Atherosclerosis Thrombosis

Supplements of 400 Ig/d of folate begun before conception result in a significant reduction in the incidence of neural mbe defects as found in spina bifida. Elevated blood homocysteine is an associated risk factor for atherosclerosis, thrombosis, and hypertension. The condition is due to impaired abihty to form methyl-tetrahydrofolate by methylene-tetrahydrofolate reductase, causing functional folate deficiency and resulting in failure to remethylate homocysteine to methionine. People with the causative abnormal variant of methylene-tetrahydrofolate reductase do not develop hyperhomocysteinemia if they have a relatively high intake of folate, but it is not yet known whether this affects the incidence of cardiovascular disease. 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

Staprans J., et al. (1998). Oxidized cholesterol in the diet accelerates the development of aortic atherosclerosis in cholesterol-fed rabbits. Atherosclerosis, Thrombosis, and Vascular Biology, 18, 977. 

Previously, low fat intakes were traditionally reeommended in the prevention of cardiovascular disease (CVD) as a component of a health promoting diet, without much attention to the quality of fat. However, current dietary guidelines generally put more emphasis on the quality of fat [1-4]. Imbalances in the amounts of individual fatty acids in the diet may have an impact on the occurrence of dyslipidemia, atherosclerosis, thrombosis, hypertension and obesity. Saturated fatty acids (SFA) have shown to be particularly important for development of the above mentioned diseases. However, in spite of an increasing body of new data, the role of individual dietary SFA in metabolic diseases is not fully clarified (Micha 2010). The reaches dietary sources of SFA include fast foods, processed foods, high-fat dairy products, red meats, and pork [1,5]. 

Mensink, R.P. and Katan, M.B. Effects of dietary fatty acids on serum lipids and lipoproteins. A meta analysis of 27 trials. Atherosclerosis Thrombosis 12, 911-919 (1992). 

Vascular conditions these include atherosclerosis, thrombosis, and hypertension and are predominant. 

The pathogenesis of arterial stenosis or occlusion may be secondary to a wide spectrum of etiologic factors including atherosclerosis, thrombosis, embolic events of various etiology, fibromuscular dysplasia, vasculitidies, dissection, trauma, external compression, and vasospastic syndromes. Atherosclerosis is by far the most common cause of arterial stenosis. 

Elevated blood homocysteine is a significant risk factor for atherosclerosis, thrombosis and hypertension, independent of factors such as dietary lipids and plasma lipoproteins (section 7.3.2). About 10-15% of the population, and almost 30% of people with ischaemic heart disease, have an abnormal variant of methylene-tetrahydrofolate reductase (Figure 11.23) that is unstable and loses activity faster than normal. 

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. 

Familial lipoprotein(a) excess Lp(a) consists of 1 mol of LDL attached to 1 mol of apo(a). Apo(a) shows structural homologies to plasminogen. Premature coronary heart disease due to atherosclerosis, plus thrombosis due to inhibition of fibrinolysis. 

HAYEK T, FURHMAN B, VAYA J, ROSENBLAT M, BELINRY P, COLEMAN R, ELIS A, AVIRAM M (1997) Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consiunption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation aggregation, Arteriosclerosis, Thrombosis and Vascular Biology, 17, 2744-52. 

Platelets play a role in each of the mechanisms of normal hemostasis vasoconstriction, formation of the platelet plug, and blood coagulation. However, they are also involved in pathological processes that lead to atherosclerosis and thrombosis (formation of a blood clot within the vascular system). Antiplatelet drugs interfere with platelet function and are used to prevent the development of atherosclerosis and formation of arterial thrombi. 

Various antibody preparations have been developed that facilitate imaging of vascular-related conditions, including myocardial infarction, deep vein thrombosis and atherosclerosis. Anti-myosin monoclonal antibody fragments (Fab) labelled with mIn, for example, have been used for imaging purposes in conjunction with a planar gamma camera. The antibody displays specificity for intracellular cardiac myosin, which is exposed only upon death of heart muscle tissue induced by a myocardial infarction (heart attack). 

Accumulation of homocystine in blood is associated with cardiovascular disease deep vein thrombosis, thromboembolism, and stroke dislocation of the lens (ectopic lens) and mental retardation. Homocystinemia caused by an enzyme deficiency is a rare, but severe, condition in which atherosclerosis in childhood is a prominent finding. These children often have myocardial infarctions before 20 years of age. Ail patients excrete high levels of homocystine in the urine. Treatment includes a diet low in methionine. The two major enzyme deficiencies producing homocystinemia are ... 

Vitamin deficiencies may produce a more mild form of homocystinemia. Mild homocystinemia is associated with increased risk for atherosclerosis, deep vein thrombosis, and stroke. The vitamin deficiencies causing homocystinemia include ... 

Vitamin K antagonists, such as dicoumarol (8.61, a natural product) and warfarin (8.62), are used as anticoagulants in human therapy (thrombosis, atherosclerosis) and as rat poisons that lead to internal bleeding and death in rodents. Heparin, a polysaccharide consisting of 2-0-sulfonated glucuronic acid and 2-N,6-0-disulfonated glucosamine, is also a widely used anticoagulant, but its effect is connected not with Vitamin K but with enzyme inhibition. 

The herbs in this group can be selected as chief and deputies to dissolve congealed blood they can also stimulate blood circulation. They are mainly used to treat the more severe or chronic syndromes of blood stagnation where the blood becomes thicker and blood clots are formed, such as in atherosclerosis, hyperlipemia, thrombosis, endometriosis, adhesions in chronic infection and after surgical operations. 

Platelet-blood vessel interactions are implicated in the development of thrombosis and atherosclerosis [87]. Since Giyglewski and co-workers... 

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