Coronary artery, atherosclerosis

Atherosclerosis,coronary artery disease PO Initially, 20 mg/day. Maintenance 10-80 mg once daily or in 2 divided doses. Maximum 80 mg/day. 

Increased production of ET-1 has been implicated in a variety of cardiovascular diseases, including hypertension, cardiac hypertrophy, heart failure, atherosclerosis, coronary artery disease, and myocardial infarction. ET-1 also participates in pulmonary diseases, including asthma and pulmonary hypertension, as well as in several renal diseases. 

Halichlorine (1) (Fig. 11.1) is an alkaloid which was isolated from the marine sponge H. okadai Kadota (Kuramoto et ah, 1996). This compound was revealed to be a novel alkaloid containing an azaspiro[4.5]decane skeleton clarified by detailed spectroscopic analyses. The absolute stereostructure was confirmed by many synthetic studies (Arimoto et ah, 1998 Clive et ah, 2005 Liu et ah, 2009 Trauner et ah, 1999). Halichlorine was shown to inhibit the induction of vascular cell adhesion molecule-1 (VCAM-1) in cultured human umbilical vein endothelial cells. Drugs that block the inflammatory stimuli-induced expression of VCAM-1 may be useful for treating atherosclerosis, coronary artery diseases, angina, and noncardiovascular inflammatory diseases (Kock et ah, 1995). We introduce here the recent aspects of the biological and physiological activities of halichlorine. 

The quinolizidine alkaloid halichlorine (203), isolated from the marine sponge Halichondria okadai, inhibits the induction of vascular cell adhesion molecule-1 (VCAM-1) at IC50 7 pg/ml, which may be useful for treating atherosclerosis, coronary artery diseases, angina and noncardiovascular inflammatory diseases [161]. 

Magnetic resonance angiography (MRA) is a method of imaging blood vessels in the presence of certain diseases, such as angiogenesis, tumors, atherosclerosis, coronary arteries [100], myocardium infarction, vascular injury, and blood flow reduction. Blood pool CA enhanced MRA increases the vessel-to-background ratio [101]. Blood pool CAs can be classified into two types, namely, low molecular weight Gd-based CAs and macromolecular CAs. 

A study of 1401 subjects involved measuring plasma homocysteine and measuring the lesions in the carotid artery, one of the arteries in the body that tends to acquire atherosclerotic lesions. The thickness of the lesions were measured by ultrasonography. Plasma folate, vitamin Bg, and vitamin B12 were also measured. A correlation was found between narrowing of the artery and homocysteine levels at above 15 xM homocysteine. A correlation with narrowing of the artery was also found with folate levels below 2.5 ng/ml, and with vitamin Bg levels below 30 nM (Selhub et al, 1995). A study of 231 normal subjects and 304 patients with atherosclerosis (coronary artery under 30% normal diameter) revealed a striking correlation between plasma homocysteine of 12 pM, or greater, and atherosclerosis (Robinson et al, 1995). These studies help define an upper limit of acceptable plasma homocysteine levels. 

An increase in serum lipids is believed to contribute to or cause atherosclerosis, a disease characterized by deposits of fatty plaques on the inner walls of arteries. These deposits result in a narrowing of the lumen (inside diameter) of the artery and a decrease in blood supply to the area served by the artery. When these fatty deposits occur in the coronary arteries, the patient experiences coronary artery disease. Lowering blood cholesterol levels can arrest or reverse atherosclerosis in the vessels and can significantly decrease the incidence of heart disease. 

Factors that predispose an individual to IHD are listed in Table 4—2. Hypertension, diabetes, dyslipidemia, and cigarette smoking are associated with endothelial dysfunction and potentiate atherosclerosis of the coronary arteries. The risk for IHD increases two-fold for every 20 mm Hg increment in systolic blood pressure and up to eight-fold in the presence of diabetes.5,6 Physical inactivity and obesity independently increase the risk for IHD, in addition to predisposing individuals to other cardiovascular risk factors (e.g., hypertension, dyslipidemia, and diabetes). 

The basic biology of chemokines and their receptors is well covered in Chapters 2 and 3 of this book, and we will focus hereafter upon the roles of individual chemokines and receptors in atherosclerosis. The largest amount of data on the roles of chemokines in cardiovascular disease (C VD) has been obtained from in vitro studies and murine models, which will be discussed in detail. In man, genetic polymorphisms in chemokine and chemokine-receptor genes have pointed to an important role for specific chemokines in various atherosclerotic diseases including coronary artery disease and carotid artery occlusive disease. For properties see Table 1. 

Wong BW, Wong D, McManus BM. Characterization of fractalkine (CX3CL1) and CX3CR1 in human coronary arteries with native atherosclerosis, diabetes mellitus, and transplant vascular disease. Cardiovasc Pathol 2002 ll(6) 332-338. 

Murr C, Winklhofer-Roob BM, Schroecksnadel K, Maritschnegg M, Mangge H, Bohm BO, Winkelmann BR, Marz M and Fuchs D. 2009. Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis. In press. 

Iron-stimulated free radical-mediated processes are not limited to the promotion of peroxidative reactions. For example, Pratico et al. [188] demonstrated that erythrocytes are able to modulate platelet reactivity in response to collagen via the release of free iron, which supposedly catalyzes hydroxyl radical formation by the Fenton reaction. This process resulted in an irreversible blood aggregation and could be relevant to the stimulation by iron overload of atherosclerosis and coronary artery disease. 

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

The formation of atherosclerotic plaques is the underlying cause of coronary artery disease (CAD) and ACS in most patients. Endothelial dysfunction leads to the formation of fatty streaks in the coronary arteries and eventually to atherosclerotic plaques. Factors responsible for development of atherosclerosis include hypertension, age, male gender, tobacco use, diabetes mellitus, obesity, and dyslipidemia. 

Adams MR, Kaplan JR, Manuck SB, Koritnik DR, Parks JS, Wolfe MS, Clarkson TB (1990) Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariec-tomized monkeys. Lack of an effect of added progesterone. Arteriosclerosis 10 1051— 1057... 

Clarkson TB, Anthony MS, Jerome CP (1998) Lack of effect of raloxifene on coronary artery atherosclerosis of postmenopausal monkeys. J Clin Endocrinol Metab 83 721-726... 

A3. Abe, A., Noma, A., Lee, Y. J., and Yamaguchi, H., Studies on apolipoprotein(a) phenotypes. Part 2. Phenotype frequencies and Lp(a) concentrations in different phenotypes in patients with angiographically defined coronary artery diseases. Atherosclerosis (Shannon. Irel.) 96, 9-15 (1992). 

It prevents oxidation of IDL partides. Oxidized LDLs are strongly associated with atherosclerosis and coronary artery disease. 

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... 

This is a dominant genetic disease affecting 1/500 (heterozygous) individuals in the United States. It is characterized by elevated LDL cholesterol and increased risk for atherosclerosis and coronary artery disease. Cholesterol deposits may be seen as ... 

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