Gene therapy for pulmonary hypertension

肺动脉高压的基因治疗

• 批准号: 08670821
• 负责人: IKEDA Uichi
• 金额: $ 1.6万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670821/
• 关键词: gene therapy; nitric oxide; hypertension; 心肥大; 遺伝子導入

(1).The inducible NO synthase (iNOS) exists in cardiac myocytes and vascular smooth muscle cells. We revealed that neurohumoral factors modulate iNOS expression in these cells. For example, protein kinase C activating agents such as angiotensin II and vasopressin augment cytokine-induced iNOS expression in cardiac myocytes. cAMP-generating neurohumoral factors adrenomedullin and isoproterenol also augment NO production by cytokine-stimulated cardiac myocytes.(2).We investigated whether cardiac myocytes and vascular smooth muscle cells could be efficiently transduced with adeno-associated virus (AAV) vectors, and found their efficient transfer into these cells. These observations suggest that AAV vectors are promising for cardiac gene therapy.

（1）诱导型一氧化氮合酶（inducible NO synthase，iNOS）存在于心肌细胞和血管平滑肌细胞中。我们发现，神经体液因子调节这些细胞中的iNOS表达。例如，蛋白激酶C激活剂如血管紧张素II和加压素增加了精氨酸诱导的心肌细胞中的iNOS表达。cAMP产生的神经体液因子肾上腺髓质素和异丙肾上腺素也增加了NO的生产由苦参碱刺激的心肌细胞。（2）我们研究了腺相关病毒（adeno-associated virus，AAV）载体能否有效地转导心肌细胞和血管平滑肌细胞，并发现它们能有效地转移到这些细胞中。这些观察结果表明，AAV载体是有希望的心脏基因治疗。

项目成果

Ikeda,U.: "Cyclic AMP augments cytokine-stimulatednitric oxide synthesis in rat cardiac myocytes." J.Mol.Cell.Cardiol.28. 789-795 (1996)

Ikeda,U.：“环磷酸腺苷增强大鼠心肌细胞中细胞因子刺激的一氧化氮合成。”

Shimpo,M.,Ikeda,U.: "Serotonin inhibits nitric oxide synthesis in rat vascular smooth muscle cells stimulated with interleukin-1." Eur.J.Pharmacol.338. 97-104 (1997)

Shimpo,M.，Ikeda,U.：“血清素抑制白细胞介素 1 刺激的大鼠血管平滑肌细胞中一氧化氮的合成。”

Ikeda,U.: "Adrenomedullin augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes." Circulation. 94. 2560-2565 (1996)

Ikeda，U.：“肾上腺髓质素增强细胞因子刺激的心肌细胞中诱导型一氧化氮合酶的表达。”

Ikeda, U.: "Endothelin-1inhibits nitric oxide synthesis in vscular smoothmuscle cells." Hypertension. 24. 65-69 (1997)

Ikeda, U.：“Endothelin-1 抑制血管平滑肌细胞中的一氧化氮合成。”

Ikeda,U.: "Adenosine stimulates nitric oxide synthesis in rat cardiac myocytes." Am.J.Physiol.273. H59-H65 (1997)

Ikeda,U.：“腺苷刺激大鼠心肌细胞中一氧化氮的合成。”