Shear Stress and Endothelial Mechanotransduction in Trauma Patients with Hemorrhagic Shock: Hidden Coagulopathy Pathways and Novel Therapeutic Strategies

被引:10
|
作者
Chalkias, Athanasios [1 ,2 ]
机构
[1] Univ Penn, Inst Translat Med & Therapeut, Perelman Sch Med, Philadelphia, PA 19104 USA
[2] Outcomes Res Consortium, Cleveland, OH 44195 USA
关键词
blood flow; microcirculation; endothelium; endothelial cell; mechanotransduction; mechanosensing; coagulation; translational research; critical care medicine; centhaquine; ISCHEMIA-REPERFUSION INJURY; WEIBEL-PALADE BODIES; PLASMINOGEN-ACTIVATOR; COAGULATION FUNCTION; HEPARAN-SULFATE; FACTOR-VIII; BLOOD-FLOW; SYMPATHOADRENAL ACTIVATION; PLATELET-FUNCTION; OXIDATIVE STRESS;
D O I
10.3390/ijms242417522
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Massive trauma remains a leading cause of death and a global public health burden. Post-traumatic coagulopathy may be present even before the onset of resuscitation, and correlates with severity of trauma. Several mechanisms have been proposed to explain the development of abnormal coagulation processes, but the heterogeneity in injuries and patient profiles makes it difficult to define a dominant mechanism. Regardless of the pattern of death, a significant role in the pathophysiology and pathogenesis of coagulopathy may be attributed to the exposure of endothelial cells to abnormal physical forces and mechanical stimuli in their local environment. In these conditions, the cellular responses are translated into biochemical signals that induce/aggravate oxidative stress, inflammation, and coagulopathy. Microvascular shear stress-induced alterations could be treated or prevented by the development and use of innovative pharmacologic strategies that effectively target shear-mediated endothelial dysfunction, including shear-responsive drug delivery systems and novel antioxidants, and by targeting the venous side of the circulation to exploit the beneficial antithrombogenic profile of venous endothelial cells.
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页数:23
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