Intima

Diseases. Liquid crystals have been impHcated in a number of disease conditions in the human body. A complex cholesterol—phosphoHpid—Hpoprotein Hquid crystal phase has been identified in the initiation and maintenance of atheromatous deposits on the aortic intima in dissected human and rabbit arteries (40). The paracrystalHne nature of this precursor to plaque buildup with the resultant loss of arterial elasticity... 

Meticulous care needs to be used in the application of this tissue adhesive. Only a very thin layer of adhesive should be used to assist with reapproximation of the intima and adventitia. It is important to remember that the material should not be allowed to drip into or onto critical areas such as the ostium of the coronary arteries. Inadvertent placement of this agent in such areas can result in blockage of a critical artery and a potentially fatal myocardial infarction. In addition. 

Acute coronary syndromes most often result from a physical disruption of the fibrous cap, either frank cap fracture or superficial endothelial erosion, allowing the blood to make contact with the thrombogenic material in the lipid core or the subendothelial region of the intima. This contact initiates the formation of a thrombus, which can lead to a sudden and dramatic blockade of blood flow through the affected artery. If the thrombus is nonocclusive or transient, it may either be clinically silent or manifest as symptoms characteristic of unstable angina. Importantly, if collateral vessels have previously formed, for example, due to chronic ischemia produced by multi vessel disease, even total occlusion of one coronary artery may not lead to an acute myocardial infarction. 

The innermost layer of an artery, which consists of loose connective tissue covered by a monolayer of endothelium that resides on a basement membrane. In human arteries, the intima often contains resident smooth muscle cells even early in life. Atherosclerotic plaques form in the intima. 

We have identified mast cells around blood vessels and between myocardial fibers in all sections of human hearts [16,17]. These cells are also seen in normal and atherosclerotic human arterial intima [ 18-21 ]. In situ electron microscopy of cardiac mast cells revealed a small percentage (about 5%) of activated, i.e. partially degranulated mast cells [16,22]. This is clinically relevant because it implies that immunologic and non-immunologic stimuli can activate HHMC to release vasoactive and proinflammatory mediators [23]. 

Kaartinen M, Penttila A, Kovanen PT Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation 1994 90 1669. Kaartinen M, Penttila A. Kovanen PT Mast cells of two types differing in neutral protease composition in the human aortic intima. Demonstration of tryptase- and tryptase/chymase-containing mast cells in normal intimas, fatty streaks, and the shoulder region of atheromas. Arterioscler Thromb 1994 14 966. 

With regard to epinephrines potential adverse cardiac effects, it is important to remember that in anaphylaxis, the heart is a target organ. Mast cells located between myocardial fibers, in perivascular tissue, and in the arterial intima are activated through IgE and other mechanisms to release chemical mediators of inflammation, including histamine, leukotriene C4, and prostaglandin D2. Coronary artery spasm, myocardial injury, and cardiac dysrhythmias have been documented in some patients before epinephrine has been injected for treatment of anaphylaxis, as well as in patients with anaphylaxis who have not been treated with epinephrine [11, 12]. 

The intima of the arterial wall contains hyaluronic acid and chondroitin sulfate, dermatan sulfate, and heparan sulfate proteoglycans. Of these proteoglycans, dermatan sulfate binds plasma low-density lipoproteins. In addition, dermatan sulfate appears to be the major GAG synthesized by arterial smooth muscle cells. Because it is these cells that profiferate in atherosclerotic lesions in arteries, dermatan sulfate may play an important role in development of the atherosclerotic plaque. 

Celia G, Scattolo N, Luzzato G, Stevanato E, Vio C, Girolami A. Effects on platelets and on the clotting system of four glycosaminoglycans extracted from hog mucosa and one extracted from aortic intima of the calf, J Med 1986 17 331-346. 

Inverse association. + = Positive association. 0 = No association. CHD = coronary heart disease. CVD = cardiovascular disease. Ml = myocardial infarction. IMT = intima media thickness. CCA-IMT = common carotid artery intima media thickness. LDL = low-density lipoprotein. 

Carotenoids and cardiovascular diseases — Numerous epidemiological studies aimed to study the relationship of carotenoids and cardiovascular diseases (CVDs) including coronary accident risk and stroke. It appeared then that observational studies, namely prospective and case-control studies, pointed to a protective effect of carotenoids on myocardial infarct and stroke, but also on some atherosclerosis markers such as intima media thickness (IMT) of the common carotid artery (CCA) and atheromatous plaque formation. 

Some prospective and case-control studies also investigated the relationship of carotenoids and the evolution of CCA-IMT. Although the EVA study showed no association between total carotenoids and IMT, others like the ARIC study, the Los Angeles Atherosclerosis Study, " and the Kuopio Ischaemic Heart Disease Risk Factor Study demonstrated the protective role of isolated carotenoids such as lycopene, lutein, zeaxanthin, and P-cryptoxanthin on IMT. Thus, findings from prospective and case-control studies have suggested that some carotenoids such as lycopene and P-carotene may present protective effects against CVD and particularly myocardial infarcts and intima media thickness, a marker of atherosclerosis. 

