Vascular endothelium, damage

Normally, quiescent platelets freely circulate through the vasculature, reflective of the hemocompatible character of the vascular endothelium and the anti-thrombotic nature of healthy human blood vessels. Traumatic vascular damage incites a spatially and temporally coordinated platelet transformation encompassing several major, sequential phenotypic changes platelet adhesion to subendothelial matrix components... 

Platelets are considered as the key factors in arterial thrombosis recent studies indicate that they have an important regulatory role as the source of inflammatory mediators and directly initiate (Fig. 8) an inflammatory response of the vessel wall. Platelet and leukocyte recruitment on subendothelial cells is the early mechanism of vascular inflammatory damage. After vascular injury denudation of the endothelium and platelet adhesion, other blood cells are recruited erythrocytes release ADP and leukocyte infiltration occurs by their... 

Interaction and adhesion of biological surfaces are central considerations for other physiological conditions as well. Platelets, erythrocytes, the vascular endothelium and other tissues interact during thrombosis and hemostasis. Also, when erythrocytes come in contact with artificial surfaces, damage often occurs and blood trauma may result. Finally, the accumulation of cholesterol deposits on the interior walls of arteries is responsible for atherosclerosis. 

The authors noted that thrombotic microangiopathy due to cocaine is fairly rare. Its pathogenesis is unclear, possible mechanisms being an immune reaction or direct damage to the vascular endothelium. Cocaine-induced acute hepatitis has been linked to several toxic metabolites, including norcocaine and N-hydroxynorcocaine, which are produced by cytochrome P450 enzymes. 

Gurrent theories are that arterial damage caused by hypertension and/ or hypercholesterolemia induces release of MCP-1/CGL2 from vascular endothelium or smooth muscle cells (Gerard and Rollins, 2001). The... 

Platelets are actively involved in the process of hemostasis, by which any break in the vascular endothelium is rapidly repaired without compromising the fluidity of the blood. In response to injury, platelets adhere to the subendothelial matrix of a damaged vessel, spread over the surface, and recruit additional platelets within a developing platelet aggregate or thrombus. Whereas hemostasis is a normal physiological response to endothelial wound repair, improper regulation or overreactivity of this system can lead to the pathological condition of thrombosis. 

As the knowledge of the pathogenesis of atherosclerosis rapidly increases, it appears that an active vascular endothelium, smooth muscle cells, and blood-borne cells such as monocytes and macrophages all play active roles in the atherosclerotic disease process. Risk factors, such as elevated plasma levels of certain lipids, prooxidants, and cytokines, may contribute to the chronic activation/stimulation as well as to the damage of the endothelium and other vascular tissues (160). There is evidence that supports the hypothesis that it is not only pure cholesterol and saturated fats but rather oxidation products of cholesterol and unsaturated fats (and possibly certain pure unsaturated fats) that are atherogenic, possibly by causing endothelial cell injury/dysfiinction. Lipid-mediated endothelial cell dysfunction may lead to adhesion of monocytes, increased permeability of the endothelium to macromolecules, i.e., a decrease in endothelial barrier function, and disturbances in growth control of the vessel wall. 

In adults, a severe form of lung injury can develop in association with sepsis, pneumonia, and injury to the lungs due to trauma or surgery. This catastrophic disorder is known as acute respiratory distress syndrome (ARDS) and has a mortality rate of more than 40%. In ARDS, one of the major problems is a massive influx of activated neurophils which damage both vascular endothelium and alveolar epithelium and result in massive pulmonary edema and impairment of surfactant function. Neutrophil proteinases (e.g., elastase) break down surfactant proteins. A potential therapeutic strategy in ARDS involves administration of both surfactant and antiproteinases (e.g., recombinant a I -antitrypsin). 

A number of other mechanisms may contribute to the development of NSAID-induced mucosal injury. Neutrophil adherence may damage the vascular endothelium and may lead to a reduction in mucosal blood flow, or may liberate oxygen-derived free radicals and proteases. Leukotrienes, products of lipoxygenase metabolism, are inflammatory substances that may contribute to mucosal injury through stimulatory effects on neutrophil adherence (see Fig. 33-3). 

Hyperacute rejection may occur when preformed donor-specific antibodies are present in the recipient at the time of the transplant and may be evident within minutes of the transplant procedure. Hyperacute rejection can be induced by immunoglobulin G (IgG) antibodies that bind to antigens on the vascular endothelium, such as class I MHC, ABO, and vascular endothelial cell antigens. Tissue damage can be mediated through antibody-dependent, cell-mediated cytotoxicity or through activation of the complement cascade. The ischemic damage to the microvasculature rapidly produces tissue necrosis. 

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