.