Although atherosclerosis and rheumatoid arthritis (RA) are distinct disease states, both disorders are chronic inflammatory conditions and may have common mechanisms of disease perpetuation. At sites of inflammation, such as the arterial intima undergoing atherogen-esis or the rheumatoid joint, oxygen radicals, in the presence of transition-metal ions, may initiate the peroxidation of low-density lipoprotein (LDL) to produce oxidatively modified LDL (ox-LDL). Ox-LDL has several pro-inflammatory properties and may contribute to the formation of arterial lesions (Steinberg et /., 1989). Increased levels of lipid peroxidation products have been detected in inflammatory synovial fluid (Rowley et /., 1984 Winyard et al., 1987a Merry et al., 1991 Selley et al., 1992 detailed below), but the potential pro-inflammatory role of ox-LDL in the rheumatoid joint has not been considered. We hypothesize that the oxidation of LDL within the inflamed rheumatoid joint plays a pro-inflammatory role just as ox-LDL has the identical capacity within the arterial intima in atherosclerosis. 

In atherosclerosis, ox-LDL is taken up ultimately by macrophages and smooth muscle cells in the arterial intima. Once loaded with lipid, these cells have a foamy appearance when examined histologically. The accumulation of these so-called foam cells in the artery wall leads to the formation of fatty streaks , which can lead to atheromatous plaque formation and consequent coronary heart disease. 

Yagi, K., Ohkawa, H., Oshistii, N., Yamashita, M. and Nakashima, T. (1981). Lesion of aortic intima caused by intravenous administration of linoleic hydroperoxide. J. Appl. Biochem. 3, 58-61. 

The normal arterial wall consists of the intima, media, and adventitia, as illustrated in Fig. 4—3A. The endothelium is located in the intima and consists of a layer of endothelial cells that line the lumen of the artery and form a selective barrier between the vessel wall and blood contents. The internal elastic lamina separates the intima and media, where vascular smooth muscle cells are found. The vascular adventitia comprises the artery s outer layer. Atherosclerotic lesions form in the subendothelial space between the endothelial cells and internal elastic lamina. 

Dysfunction of the endothelium allows lipoproteins, predominantly low-density lipoprotein (LDL) cholesterol, and inflammatory cells, namely monocytes and T lymphocytes, to migrate from the plasma to the sub-endothelial space. Monocyte-derived macrophages ingest lipoproteins to form foam cells. Macrophages also secrete growth factors that promote smooth muscle cell migration from the media to the intima. A fatty streak consists of lipid-laden macrophages and smooth muscle cells and is the earliest type of atherosclerotic lesion. 

Intima The inner layer of the wall of an artery or vein. 

In Apo E-deficient animals fed a normal chow diet, fatty streaks are first observed in the proximal aorta at 10 to 12 weeks (15). The xanthoma that forms in the intima contains foam cells and is often called the early atherosclerotic lesion and is critically dependent on monocytes. Smooth muscle cells (SMCs) arrive in the intima at approximately 15 weeks and form a fibrous cap around 20 weeks (16). By 36 weeks, lumen narrowing occurs in the external branches of the carotid artery (incidence -75%), but the lumen size is maintained in the aorta. Lumen narrowing, or stenosis, does not correlate with plaque size but... 

Evidence implicating CX3CR1 and fractalkine in atherosclerosis is growing. Immunohistochemical analysis of human atherosclerotic lesions demonstrate that macrophages in the intima as well as smooth muscle cells, mononuclear cells, and foam cells in the deep intima and media express CX3CL1, whereas normal arteries do not (57,58). 

It has been already pointed out that nitric oxide exhibits antioxidant effect in LDL oxidation at the NO/ 02 ratio 1. Under these conditions the antioxidant effect of NO prevails on the prooxidant effect of peroxynitrite. Although some earlier studies suggested the possibility of NO-mediated LDL oxidation [152,153], these findings were not confirmed [154]. On the other hand, at lower values of N0/02 ratio the formed peroxynitrite becomes an efficient initiator of LDL modification. Beckman et al. [155] suggested that peroxynitrite rapidly reacts with tyrosine residues to form 3-nitrotyrosine. Later on, Leeuwenburgh et al. [156] found that 3-nitrotyrosine was formed in the reaction of peroxynitrite with LDL. The level of 3-nitrotyrosine sharply differed for healthy subjects and patients with cardiovascular diseases LDL isolated from the plasma of healthy subjects contained a very low level of 3-nitrotyrosine (9 + 7 pmol/mol 1 of tyrosine), while LDL isolated from aortic atherosclerotic intima had a 90-fold higher level (840 + 140 pmol/moD1 of tyrosine). It has been proposed that peroxynitrite formed in the human artery wall is able to promote LDL oxidation in vivo. 

Only fragmentary information exists in the human. In a study on 27 postmenopausal women with breast cancer, tamoxifen slightly slowed the progression of atherosclerosis as assessed by changes in carotid intima-media thickness (Stamatelopoulos et al. 2004). 

Stamatelopoulos KS, Lekakis JP, Poulakaki NA, Papamichael CM, Venetsanou K, Az-naouridis K, Protogerou AD, Papaioannou TG, Kumar S, Stamatelopoulos SF (2004) Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women. Am Heart J 147 1093-1099... 

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