Atherosclerosis

Atherosclerosis is a pathogenic response of the intima of the arterial vessel walls to noxious stimuli. It is characterized by lipids depositing in the vessel walls, which leads to wall narrowing. This can progress to IHD. Exposure to arsenic in drinking water is associated with an increased prevalence of carotid atherosclerosis in a dose-response relationship. In a cross-sectional study, Wang et al. (2002) assessed 

Various animal species have been exploited in experimental atherosclerosis research, but nowadays most of the research is performed in mice [139]. This species has the advantage of developing atherosclerotic lesions in a relatively short period of time. The emergence of a broad variety of knock-out and transgenic mouse strains has led to a huge increase in the atherosclerosis research performed in this species. Mice are resistant to atherosclerosis when fed a normal low-fat chow diet, but they can develop atherosclerotic lesions after hypercholes-terolaemia has been induced. The three most widely used models in research on atherosclerosis are diet-induced, apoE deficiency-induced or LDL receptor deficiency-induced [139]. 

Rabbits are the second most used species in this type of research, in particular the LDL receptor deficient Watanabe heritable hyperlipidaemic rabbits. These animals show expression of VCAM-1 in atherosclerotic lesions [140], but resemblance to human lesions is generally low [139,141]. 

A CARS image at 2850 cm was collected from the intima and enables to visualize plaque deposits. CARS microscopy offers an inherent confocality because the signal is generated only in a small volume. This property is demonstrated by depth profiles along the blue and green lines that gave signals up to 50 pm tissue depth. 

The plaque deposits are just a few micrometers thick at these locations. The fibrillar structures, distribution of lipids, and smoothness of the surface were different for intima of control arteries as studied in CARS images at 2930 cm [83]. 

The examples, references, and an early review [86] demonstrated that more FT-IR than Raman imaging studies of soft tissue were reported. This is mainly due to 

Although in its early stages, one can be optimistic that vibrational spectroscopic imaging has the potential to be fully accepted as a diagnostic tool for soft tissues with sufficient sensitivity and specificity for rapid and nondestructive in vitro, ex vivo, and in vivo analyses. 

Krafft, C, Dietzek, B., Schmitt, M., and Popp, J. (2012) Raman and coherent anti-Stokes Raman scattering microspectroscopy for biomedical applications. /. Biomed. Opt, 17, 040801. 

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Cholesterol is the central compound m any discussion of steroids Its name is a combination of the Greek words for bile (chole) and solid (stereos) preceding the characteristic alcohol suffix ol It is the most abundant steroid present m humans and the most important one as well because all other steroids arise from it An average adult has over 200 g of cholesterol it is found m almost all body tissues with relatively large amounts present m the brain and spinal cord and m gallstones Cholesterol is the chief constituent of the plaque that builds up on the walls of arteries m atherosclerosis... 

Cholesterol is biosynthesized in the liver trans ported throughout the body to be used in a va riety of ways and returned to the liver where it serves as the biosynthetic precursor to other steroids But cholesterol is a lipid and isn t soluble in water How can it move through the blood if it doesn t dis solve in if The answer is that it doesn t dissolve but IS instead carried through the blood and tissues as part of a lipoprotein (lipid + protein = lipoprotein) The proteins that carry cholesterol from the liver are called low density lipoproteins or LDLs those that return it to the liver are the high-density lipoproteins or HDLs If too much cholesterol is being transported by LDL or too little by HDL the extra cholesterol builds up on the walls of the arteries caus mg atherosclerosis A thorough physical examination nowadays measures not only total cholesterol con centration but also the distribution between LDL and HDL cholesterol An elevated level of LDL cholesterol IS a risk factor for heart disease LDL cholesterol is bad cholesterol HDLs on the other hand remove excess cholesterol and are protective HDL cholesterol IS good cholesterol... 

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. 

Attempts to isolate GTF from brewer s yeast have resulted in production of very active concentrates, but the substance is too labile to be obtained in the soHd state (136). However, it has been shown that GTF is a Cr(III) complex containing two coordinated nicotinate radicals and other amino acid anions (146). Active preparations containing similar complexes have been synthesi2ed (147). Chromium deficiency may also lead to atherosclerosis and peripheral neuropathy. 

Vascular grafts are tubular devices implanted throughout the body to replace blood vessels which have become obstmcted by plaque, atherosclerosis, or otherwise weakened by an aneurysm. Grafts are used most often in peripheral bypass surgery to restore arterial blood flow in the legs. 

