Atherosclerosis Consequences

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). 

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. 

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. 

Apolipoprotein AI (apoAI) is the major apolipoprotein of HDL and plays an important role in the formation of mature HDL and the reverse cholesterol transport. HDL concentrations are largely determined by the rate of synthesis of apoAI in the liver. As a consequence deficiency of apoAI results in an almost complete absence of HDL and in accelerated atherosclerosis. In the promoter of the apoAI... 

Antioxidizability and its control are relevant for various areas in medicine and industry. Atherosclerosis, cardiac infarction, malignant growth, and aging are consequences of uncontrolled oxidation. Currently, oxidizability and antioxidants are also actual problems for alternative and complementary therapies like phyto-, helio-, and aero-ion therapy. 

Familial lipoprotein lipase deficiency is characterized by a massive accumulation of chylomicrons and a corresponding increase in plasma triglycerides or a type I lipoprotein pattern. Presenting manifestations include repeated attacks of pancreatitis and abdominal pain, eruptive cutaneous xanthomatosis, and hepatosplenomegaly beginning in childhood. Symptom severity is proportional to dietary fat intake, and consequently to the elevation of chylomicrons. Accelerated atherosclerosis is not associated with this disease. 

Atherosclerosis, a disease of the vascular wall, is the substrate for the arterial forms of CVD. Atherosclerotic plaques exhibit a focal distribution along the arterial tree as a consequence of local conditions that favor their initiation and progression. Low or reversed shear stress, for example, contributes to plaque development, a process in which the regulation of several genes may be involved (Resnick and Gimbrone 1995). 

These cells, located in the medial layer of the vessel wall, are normally relatively nonproliferative, but they secrete proteins which make up the extracellular matrix of the vessel wall. However, the narrowing of the arteries, a critical, often fatal, consequence of atherosclerosis is due to proliferation of VSMC and their migration into the intimal layer of the vessel wall. 

Atherosclerosis is not itself a disease but it can lead to a poor supply of blood to tissues/organs, which consequently impairs mitochondrial ATP generation and hence can interfere with the function of that tissue. This leads initially to iU health, but can become sufficiently severe to lead to disease and, eventually, to death (see Chapter 22). 

After binding, the LDL-receptor complex is internalized by endocytosis. [Note A deficiency of functional LDL receptors causes a significant elevation in plasma LDL and, therefore, of plasma cholesterol. Patients with such deficiencies have type II hyperlipidemia (familial hypercholesterolemia) and premature atherosclerosis. The thyroid hormone, T3, has a positive effect on the binding of LDL to its receptor. Consequently, hypothyroidism is a common cause of hypercholesterolemia.]... 

People with severe hypertriglyceridemia associated with Type V hyperlipoproteinemia may be at increased risk of hypervitaminosis A, even with moderate degrees of vitamin A supplementation (1199). Long-term vitamin A administration is associated with an increase in serum cholesterol and serum triglyceride concentrations (1200) and consequently might be linked with atherosclerosis (SEDA-8, 345) (1201,1202). 

The clinical manifestations of PAD are associated with reduction in functional capacity and quality of life, but because of the systemic nature of the atherosclerotic process there is a strong association with coronary and carotid artery disease. Consequently, patients with PAD have an increased risk of cardiovascular and cerebrovascular ischemic events [myocardial infarction (Ml), ischemic stroke, and death] compared to the general population (4,5). In addition, these cardiovascular ischemic events are more frequent than ischemic limb events in any lower extremity PAD cohort, whether individuals present without symptoms or with atypical leg pain, classic claudication, or critical limb ischemia (6). Therefore, aggressive treatment of known risk factors for progression of atherosclerosis is warranted. In addition to tobacco cessation, encouragement of daily exercise and use of a low cholesterol, low salt diet, PAD patients should be offered therapies to reduce lipid levels, control blood pressure, control blood glucose in patients with diabetes mellitus, and offer other effective antiatherosclerotic strategies. A recent position paper... 

It is important to note that an elevated and/or altered plasma lipid level is only one of a wide range of risk factors that contribute to the clinical manifestations of cardiovascular disease in humans (Lusis, 2000). Consequently, in some studies, the reduced incidence of atherosclerosis in animals fed CLA was not accompanied by an improvement in the plasma lipid profile during the CLA feeding phase (Wilson et al, 2000). Reasons for these effects are not understood fully. However, atherosclerosis can also be considered as a chronic inflammatory disease (Libby, 2002) and several important anti-inflammatory effects have been associated with the use of RA these include a reduction in the expression of COX-2, PGE2, reduced release of nitric oxide, a decreased production of pro-inflammatory cytokines, and PPARy activation (Urquhart et al, 2002 Yu et al, 2002 Toomey et al, 2003). 

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