Institute of Cellular Biology and Pathology Nicolae Simionescu, 8, BP Hasdeu Street, PO Box 35-14, 050568 Bucharest, Romania.
Microvasc Res. 2010 Mar;79(2):154-9. doi: 10.1016/j.mvr.2009.11.008. Epub 2010 Jan 6.
Diabetes and the associated hyperglycemia affect pulmonary physiology and biochemistry inducing endothelial impairment, as the first step in lung vascular dysfunction. Caveolin-1, a characteristic protein of endothelial caveolae, acts as a scaffolding protein involved in signal transduction, cholesterol homeostasis, and vesicular trafficking. To document the effect of hyperglycemia on lung endothelial cells, we designed experiments on streptozotocin-induced diabetes and on double transgenic diabetic mice and investigated (1) the early morphological changes occurring in endothelial cells, (2) the ACE activity and cholesterol content of caveolae-rich membrane microdomains, and (3) the protein and gene expression of caveolin-1. We provide evidence that in diabetic lung, the endothelial cell displays an increased number of caveolae and enlarged surface area and a well-developed synthetic machinery, changes that correlate with an overall augmented ACE activity and cholesterol content and overexpression (gene and protein) of caveolin-1. Targeting the endothelial cell surface molecules modulated by hyperglycemia, such as caveolin-1 and ACE could be an additional therapeutic strategy in diabetes.
糖尿病及相关高血糖会影响肺生理和生化功能，导致内皮损伤，这是肺血管功能障碍的第一步。窖蛋白-1（caveolin-1）是内皮小窝的特征性蛋白，作为一种支架蛋白，参与信号转导、胆固醇稳态和囊泡运输。为了研究高血糖对肺内皮细胞的影响，我们设计了链脲佐菌素诱导的糖尿病实验和双转基因糖尿病小鼠实验，并研究了（1）内皮细胞中早期发生的形态变化，（2）富含 caveolae 的膜微区中的 ACE 活性和胆固醇含量，以及（3）caveolin-1 的蛋白和基因表达。我们的研究结果表明，在糖尿病肺中，内皮细胞 caveolae 的数量增加，表面积增大，合成机制发达，这些变化与 ACE 活性和胆固醇含量整体升高以及 caveolin-1 的过度表达（基因和蛋白）相关。针对高血糖调节的内皮细胞表面分子，如 caveolin-1 和 ACE，可能是糖尿病治疗的另一种策略。