H. Van BeUe, Cholesterol, Bile Acids, and Atherosclerosis, North-HoUand Publishing Co., Amsterdam, the Netherlands, 1965. 

For many years, there has been concern by medical professionals and nutritionists over the effects of dietary sugar on human health. Sucrose has been imphcated as a cause of juvenile hyperactivity, tooth decay, diabetes meUitus, obesity, atherosclerosis, hypoglycemia, and nutrient deficiencies. 

Homocysteine arises from dietary methionine. High levels of homocysteiae (hyperhomocysteinemia) are a risk factor for occlusive vascular diseases including atherosclerosis and thrombosis (81—84). In a controlled study, semm folate concentrations of <9.2 nmol/L were linked with elevated levels of plasma homocysteiae. Elevated homocysteine levels have beea associated also with ischemic stroke (9). The mechanism by which high levels of homocysteine produce vascular damage are, as of yet, aot completely uaderstood. lateractioa of homocysteiae with platelets or eadothehal cells has beea proposed as a possible mechanism. Clinically, homocysteine levels can be lowered by administration of vitamin B, vitamin B 2> foHc acid. 

Despite stmctural similarities, the pharmacological consequences of excesses of these substances are quite different. Due to the interest in the effects of nicotinic acid on atherosclerosis, and in particular its use based on its abiUty to lower semm cholesterol, the toxicity of large doses of nicotinic acid has been evaluated. Eor example, in a study designed to assess its abiUty to lower semm cholesterol, only 28% of the patients remained in the study after receiving a large initial dose of 4 g of nicotinic acid due to intolerance at these large doses (70). 

Homocysteine has been identified as an independent risk factor for atherosclerosis (32) and thus metaboHc control over homocysteine levels has major health implications. 

Reduction in semm Hpids can contribute significantly to prevention of atherosclerosis. In 1985 a consensus report indicating that for every 1% reduction in semm cholesterol there is a 2% reduction in adverse effects of coronary heart disease was issued (145). Recommended semm cholesterol concentration was 200 mg/dL for individuals under 30 years of age, and individuals having concentration 240 mg/dL and LDL-cholesterol over 160 mg/dL should undertake dietary modification and possibly pharmacotherapy (146). Whereas the initial step in reducing semm cholesterol is through reduction of dietary cholesterol intake, a number of dmgs are available that can affect semm Hpid profile (see Fat substitutes). The pathway to cholesterol synthesis is shown in Figure 2. 

Other Cardiovascular Agents Effecting Atherosclerosis. A large amount of clinical data is available concerning semm Upid profiles in patients subjected to dmg therapy for other cardiovascular diseases. Atheroma, for example, may be the underlying cause of hypertension and myocardial infarction. There are on the order of 1.5 million heart attacks pet year in the United States (155). 

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. 

Probucol. Probucol is an antioxidant that is effective in lowering LDL cholesterol. Whereas probucol was known to lower cholesterol after relatively simple clinical trials (160), its mechanism of action as an antioxidant in the treatment of atherosclerosis is quite novel. Probucol has been shown to have the abiUty to produce regression of atherosclerotic lesions in animal models (161). Probucol therefore represents a novel class of pharmaceutical agent for the treatment of atherosclerosis. This effect occurs mechanistically, in part, by preventing oxidation of LDL, a necessary step in foam cell formation. This antioxidant activity has been shown in laboratory experiments and its activity in lowering LDL cholesterol in human studies is well documented (162). 

Thrombolytic Enzymes. Although atherosclerosis and the accompanying vascular wall defects are ultimately responsible for such diseases as acute pulmonary embolism, arterial occlusion, and myocardial infarction, the lack of blood flow caused by a fibrin clot directly results in tissue injury and in the clinical symptoms of these devastating diseases (54). Thrombolytic enzyme therapy removes the fibrin clot by dissolution, and has shown promise in the treatment of a number of thrombo-occlusive diseases (60). 

Thus, it is apparent that soya, some soya products and linseed oil influence blood lipid levels, particularly cholesterol and LDL cholesterol. While the extent of the reduction appears to largely depend on an individual s initial serum cholesterol level, the maximum reductions observed are of the order of 10-15%. For hyperlipidemic individuals this may not be a marked reduction, but such an effect on the general population may well have a beneficial effect on the overall incidence of cardiovascular disease and atherosclerosis. The possibility that non-phytoestrogenic dietary components may contribute to the hypocholes-terolemic properties cannot, however, be discounted. Indeed, certain types of dietary fibre have been shown to have a hypolipidemic effect via their ability to increase faecal excretion rates. 

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. 

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