Arterial wall

The state of knowledge in the early 1990s of the effects of fat on health lacks clarity and general agreement. There is great support for the thesis that fully saturated fats are associated with problems of atherosclerosis and arterial fatty deposit, but there is evidence that stearates, which are saturates, are only poorly utilized in human digestion. Another body of work has estabUshed a connection between unsaturated fatty acids and a better state of arterial health and lowered fat body attachment to the arterial wall (23) contrary evidence exists that highly unsaturated fats polymerize more readily and thus contribute to arterial plaque formation. 

The saturated fatty acids, stearic [57-11-4] and palmitic [57-10-3], are found in animal fats and dairy products. Extensive studies point to the deleterious effect of these acids on arterial walls as a result it is recommended that saturated fatty acid intake be carefully controlled and intake limited (23). 

Laser ablation systems hold considerable promise if restenosis (reblocking of the arteries) rates are reduced. The rate as of 1995 is 30%, typically within six months. Mechanical or atherectomy devices to cut, shave, or pulverize plaque have been tested extensively in coronary arteries. Some of these have also been approved for peripheral use. The future of angioplasty, beyond the tremendous success of conventional balloon catheters, depends on approaches that can reduce restenosis rates. For example, if appHcation of a dmg to the lesion site turns out to be the solution to restenosis, balloon catheters would be used for both dilating the vessel and deUvering the dmg. An understanding of what happens to the arterial walls, at the cellular level, when these walls are subjected to the various types of angioplasty may need to come first. 

Corona.iy Hea.rt Disea.se, A theory for atherogenesis (120) has been developed whereby oxidation of low density Hpoprotein (LDL) within the arterial wall is the critical first step. It has been hypothesized that sufficient intake of antioxidants would prevent oxidation of LDL and reduce development of coronary heart disease (122). Interest in determining the role of antioxidants in blocking LDL oxidation has led to the development of in vitro test systems. 

Calcium Channel Blockers. Because accumulation of calcium is one of the facets of the mote involved process leading to atherosclerosis, it would foUow that the antihypertensive calcium channel blockers might be effective in preventing atheroma. Both verapamil (Table 1) and nifedipine (Table 3) have been shown to stimulate the low density Upoprotein (LDL) receptor (159). This specific receptor-mediated pathway could theoretically improve Upid metaboUsm in the arterial wall, and thereby prove antiatherogenic. These effects have been proven in animals. 

Atherosclerosis is a degenerative disease which is characterized by cholesterol-containing thickening of arterial walls. Saturated fatty acids, high levels of cholesterol, elevated blood pressure, and elevated serum lipoprotein are well-knowm risk... 

Cholesterol is a principal component of animal cell plasma membranes, and much smaller amounts of cholesterol are found in the membranes of intracellular organelles. The relatively rigid fused ring system of cholesterol and the weakly polar alcohol group at the C-3 position have important consequences for the properties of plasma membranes. Cholesterol is also a component of lipoprotein complexes in the blood, and it is one of the constituents oiplaques that form on arterial walls in atherosclerosis. 

One source of calcium ions, which cause contraction of smooth muscle in arterial walls, is inflow through ion-specific channels. So, the calcium blockers block the channels, limiting inflow of calcium and keeping muscle cells in relaxed states for a longer time. 

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. 

Acute anticoagulation is widely used in the acute setting of arterial dissection. Once again, the rationale is to prevent propagation of local thrombosis and formation of new thrombus at the site of the injured arterial wall, which is beheved to reduce the likelihood of early stroke recurrence. This practice, while rational, is based on anecdotal evidence and case series, as randomized controlled trials have... 

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

IN CULTURE BY CELLS OF TYPE LOCATED IN ARTERY WALL... 

The lag-phase measurement at 234 nm of the development of conjugated dienes on copper-stimulated LDL oxidation is used to define the oxidation resistance of different LDL samples (Esterbauer et al., 1992). During the lag phase, the antioxidants in LDL (vitamin E, carotenoids, ubiquinol-10) are consumed in a distinct sequence with a-tocopherol as the first followed by 7-tocopherol, thereafter the carotenoids cryptoxanthin, lycopene and finally /3-carotene. a-Tocopherol is the most prominent antioxidant of LDL (6.4 1.8 mol/mol LDL), whereas the concentration of the others 7-tocopherol, /3-carotene, lycopene, cryptoxanthin, zea-xanthin, lutein and phytofluene is only 1/10 to 1/300 of a-tocopherol. Since the tocopherols reside in the outer layer of the LDL molecule, protecting the monolayer of phospholipids and the carotenoids are in the inner core protecting the cholesterylesters, and the progression of oxidation is likely to occur from the aqueous interface inwards, it seems reasonable to assign to a-tocopherol the rank of the front-line antioxidant. In vivo, the LDL will also interact with the plasma water-soluble antioxidants in the circulation, not in the artery wall, as mentioned above. 

Antibodies that recognize oxidized LDL but not native LDL show positive reactivity in human or animal atherosclerotic lesions, but not the normal arterial wall (Haberland etal., 1988 Palinski et al., 1989, 1990 Rosenfeld etal., 1990). 

Ross, R (1981). Atherosclerosis a problem of the biology of arterial wall cells and their interactions with blood components. Arteriosclerosis 1, 293-311. 

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