Department of Physiological Sciences, Stellenbosch University, Stellenbosch Private Bag X1 MATIELAND, 7602, Stellenbosch, South Africa.
Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, 0007, South Africa.
Sci Rep. 2017 Aug 29;7(1):9680. doi: 10.1038/s41598-017-09860-4.
Type 2 diabetes (T2D) has many cardiovascular complications, including a thrombotic propensity. Many such chronic, inflammatory diseases are accompanied (and may be exacerbated, and possibly even largely caused) by amyloid fibril formation. Recognising that there are few strong genetic associations underpinning T2D, but that amyloidogenesis of amylin is closely involved, we have been seeking to understand what might trigger the disease. Serum levels of bacterial lipopolysaccharide are raised in T2D, and we recently showed that fibrin(ogen) polymerisation during blood clotting can be affected strongly by LPS. The selectivity was indicated by the regularisation of clotting by lipopolysaccharide-binding protein (LBP). Since coagulopathies are a hallmark of T2D, we wondered whether they might too be caused by LPS (and reversed by LBP). We show here, using SEM and confocal microscopy, that platelet-poor-plasma from subjects with T2D had a much greater propensity for hypercoagulability and for amyloidogenesis, and that these could both be reversed by LBP. These data imply that coagulopathies are an important feature of T2D, and may be driven by 'hidden' LPS. Given the prevalence of amyloid formation in the sequelae of diabetes, this opens up novel strategies for both the prevention and treatment of T2D.
2 型糖尿病（T2D）有许多心血管并发症，包括血栓倾向。许多此类慢性炎症性疾病伴随着（并且可能加剧，甚至可能在很大程度上由）淀粉样纤维形成。鉴于 T2D 几乎没有强有力的遗传关联，但胰岛淀粉样肽的淀粉样形成密切相关，我们一直在努力了解可能引发该疾病的原因。T2D 患者的血清细菌脂多糖水平升高，我们最近表明，血液凝固过程中的纤维蛋白（原）聚合可以被脂多糖强烈影响。这种选择性是由脂多糖结合蛋白（LBP）对凝血的正则化所表明的。由于凝血异常是 T2D 的一个标志，我们想知道它们是否也可能由 LPS（并被 LBP 逆转）引起。我们在这里使用 SEM 和共聚焦显微镜显示，来自 T2D 患者的血小板贫血浆具有更高的高凝倾向和淀粉样形成倾向，而这些都可以被 LBP 逆转。这些数据表明凝血异常是 T2D 的一个重要特征，并且可能由“隐藏”的 LPS 驱动。鉴于糖尿病后遗症中淀粉样形成的普遍性，这为 T2D 的预防和治疗开辟了新的策略。
