Gene transfer of endothelial nitric oxide synthase alters endothelium-dependent relaxations in aortas from diabetic rabbits.
Gene transfer of endothelial nitric oxide synthase alters endothelium-dependent relaxations in aortas from diabetic rabbits.
复制标题
内皮一氧化氮合酶的基因转移改变糖尿病兔主动脉内皮依赖性松弛。
DOI：
10.1007/s001250050052
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发表时间：
2000
期刊：
影响因子：
8.2
通讯作者：
O'Brien,T
中科院分区：
文献类型：
--
作者：
Zanetti,M;Sato,J;Katusic,ZS;O'Brien,T
目标/假设。心血管疾病是糖尿病的主要死亡原因。在人类和糖尿病动物模型中都观察到了内皮依赖性的异常松弛，一氧化氮(NO)的生物利用度降低被认为与这一缺陷有关。因此，本研究的目的是检测腺病毒介导的内皮型一氧化氮合酶(ENOS)基因转移是否改变糖尿病血管的血管反应性。对9只四氧嘧啶糖尿病兔(血糖2 6.5±1.2 mmol/L；HbA1c，6.4±0.3%)和9只对照兔(血糖11.1±1.3 mmol/L，HbA1c，2.1±0.1%)的胸主动脉和颈动脉血管反应性进行了研究。体外转导复制缺陷型腺病毒编码基因preNOS(AdeNOS)或β-半乳糖苷酶(AdβGal)后，检测糖尿病大鼠胸主动脉血管反应性。高血糖10周后，糖尿病兔主动脉对乙酰胆碱的内皮依赖性舒张功能受损，但颈动脉血管内皮依赖性舒张功能正常。相反，两条血管对钙离子载体和一氧化氮供体的反应是正常的。β-半乳糖苷酶组织化学染色和前β免疫组织化学染色显示转基因表达分别位于血管内皮细胞和外膜。在苯肾上腺素的次最大收缩中，ADENOS转导的糖尿病血管对低浓度乙酰胆碱(3×10-8~10-7mol/L)的松弛作用增强。这些发现表明，腺病毒介导的NOS基因转移到糖尿病大动脉改变了血管的反应性。[Diabetologia(2000)43：340-347]
Aims/hypothesis. Cardiovascular disease is the leading cause of death in diabetes mellitus. Abnormal endothelium-dependent relaxation is observed both in humans and in animal models of diabetes mellitus and decreased bioavailability of nitric oxide (NO) is thought to be involved in this defect. Therefore, the aim of this study was to test whether adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) alters vascular reactivity of diabetic vessels.¶Methods. Vascular reactivity was first assessed in thoracic aortas and carotid arteries from nine alloxan-induced diabetic (plasma glucose, 26.5 ± 1.2 mmol/l; HbA1 c, 6.4 ± 0.3 %) and nine control rabbits (plasma glucose, 11.1 ± 1.3 mmol/l; HbA1 c, 2.1 ± 0.1 %). Vascular reactivity was next examined in thoracic aortas of diabetic animals after ex vivo transduction with replication-deficient adenovirus encoding gene foreNOS(AdeNOS) orβ-galactosidase (Adβgal).¶Results. After 10 weeks of hyperglycaemia, endothelium-dependent relaxation to acetylcholine was impaired in diabetic aorta, but was normal in carotid arteries from diabetic rabbits. In contrast, responses of both vessels to calcium ionophore and nitric oxide donor were normal. Histochemical staining forβ-galactosidase and immunohistochemistry foreNOS showed transgene expression in the endothelium and adventitia in Adβgaland AdeNOStransduced vessels, respectively. During submaximum contractions with phenylephrine, relaxations to low concentrations of acetylcholine (3 × 10–8to 10–7mol/l) were augmented in AdeNOStransduced diabetic vessels.¶Conclusion/interpretation. These findings suggest that adenovirus-mediated gene transfer ofeNOSto diabetic aorta alters vascular reactivity. [Diabetologia (2000) 43: 340–347]