Kövamees Oskar, Shemyakin Alexey, Pernow John
Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden Department of Cardiology Karolinska University Hospital, Stockholm, Sweden
Unit of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden Department of Cardiology Karolinska University Hospital, Stockholm, Sweden.
Diab Vasc Dis Res. 2016 Sep;13(5):354-60. doi: 10.1177/1479164116643916. Epub 2016 May 13.
Endothelial dysfunction contributes to the development of vascular complication in diabetes. Arginase has emerged as a key mechanism behind endothelial dysfunction by its reciprocal regulation of nitric oxide production by substrate competition. We hypothesized that increased arginase activity in patients with type 2 diabetes shifts the metabolism of l-arginine from nitric oxide synthase to arginase resulting in an increase in the plasma ratio of ornithine/citrulline, and that this ratio is associated with endothelial dysfunction.
Forearm endothelium-dependent vasodilatation and endothelium-independent vasodilatation were determined in 15 patients with type 2 diabetes and 10 healthy controls and related to amino acids reflecting arginase and nitric oxide synthase activity.
Compared to healthy controls, patients with diabetes had impaired endothelium-dependent vasodilatation and endothelium-independent vasodilatation. The ratios of ornithine/citrulline and proline/citrulline were 60% and 95% higher, respectively, in patients with diabetes than in controls (p < 0.001). The plasma ornithine/arginine ratio was 36% higher in patients with diabetes, indicating increased arginase activity. These ratios were inversely correlated to endothelium-dependent vasodilatation and endothelium-independent vasodilatation.
Patients with diabetes and macrovascular complications have increased amino acid ratios reflecting a shift in arginine metabolism due to arginase activation. These changes are inversely related to endothelial function supporting that arginase activity contributes to endothelial dysfunction.
内皮功能障碍促进糖尿病血管并发症的发生。精氨酸酶通过底物竞争对一氧化氮生成的相互调节，已成为内皮功能障碍背后的关键机制。我们假设2型糖尿病患者精氨酸酶活性增加会使L-精氨酸的代谢从一氧化氮合酶转向精氨酸酶，导致血浆鸟氨酸/瓜氨酸比值升高，且该比值与内皮功能障碍相关。
测定了15例2型糖尿病患者和10名健康对照者的前臂内皮依赖性血管舒张和非内皮依赖性血管舒张，并将其与反映精氨酸酶和一氧化氮合酶活性的氨基酸相关联。
与健康对照相比，糖尿病患者的内皮依赖性血管舒张和非内皮依赖性血管舒张受损。糖尿病患者的鸟氨酸/瓜氨酸比值和脯氨酸/瓜氨酸比值分别比对照组高60%和95%（p < 0.001）。糖尿病患者的血浆鸟氨酸/精氨酸比值高36%，表明精氨酸酶活性增加。这些比值与内皮依赖性血管舒张和非内皮依赖性血管舒张呈负相关。
患有糖尿病和大血管并发症的患者氨基酸比值升高，反映出由于精氨酸酶激活导致精氨酸代谢发生改变。这些变化与内皮功能呈负相关，支持精氨酸酶活性导致内皮功能障碍。
