Hypercholesterolemia-atherosclerosis

Again the mechanisms through which this state operates has not been adequately elucidated. Some authors have stated that it abrogated preconditioning,25 however others have shown that it is still present in the hypercholesterolemic rabbit.26 

---

Yamamoto A, Matsuzawa Y, Kishino B, Hayashi R, Hirobe K, Kikkawa T. Effects of probucol on homozygous cases of familial hypercholesterolemia. Atherosclerosis 1983 48 157-166. 

M19. Matsunaga, A., Handa, K., Mori, T., Moryama, K., Hidaka, K., Yuki, M., Sasaki, J., and Arakawa, K., Effects of nieritrol on levels of serum lipids, lipoprotein(a) and fibrinogen in patients with primary hypercholesterolemia. Atherosclerosis [Pg.126]

T4. Tato, F., Keller, C., Schuster, H., Spengel, F., Wolfram, G., and Zollner, N., Relation of lipoprotein(a) to coronary heart disease and duplex sonographic findings of the carotid arteries in heterozygous and familial hypercholesterolemia. Atherosclerosis (Shannon. Irel.) 101, 69-77 (1993). 

Carmena-Ramon RF, Ordovas JM, Ascaso JF, Real J, Priego MA, Carmena R. Influence of genetic variation at the apo A-I gene locus on lipid levels and response to diet in familial hypercholesterolemia. Atherosclerosis. 1998,139 107-113. 

Heinemann, T., Leiss, O., and von Bergmann, K. 1986. Effect of low-dose sitostanol on serum cholesterol in patients with hypercholesterolemia. Atherosclerosis 61, 219-223. 

Yamamoto, A., Sudo, H., and Endo, A. (1980). Therapeutic effects of ML-236B in primary hypercholesterolemia. Atherosclerosis 35 259-266. 

Schwandt, P, Richter, W.O., Weisweiler, P. and Neureuther, G. 1982. Cholestyramine plus pectin in treatment of patients with familial hypercholesterolemia, Atherosclerosis, 44 379-383. 

Brown and Goldstein discovered that FH cells from homozygote donors showed little or no LDL-binding activity. FH cells from heterozygotes possessed about 50% of normal activity. They concluded that mutations in the gene encoding the LDL receptor are the molecular basis for the FH disease. The inability to clear LDL through the normal LDL receptor pathway causes hypercholesterolemia atherosclerosis. 

Small amounts of trans-unsamrated fatty acids are found in ruminant fat (eg, butter fat has 2-7%), where they arise from the action of microorganisms in the rumen, but the main source in the human diet is from partially hydrogenated vegetable oils (eg, margarine). Trans fatty acids compete with essential fatty acids and may exacerbate essential fatty acid deficiency. Moreover, they are strucmrally similar to samrated fatty acids (Chapter 14) and have comparable effects in the promotion of hypercholesterolemia and atherosclerosis (Chapter 26). 

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. 

Familial type III hyperlipoproteinemia (broad beta disease, remnant removal disease, familial dysbetalipoproteinemia) Deficiency in remnant clearance by the liver is due to abnormality in apo E. Patients lack isoforms E3 and E4 and have only E2, which does not react with the E receptor. Increase in chylomicron and VLDL remnants of density < 1.019 (P-VLDL). Causes hypercholesterolemia, xanthomas, and atherosclerosis. 

RUKMINI c, REDDY SASTRY c, MCPEAKP, LYNCH I (2000) Method for treating hypercholesterolemia, hyperlipidemia, and atherosclerosis. US Patent 6,126,943. 

Lipitor (Atorvastatin) Atherosclerosis Dyslipidemia Hypercholesterolemia 3.8 1.3 1997 - UK and US Once daily... 

Erotein whether or not cholesterol was added to the diets C3) ince the publication of this experiment over 45 years ago, there has been a recent resurgence of interest in the area of protein effects on plasma lipids and atherosclerosis. This paper summarizes some of the data generated in our laboratory over the last several years and discusses their significance in relation to hypercholesterolemia and atherosclerosis in other species including humans. 

The standard diet used in our experiments is a semipurified, cholesterol-free preparation that is composed of 25% protein, 40% sucrose, 13% coconut oil, 1% corn oil, 15% cellulose, 5% mineral mix, and 1% vitamin mix. This diet has been shown to induce an endogenous hypercholesterolemia and lead to atherosclerosis in rabbits and monkeys (4, 5). The specific question addressed by our series of investigations is whether the type of dietary protein, when all other dietary components are constant, can influence the development of hyperlipoproteinemia and atherosclerosis. More specifically, we have examined the effects of the individual amino acids, lysine and arginine, and their ratios in the diet on plasma and hepatic lipids as well as the development of arterial plaques. 

Ila i i j i Familial hypercholesterolemia Autosomal dominant (Aa 1/500, AA 1/10 ) Cholesterol LDL High risk of atherosclerosis and coronary artery disease Homozygous condition usually death <20 years Xanthomas of the Achilles tendon Tuberous xanthomas on elbows Xanthelasmas Comeal arcus... 

The answer is D. This patient s tests indicate that he has severe hypercholesterolemia and high blood pressure in conjunction with atherosclerosis. The deaths of several of his family members due to heart disease before age 60 suggest a genetic component, ie, familial hypercholesterolemia. This disease results from mutations that reduce production or interfere with functions of the LDL receptor, which is responsible for uptake of LDL-cholesterol by liver cells. The LDL receptor binds and internalizes LDL-choles-terol, delivers it to early endosomes and then recycles back to the plasma membrane to pick up more ligand. Reduced synthesis of apoproteins needed for LDL assembly would tend to decrease LDL levels in the bloodstream, as would impairment of HMG CoA reductase levels, the rate-limiting step of cholesterol biosynthesis. Reduced uptake of bile salts will also decrease cholesterol levels in the blood. 

Atherosclerosis is a progressive vascular fibroproliferative-inflammatory disease. It is triggered, maintained, and driven by risk factors such as hypercholesterolemia, hyperlipidemia, and hypertonus [28]. The characteristic clinical manifestation of atherosclerosis is the atherosclerotic lesion, developing in the vessel wall (atherosclerotic plaque). 

---