Vascular injuries

In the vasculature, ANG H not only increases contraction of smooth muscle cells, but is also able to induce vascular injury. This can be prevented by blocking NFkB activation [3] suggesting a link between ANG II and inflammation processes involved in the pathogenesis of arteriosclerosis (see below). Thus, ACE inhibitors not only decrease vascular tone but probably also exert vasoprotective effects. 

The red thrombus consists primarily of red cells and fibrin. It morphologically resembles the clot formed in a test tube and may form in vivo in areas of retarded blood flow or stasis (eg, veins) with or without vascular injury, or it may form at a site of injury or in an abnormal vessel in conjunction with an initiating platelet plug. 

Venous thromboembolism (VTE) is one of the most common cardiovascular disorders in the United States. VTE is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE) resulting from thrombus formation in the venous circulation (Fig. 7-1).1 It is often provoked by prolonged immobility and vascular injury and is most frequently seen in patients who have been hospitalized for a serious medical illness, trauma, or major surgery. VTE can also occur with little or no provocation in patients who have an underlying hypercoagulable disorder. 

The presence of protein in the urine is a marker of glomerular and tubular dysfunction and is recognized as an independent risk factor for the progression of CKD.8 Furthermore, the degree of proteinuria correlates with the risk for progression of CKD. An increase of 1 g of protein excretion per day is associated with a five-fold increase in the risk of progression of CKD, regardless of the cause of CKD.9 The mechanisms by which proteinuria potentiates CKD are discussed later. Microalbuminuria is also linked with vascular injury and increased cardiovascular mortality.10... 

U1. Uchiba, M., Okajima, K Murakami, K., Nawa, K., Okabe, H and Takatsuki, K., Recombinant human soluble thrombomodulin reduces endotoxin-induced pulmonary vascular injury via protein C activation in rats. Thromb. Haemost. 74, 1265-1270 (1995). 

The congregation and clumping of blood platelets at the site of vascular injury, thus effectively plugging the site of blood leakage. 

The initial steps of the intrinsic pathway are somewhat more complicated. This system requires the presence of clotting factors VIII, IX, XI and XII, all of which, except for factor VIII, are endo-acting proteases. As in the case of the extrinsic pathway, the intrinsic pathway is triggered upon exposure of the clotting factors to proteins present on the surface of body tissue exposed by vascular injury. These protein binding/activation sites probably include collagen. 

Prothrombin (factor II) is a 582 amino acid, 72.5 kDa glycoprotein, which represents the circulating zymogen of thrombin (Ha). It contains up to six y-carboxyglutamate residues towards its N-terminal end, via which it binds several Ca2+ ions. Binding of Ca2+ facilitates prothrombin binding to factor Xa at the site of vascular injury. The factor Xa complex then proteolytically... 

Vascular injury may result from major orthopedic surgery (e.g., knee and hip replacement), trauma (especially fractures of the pelvis, hip, or leg), or indwelling venous catheters. 

Savolainen-Peltonen H, Luoto NM, Kangas L, Hayry P (2004) Selective estrogen receptor modulators prevent neointima formation after vascular injury. Mol Cell Endocrinol 227 9-20... 

Yue TL, Vickery-Clark L, Louden CS, Gu JL, Ma XL, Narayanan PK, Li X, Chen J, Storer B, Willette R, Gossett KA, Ohlstein EH (2000) Selective estrogen receptor modulator idoxifene inhibits smooth muscle cell proliferation, enhances reendothelial-ization, and inhibits neointimal formation in vivo after vascular injury. Circulation 102(Suppl 3) III281—288... 

Since Lp(a) binds to fibrin, it can be directed to sites of fibrin deposition (vascular injury), providing a high concentration of cholesterol-rich lipoprotein that then can be taken up by macrophages via their scavenger receptors. This... 

Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am. J. Pathol. 147 267-77. 

Other agents such as actinomycin D, C-Myc antisense, dexamethasone, and matrix metalloproteinase inhibitors, aimed at altering inflammatory and smooth muscle actions in the biological repair response to vascular injury, are being evaluated. The success of these devices depends upon multiple issues, including stent platform, carrier, drug properties, and pharmacokinetic profile (18-26). Large randomized, controlled trials, demonstrate a restenosis rate of 5% to 10% with DES (27). 

Innate immunity plays a central role in vascular injury and repair. Suppression of monocyte numbers by IV infusion of LBPs inhibits intimal hyperplasia after balloon injury (52,99,100). The preprocedural activation... 

Rogers C, Tseng DY, Squire JC, Edelman ER. Ballon-artery interactions during stent placement a finite element analysis approach to pressure, compliance, and stent design as contributors to vascular injury. Circ Res 1999 84 378-383. 

Welt E, Tso C, Edelman E, et al. Leukocyte recruitment and expression of chemokines following different forms of vascular injury. Vase Med 2003 8 1-7. 

Upon vascular injury, the coagulation system is activated thrombocytes and fibrin molecules coalesce into a plug ... 

The intravascular pathway (left) is probably also triggered by vascular injuries. It... 

Thrombin, a serine protease, cleaves fibrinogen into fibrin to create a fibrous plug and also amplifies its own production through the activation of factor XI and cofactors V and Vlll. Thrombin also plays a crucial role in the activation of platelets through the cleavage of the protease-activated receptors on the platelet surface. Antagonists of G-protein-coupled protease-activated receptor PARi have been synthesised to study the role of thrombin PARi receptor in thrombosis and vascular injury. Thrombosis is the most common cause of death in the industrialised world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of... 

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