Molecular Changes in the Hypoxic Endothelium
Gene expression patterns in endothelial cells (EC), presumably including those of the valve cusp parietalis, change in response to hypoxia and other challenges. These changes, the signalling networks involved and the consequences for cell phenotype have been elucidated in considerable detail, providing a mechanistic underpinning for our hypothesis (the VCHH) of the aetiology of DVT. In particular, they define mechanisms for (1) the increased congregation and anchoring of leukocytes and platelets on the hypoxic area, (2) the effects of activated neutrophils on the injured vascular endothelium, and (3) enhanced blood coagulation in the immediate neighbourhood. A significant part of the molecular-biological literature in this field concerns the effects of hypoxia on vasodynamics, which have limited relevance to the aetiology of DVT but may be pertinent to perfusion of the vessel wall via the vasa venarum. Satisfactory assimilation of these ‘mechanistic’ findings into the VCHH, as articulated in Chapter 11, exemplifies the reconciliation of approaches to medicine and biology outlined in the preface and discussed further in Chapters 4 and 5. We return to this fundamental point at the end of the present chapter and in the appendix.
KeywordsEndothelial cell phenotype elk-1/egr-1 signalling pathway proteinase-activated receptor platelet activation leukocytes
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