Atherosclerosis hyperlipidemia

Introduction - This review will present recent developments on the etiology and treatment of atherosclerosis, hyperlipidemia and cholelithiasis. The other major lipid disorder, obesity, has recently been reviewed as to pathogenesis and treatment,1 new efficacy trials and mechanism of action studies on anorectic agents,2 5 and appetite regulation in normal and abnormal states.3 6... 

Diet-Related Risk Factors for Human Atherosclerosis Hyperlipidemia, Hypertension, Hyperglycemia — Current Status. ... 

As described in the previous section, bile acids have evolved over the last years from regulators of bile acid homeostasis to general metabolic integrators. It is therefore not too surprizing that a number of bile acid-activated signaling pathways have become attractive targets for the treatment of gallstones and other metabolic diseases, such as obesity, type 2 diabetes, hyperlipidemia, and atherosclerosis. 

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

Based on the conventional understanding that CAD results from hyperlipidemia, atherosclerosis has been treated with good success by reduction of serum... 

As noted above, obesity is a health problem. It is associated with both elevated mortality and morbidity. More specifically, obesity is a risk factor for cardiovascular disease, including heart attack and stroke, and for high blood pressure (hypertension), diabetes, and hyperlipidemia (elevated levels of lipids in the blood, a risk factor for atherosclerosis and its sequelae), and for cancer. 

Lowering cholesterol levels can arrest or reverse atherosclerosis in all vascular beds and can significantly decrease the morbidity and mortality associated with atherosclerosis. Each 10% reduction in cholesterol levels is associated with an approximately 20% to 30% reduction in the incidence of coronary heart disease. Hyperlipidemia, particularly elevated serum cholesterol and low density lipoprotein (LDL) levels, is a risk factor in the development of atherosclerotic cardiovascular disease. 

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). 

NO also reduces endothelial adhesion of monocytes and leukocytes, key features of the early development of atheromatous plaques. This effect is due to the inhibitory effect of NO on the expression of adhesion molecules on the endothelial surface. In addition, NO may act as an antioxidant, blocking the oxidation of low-density lipoproteins and thus preventing or reducing the formation of foam cells in the vascular wall. Plaque formation is also affected by NO-dependent reduction in endothelial cell permeability to lipoproteins. The importance of eNOS in cardiovascular disease is supported by experiments showing increased atherosclerosis in animals deficient in eNOS by pharmacologic inhibition. Atherosclerosis risk factors, such as smoking, hyperlipidemia, diabetes, and hypertension, are associated with decreased endothelial NO production, and thus enhance atherogenesis. 

The two major clinical sequelae of hyperlipidemias are acute pancreatitis and atherosclerosis. The former occurs in patients with marked hyperlipemia. Control of triglycerides can prevent recurrent attacks of this life-threatening disease. 

The decision to use drug therapy for hyperlipidemia is based on the specific metabolic defect and its potential for causing atherosclerosis or pancreatitis. Suggested regimens for the principal lipoprotein disorders are presented in Table 35-2. 

Monogenic dyslipoproteinemias can generally be grouped into five categories (1) hypertriglyceridemia with an increase in chylomicrons and the clinical sign of pancreatitis, (2) mixed hyperlipidemia with an increase in chylomicron and VLDL remnants and an increased risk of premature atherosclerosis, (3) hypercholesterolemia with an increase in LDL and an increased risk for premature atherosclerosis, (4) hypoalphalipoproteinemia with low HLD and an increased risk for premature atherosclerosis, and (5) hypolipoproteinemia with a decrease in VLDL and LDL, which may lead to neurological disease. 

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.]... 

Harris ID, Evans V, Owen JS. 2006. ApoE gene therapy to treat hyperlipidemia and atherosclerosis. Curr Opin Mol Ther. 8 275-287. 

Giral P, Bruckert E, Jacob N, Chapman MJ, Foglietti MJ, Turpin G. Homocysteine and lipid lowering agents. A comparison between atorvastatin and fenofibrate in patients with mixed hyperlipidemia. Atherosclerosis 2001 154(2) 421-7. 

Hyperlipidemia, an abnormally high concentration of lipids in the bloodstream, is one of the primary causes of cardiovascular disease in industrialized nations. This condition typically causes deposition of fatty plaquelike lesions on the walls of large and mediumsized arteries atherosclerosis), which can lead to throm-... 

Hyperlipidemia can lead to atherosclerosis and subsequent cardiovascular incidents such as thrombosis and infarction. This condition is often treated by a combination of drug therapy and diet and life-style modifications. Pharmacologic interventions are typically targeted toward decreasing the synthesis of harmful (atherogenic) plasma components, including certain lipoproteins (IDL, LDL, VLDL) that are associated with atherosclerotic plaque formation. 

Skullcap is known to have anticonvulsant and sedative properties. Traditionally, it has been used for epilepsy, chorea, hysteria, nervous tension states, and specifically for grand mal. In Chinese herbal medicine, the roots of Scutellaria baicalensis Georgi have been used traditionally as a remedy for inflammation, suppurative dermatitis, allergic diseases, hyperlipidemia, and atherosclerosis. 

Diet is a strong factor in the control of atherosclerosis relating to general vascular disease, coronary heart disease, and stroke. The interrelated disorders in atherosclerosis of hyperinsulinemia, hyperlipidemia, and hypertension are strongly subject to dietary influence. The type of dietary protein, animal vs. plant, appears to be as important as the type of lipid, animal vs. plant, in atherosclerosis. Dietary protein type, with its differing amino acid ratios, appears to be a major secretagogue of insulin. 

Normal coronary arteries can dilate in response to ischemia, increasing delivery of oxygen to the myocardium. This is mediated by nitric oxide, which acts upon smooth muscle cells of the arterial media. This function is impaired by atherogenic lipoproteins in several phenotypes of hyperlipidemia, aggravating ischemic manifestations of atherosclerosis. Reducing levels of atherogenic lipoproteins and inhibition of their oxidation helps restore endothelial function. 

Groenendijk M, De Bruin TW, Dallinga-Thie GM. Two polymorphisms in the apo A-IV gene and familial combined hyperlipidemia. Atherosclerosis. 2001, 158 369-76. 

Yagu, H., Kitamine, T., Osuga, J., Tozawa, R., Chen, Z., et al. (2000) Absence of ACAT-1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia. J. Biol. Chem. 275,21324-21330. 

In lipid metabolism, there is elegant balance in the levels of end-product lipids, and the enzymes and genes involved in their biosynthesis, as well as close cooperation with other metabolisms to maintain homeostasis. When the balance is lost, obesity or hyperlipidemia will develop, leading to a variety of serious diseases including atherosclerosis, hypertension, diabetes, functional depression of certain organs, and so on. Therefore, the control of lipid metabolism by drugs could lead to the prevention or treatment of these diseases. 

Hausmann D, Johnson JA, Sudhir K, et al. Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia correlation with high density lipoproteins, J Am Coll Cardiol I 996 27 1 562-1 570. 

H21. Hazzard, W. R., Wamick, G. R., Utermann, G., Albers, J. J., and Lewis, B., The complex genetics of Type III hyperlipoproteinemia Influence of co-inherited monogenic hyperlipidemia upon the phenotypic expression of apolipoprotein E3 deficiency. In Atherosclerosis V (A. M. Gotto, Jr., L. C. Smith, and B. Allen, eds.), pp. 260-263. Springer-Verlag, Berlin and New York, 1980. 

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