Atherosclerosis and

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. 

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). 

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). 

Orford JL, Selwyn AP, Ganz P, et al (2000) The comparative pathobiology of atherosclerosis and restenosis. Am J Cardiol 86(Suppl) 6H-llH... 

Other drugs such as the neuroleptic, haloperidol, inhibit the induction of hsp70 mRNA in rodent neurons (Sharp et al.. 1992). Although this observation needs to be confirmed in the human population, it raises the possibility that an age-dependent defect in the production of HS proteins is exacerbated by a drug which is commonly used in demented elderly patients. The potential for certain pharmacologic agents to inhibit the HS response could increase the risk for untoward effects of atherosclerosis and hypoxia. A similar concern may be raised with certain calcium channel blockers which also have been found to reduce the synthesis of HS proteins in cardiac myocytes (Low-Friedrich and Schoeppe, 1991). 

One major prerequisite for the maintenance of health is that there be optimal dietary intake of a number of chemicals the chief of these are vitamins, certain amino acids, certain fatty acids, various minerals, and water. Because much of the subject matter of both biochemistry and nutrition is concerned with the smdy of various aspects of these chemicals, there is a close relationship between these two sciences. Moreover, more emphasis is being placed on systematic attempts to maintain health and forestall disease, ie, on preventive medicine. Thus, nutritional approaches to—for example—the prevention of atherosclerosis and cancer are receiving increased emphasis. Understanding nutrition depends to a great extent on a knowledge of biochemistry. 

Figure 1-1. Examples ofthe two-way street connecting biochemistry and medicine. Knowledge ofthe biochemical molecules shown in the top part of the diagram has clarified our understanding ofthe diseases shown in the bottom half—and conversely, analyses ofthe diseases shown below have cast light on many areas of biochemistry. Note that sickle cell anemia is a genetic disease and that both atherosclerosis and diabetes mellitus have genetic components.

Famiiiai hyperchoiesteroiemia (type iia) Defective LDL receptors or mutation in ligand region of apo B-100. Elevated LDL levels and hypercholesterolemia, resulting in atherosclerosis and coronary disease. 

CHOPRA M, MCLOONE u L, o neill m, WILLIAMS N and THURNHAM DI (1996) Fruit and vegetable supplementation - effect on ex vivo LDL oxidation in hiunans , in Kumpulainen, J T and Saonen, J T (eds), Natural Antioxidants and Food Quality in Atherosclerosis and Cancer Prevention, Cambridge, Royal Society of Chemistry, 150-55. 

Convincing evidence indicates that ROS generated both endogenously and also in response to diet and lifestyle factors may play a significant role in the etiology of atherosclerosis and CHD. Indeed, free radicals are responsible for LDL oxidation, which is involved in the initiation and promotion of atherosclerosis. Thus, protection from LDL oxidation by antioxidants such as carotenoids may lead to protection against human CHD. 

Some metabolites of curcumin (particularly tetrahydrocurcumin) may also participate in producing the observed effects of curcumin in different models because these metabolites display greater stabilities than the parent curcumin molecule at physiological pH. Recent data show similar modes of action of curcumin metabolites regarding antioxidant enzyme induction and inhibition of multidrug-resistant proteins. " Additional data indicate that curcumin may even act against other types of diseases such as atherosclerosis " " and Alzheimer s disease. " - " ... 

Reed, J., Cranberry flavonoids, atherosclerosis and cardiovascular health, Crit. Rev. Food Sci. Nutr., 42, 301, 2002. 

Cyanidin is the most common anthocyanin in foods. In addition, anthocyanins are stabilized by the formation of complexes with other flavonoids (co-pigmentation). In the United States, the daily anthocyanin consumption is estimated at about 200 mg. Several promising studies have reported that consumption of anthocyanin-rich foods is associated with reductions of the risks of cancers - and atherosclerosis and with preventive effects against age-related neuronal and behavioral declines. These beneficial effects of anthocyanins might be related to their reported biological actions such as modulators of immune response and as antioxidants. Knowledge of anthocyanin bioavailability and metabolism is thus essential to better understand their positive health effects. 

In atherosclerosis and other heart diseases, the role of carotenoids as antioxidants is probable, but for these types of diseases and also for other degenerative diseases such as cancers, non-antioxidant activities constitute other possible prevention mechanisms. These activities are, for example, stimulation of gap junction communications between cells, and the induction of detoxifying enzymes. The... 

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. 

Coronary angiography detects the location and degree of coronary atherosclerosis and is used to evaluate the potential benefit from revascularization procedures. Stenosis of at least 70% of the diameter of at least one of the major epicardial arteries on coronary angiography is indicative of significant IHD. 

The successful outcome in cholesterol management is to reduce cholesterol and triglycerides below the NCEP ATP III goals in an effort to alter the natural course of atherosclerosis and decrease future cardiovascular events. 

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