Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Nephrology, Danderyd University Hospital, Stockholm, Sweden.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Thromb Res. 2020 Dec;196:78-86. doi: 10.1016/j.thromres.2020.08.012. Epub 2020 Aug 9.
Patients with type 1 diabetes have high risk of developing microvascular complications, and microangiopathy contributes to premature cardiovascular disease in this population. The role that microvesicles (MVs) may play in the development of microangiopathy in type 1 diabetes remains unclear.
Plasma levels of endothelial MVs (EMVs) and platelet MVs (PMVs) in 130 patients with type 1 diabetes without microangiopathy, 106 patients with microangiopathy and 100 matched healthy controls were analyzed using flow cytometry. MV expression of procoagulant phosphatidylserine (PS) and proinflammatory high mobility group box-1 protein (HMGB1) was also assessed.
Patients with type 1 diabetes had markedly elevated levels of EMVs and PS+ EMVs as well as PMVs and PS+ PMVs compared to healthy controls (p < .001 for all). Furthermore, HMGB1+ EMVs and HMGB1+ PMVs were significantly increased in patients (p < .001 for all). After adjusting for potential confounders, there were no clear differences between patients with or without microvascular complications for any of the MV parameters.
Type 1 diabetes is a prothrombotic and proinflammatory disease state that, regardless of the presence of clinical microangiopathy, is associated with elevated levels of plasma MVs, in particular those of an endothelial origin. We have for the first time demonstrated that patients with type 1 diabetes have higher levels of HMGB1+ MVs. HMGB1 is an alarmin with potent proinflammatory effects that drive endothelial dysfunction, and it would therefore be of interest to further study the role of HMGB1+ MVs in the development of macrovascular complications in type 1 diabetes.
1 型糖尿病患者发生微血管并发症的风险较高,而微血管病变是该人群发生心血管疾病的早期原因。微泡(MVs)在 1 型糖尿病微血管病变的发展中可能起的作用尚不清楚。
使用流式细胞术分析了 130 例无微血管并发症的 1 型糖尿病患者、106 例有微血管并发症的患者和 100 例匹配的健康对照者的血浆内皮 MV(EMV)和血小板 MV(PMV)水平。还评估了 MV 表达的促凝磷脂酰丝氨酸(PS)和促炎高迁移率族蛋白 B1(HMGB1)。
与健康对照组相比,1 型糖尿病患者的 EMV 和 PS+ EMV 以及 PMV 和 PS+ PMV 水平明显升高(所有 p <.001)。此外,HMGB1+ EMV 和 HMGB1+ PMV 在患者中也显著增加(所有 p <.001)。在调整了潜在的混杂因素后,有或无微血管并发症的患者之间,任何 MV 参数均无明显差异。
1 型糖尿病是一种促凝和促炎的疾病状态,无论是否存在临床微血管并发症,都与血浆 MV 水平升高有关,特别是内皮起源的 MV 水平升高。我们首次证明 1 型糖尿病患者 HMGB1+ MV 水平更高。HMGB1 是一种具有潜在促炎作用的警报素,可导致内皮功能障碍,因此,进一步研究 HMGB1+ MV 在 1 型糖尿病大血管并发症发展中的作用将是有趣的。