Upregulation of caveolin-1 expression is associated with structural modifications of endothelial cells in diabetic lung

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• 作者：Elena Uyy ; Felicia Antohe ; Luminita Ivan ; Raluca Haraba ; Dorel Lucian Radu ; Maya Simionescu
• 关键词：Caveolin-1 ; Caveolae ; Endothelial cell ; Type I diabetes mellitus ; Streptozotocin ; Transgenic Diabetic mice ; Caveolae-enriched membrane domains
• 刊名：Microvascular Research
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：79
• 期：2
• 页码：154-159
• 全文大小：550 K

文摘

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.