Microvasculature

A number of inhibitors directed towards the active site of PKC have been developed [4]. Many of these have therapeutic potential and some are in clinical trials. The drug enzastaurin (LY317615) shows selectivity towards inhibiting PKC 3 and is currently in clinical trials for cancer. This drug has particular potential as a treatment for colon cancer because of the specific role ofPKC (311 in this disease (see above). A separate PKC (3 inhibitor, ruboxistaurin (LY333531) has been developed as a drug to treat the microvasculature complications of diabetes hyperactivation of both PKC (311 and PKC (31 contribute to diabetic retinopathy and microvasculature complications. 

Absent Grenz zone, loss of elastic fibers, elastogenesis, decreased thickness, microvasculature normal, no evidence of inflammation... 

Oxidatively modified LDL up-regulates the surfece expression of VCAM-1 and intracellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells, promoting the interactions between both cell types (Kume et al., 1992). This may play a pivotal role in the development of atherosclerosis by promoting the penetration of circulating monocytes into the suben-dothelial space whilst inhibiting the mobility of resident macrophages. It has been previously demonstrated that ICAM-1, E-selectin, and VCAM-1 are up-regulated in the microvasculature of rheumatoid but not control synovium (Corkill et al., 1991 Koch et al., 1991). The association between ox-LDL and increased expression of adhesion molecules in the inflamed synovium has yet to be studied. 

There is a long-standing hypothesis that the microvasculature plays a pathological role in forms of chronic inflammatory polyarthritis, particularly RA (Rothschild and Masi, 1982). One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. Blake et al. (1985) have su ested that the vascular abnormalities associated with RA may be linked to oxidized lipoproteins because they are cytotoxic to endothelial cells. 

Hernandez, L.A., Grisham, M.B. and Granger, D.N. (1987). A role for iron in oxidant-mediated ischaemic injury to intestinal microvasculature. Am. J. Physiol. 253, G49-G53. 

Importantly, over the past decade it has been demonstrated that chemokines and chemokine receptors are not restricted to leukocytes. In the brain, chemokine receptors are not only found in microglia and astrocytes but also in oligodendrocytes, neurons, and along the brain microvasculature. In this chapter, we will focus on the functions of chemokine receptors expressed by resident CNS cells during physiologic and inflammatory conditions. 

There are also numerous important variations in the microvasculature bed (i.e., arterioles, capillaries, and venules) that affect permeability. For example, venular portions of the capillaries have thin endothelial cells (170 nm), with frequent interendothelial discontinuities. About 30% of venular junctions are believed to have gaps of about 6 nm. Arterioles, in contrast, have endothelial cells that are linked by the tight junctions and communicating junctions, whereas the capillary endothelium contains... 

Microvasculature abnormal Blood vessels dilated, twisted... 

Pericytes lie periendothelially on the abluminal side of the microvessels (Figure 15.3). A layer of basement membrane separates the pericytes from the endothelial cells and the astrocyte foot processes. Pericytes send out cell processes which penetrate the basement membrane and cover around 20-30% of the micro-vascular circumference [18]. Pericyte cytoplasmic projections encircling the endothelial cells provide both a vasodynamic capacity and structural support to the microvasculature. They bear receptors for vasoactive mediators such as catecholamines, endothelin-1, VIP, vasopressin and angiotensin II. Pericytes become mark-... 

Drewes LR. Molecular architecture of the brain microvasculature. J Mol Neurosci 2001 16 93-98. 

Virgintino D, Monaghan P, Robertson D, Errede M, Bertossi M, Ambros-si G et al. An immunohistochemical and morphometric study on astrocytes and microvasculature in the human cerebral cortex. Histochem J 1997 29 655-660. 

Moreover, COX-2 expression seems to be regulated by synaptic activity [36]. Recently, COX-3 was characterized as generated from COX-1 intron-1 retention [37]. COX-3 is expressed in brain [37], brain microvasculature [38] and has been proposed to be a target of the analgesic/ antipyretic acetaminophen [37,39]. 

Interaction with other biological surfactants might add to clearance and lipoplex inactivation. Size of the particles plays a major role because extensive microvasculature of the lung leads to pulmonary clearance of larger particles by capillary bed deposition. Vascularization was identified as the main... 

---