Human glomerular endothelium: interplay among glucose, free fatty acids, angiotensin II, and oxidative stress
Human glomerular endothelium: interplay among glucose, free fatty acids, angiotensin II, and oxidative stress
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DOI：
10.1152/ajprenal.00248.2009
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Raij, Leopoldo
中科院分区：
文献类型：
--
作者：
Jaimes, Edgar A.;Hua, Ping;Raij, Leopoldo
杨志华，杨文.人类肾小球内皮：葡萄糖、游离脂肪酸、血管紧张素II和氧化应激之间的相互作用。美国肾脏生理学杂志298：F125-F132，2010年。首次发表于2009年10月28日; doi：10.1152/ajprenal.00248.2009。肾小球内皮细胞（GEC）位于毛细血管袢内，邻近肾小球系膜。GEC作为调节肾小球微循环的代谢、生化和血液动力学信号的靶点。毫无疑问，高血糖、高血压和局部肾素-血管紧张素系统参与了糖尿病肾病（DN）的发生和发展。游离脂肪酸（FFA）和活性氧（ROS）是否与糖尿病大血管病变的内皮功能障碍有关，也有助于DN尚不清楚。由于来自不同器官和不同物种的内皮细胞可能显示不同的表型，我们使用人GEC来研究高糖对内皮细胞的影响。（22.5 mmol/l），FFA（800 μ mol/l）和血管紧张素II（ANG II; 10（-7）mol/l）对ROS的产生及其对内皮型一氧化氮合酶（eNOS）、环氧合酶-2（考克斯-2）、以及洋地黄素（PGs）的合成。我们证明了高糖而不是高FFA增加了功能失调的eNOS的表达，以及来自NADPH氧化酶（100%）和可能来自解偶联eNOS的ROS增加。ANG Ⅱ也能诱导NADPH氧化酶产生活性氧。高糖和ANG II通过ROS上调（100%）考克斯-2，并使前列环素（PGI（2））的合成显著增加300%。相反，FFA不上调考克斯-2，但增加PGI（2）（500%）。这些新的研究是首次在人类GEC中表征FFA、高血糖症和ANG II对ROS、考克斯-2和PG发生的不同作用及其在高血糖症早期阶段的相互作用。
Jaimes EA, Hua P, Tian R-X, Raij L. Human glomerular endothelium: interplay among glucose, free fatty acids, angiotensin II, and oxidative stress. Am J Physiol Renal Physiol 298: F125-F132, 2010. First published October 28, 2009; doi:10.1152/ajprenal.00248.2009.-Glomerular endothelial cells (GEC) are strategically situated within the capillary loop and adjacent to the glomerular mesangium. GEC serve as targets of metabolic, biochemical, and hemodynamic signals that regulate the glomerular microcirculation. Unequivocally, hyperglycemia, hypertension, and the local renin-angiotensin system partake in the initiation and progression of diabetic nephropathy (DN). Whether free fatty acids (FFA) and reactive oxygen species (ROS) that have been associated with the endothelial dysfunction of diabetic macrovascular disease also contribute to DN is not known. Since endothelial cells from different organs and from different species may display different phenotypes, we employed human GEC to investigate the effect of high glucose (22.5 mmol/l), FFA (800 mu mol/l), and angiotensin II (ANG II; 10(-7) mol/l) on the genesis of ROS and their effects on endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX-2), and the synthesis of prostaglandins (PGs). We demonstrated that high glucose but not high FFA increased the expression of a dysfunctional eNOS as well as increased ROS from NADPH oxidase (100%) and likely from uncoupled eNOS. ANG II also induced ROS from NADPH oxidase. High glucose and ANG II upregulated (100%) COX-2 via ROS and significantly increased the synthesis of prostacyclin (PGI(2)) by 300%. In contrast, FFA did not upregulate COX-2 but increased PGI(2) (500%). These novel studies are the first in human GEC that characterize the differential role of FFA, hyperglycemia, and ANG II on the genesis of ROS, COX-2, and PGs and their interplay in the early stages of hyperglcyemia.