Choice of a hemodynamic model for occlusive thrombosis in arteries

Intravascular thrombosis can lead to heart attacks and strokes that together are the leading causes of death in the US (Kochanek, K.D., Murphy, S.L., Xu, J.Q., 2014). The ability to identify the offending biofluid mechanical conditions and predict the timescale of thrombotic occlusion in vessels and devices may improve patient outcomes. A computational model was developed to describe the growth of thrombus based on the local hemodynamic shear rate. The model predicts thrombus deposition based on initial geometric and fluid mechanical conditions, which are updated throughout the simulation to reflect the changing lumen dimensions. Thrombus growth and occlusion from whole blood was measured in in vitro experiments using stenotic glass capillary tubes, a PDMS microfluidic channel, and a PTFE stenotic aorto-iliac graft. Comparison of the predicted occlusion times to experimental results shows excellent agreement. The results indicate that local shear rate plays a critical role in acute thrombosis, and that hemodynamic characterization may have clinical utility.     

纤维蛋白原与冠心病PCI介入治疗围术期心肌梗死的相关性

目的:探讨纤维蛋白原与冠心病介入治疗围术期心肌梗死的相关性。方法:2013年1月到2015年1月,选择在我院进行诊治的冠心病患者92例,都给予PCI介入手术治疗,在手术前后进行纤维蛋白原与心功能的测定,对围术期心肌梗死发生情况与临床资料进行调查与分析。结果:所有患者都介入手术治疗成功,术后LVESVI与LVEDVI值都明显低于术前(P0.05),而术后LVEF值明显高于术前(P0.05);术后患者的血浆纤维蛋白原值为3.66±0.42 g/L,明显低于术前的7.45±0.56 g/L(P0.05)。围手术期发生心肌梗死8例,发生率为8.7%。Spearman秩相关分析法结果显示心肌梗死发病与血浆纤维蛋白原、LVESVI、LVEDVI、LVEF值都存在明显相关性(P0.05),多元Logistic回归分析结果显示纤维蛋白原、LVESVI、LVEDVI、LVEF、年龄为导致冠心病围术期心肌梗死的主要危险因素(P0.05)。结论:介入手术治疗冠心病具有很好的效果,但是围术期心肌梗死的发生率比较高,纤维蛋白原能有效反应病变状况,在心肌梗死的发生发展中起着关键性作用。     

Conformational plasticity of ADAMTS13 in hemostasis and autoimmunity

A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) is a multidomain metalloprotease for which until now only a single substrate has been identified. ADAMTS13 cleaves the polymeric force-sensor von Willebrand factor (VWF) that unfolds under shear stress and recruits platelets to sites of vascular injury. Shear force–dependent cleavage at a single Tyr–Met peptide bond in the unfolded VWF A2 domain serves to reduce the size of VWF polymers in circulation. In patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), a rare life-threatening disease, ADAMTS13 is targeted by autoantibodies that inhibit its activity or promote its clearance. In the absence of ADAMTS13, VWF polymers are not adequately processed, resulting in spontaneous adhesion of blood platelets, which presents as severe, life-threatening microvascular thrombosis. In healthy individuals, ADAMTS13–VWF interactions are guided by controlled conversion of ADAMTS13 from a closed, inactive to an open, active conformation through a series of interdomain contacts that are now beginning to be defined. Recently, it has been shown that ADAMTS13 adopts an open conformation in the acute phase and during subclinical disease in iTTP patients, making open ADAMTS13 a novel biomarker for iTTP. In this review, we summarize our current knowledge on ADAMTS13 conformation and speculate on potential triggers inducing conformational changes of ADAMTS13 and how these relate to the pathogenesis of iTTP.     

Molecular and cellular events at the site of myocardial infarction: from the perspective of rebuilding myocardial tissue

The potential for bone marrow-derived progenitor cells (BMDPC) to regenerate myocardial tissue following infarction depends on homing, migration, nourishment, and spatially appropriate growth of BMDPC. Requisite to these objectives is the expression of adhesion molecules (ICAM-1) and chemoattractant cytokines (MCP-1), matrix metalloproteinase (MMP) activity, a neovasculature, and fibrillar collagen scaffolding. We found that enhanced ICAM-l and MCP-1, as well as MMP activity on day 3 and 7 postMI, are present to facilitate the homing, chemotaxis, and migration of circulating cells into the infarct site. The vascular network formed at the infarct site contains a ratio of conduit to exchange vessels that is greater than that for control tissue and therefore its ability to nourish BMDPC for their growth appears to be tenuous. These findings, together with the dense formation of a fibrillar collagen scar beyond week 2, suggest the optimal time to rebuild myocardium from BMDPC resides within 2 week postMI.