Gene therapy for pulmonary hypertension

(1)心肌细胞和血管平滑肌细胞中存在诱导型一氧化氮合酶(INOS)。我们发现神经体液因子调节这些细胞中iNOS的表达。例如，蛋白激酶C激活剂，如血管紧张素II和加压素，可增强细胞因子诱导的心肌细胞iNOS的表达。CAMP产生的神经体液因子肾上腺髓质素和异丙肾上腺素也能促进细胞因子刺激的心肌细胞产生NO。(2)我们研究了腺相关病毒载体能否有效地转导心肌细胞和血管平滑肌细胞，并发现它们可以有效地转移到这些细胞中。这些观察结果表明，AAV载体在心脏基因治疗中很有前途。

(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.