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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological studies indicate that there are biological interrelationships between blood pressure and blood lipids that may influence the mechanisms whereby hypertension is associated with an increased risk of coronary artery disease. Serotonin (5-HT) and thromboxane A2, which are released from aggregating platelets, mediate platelet-induced vasoconstriction, which itself significantly contributes to coronary artery constriction in vivo. Platelet aggregatory response to serotonin is modulated by disparate effects of lipoprotein fractions. This corresponds to the recognized differences in degree of atherogenicity of low- (LDL) and high-density lipoprotein (HDL). Amplification of serotonin-induced platelet aggregation by LDL and its inhibition by HDL support the hypothesis that 5-HT-mediated effects represent a mechanism clinically relevant to both chronic progression of atherosclerosis (particularly at sites of vascular injury and atherosclerotic plaques) and acute thrombotic events. Calcium antagonists differ in their platelet-inhibition potency, including their effects on platelet response to 5-HT and LDL. Verapamil and isradipine inhibit platelet aggregation induced by 5-HT at therapeutic concentrations. Isradipine also inhibits the amplifying effect of LDL on 5-HT-induced aggregation. These platelet effects of calcium antagonists appear to be neither group- nor class-specific but, rather, drug-specific.
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PMID:Platelet activation by low-density lipoprotein and serotonin: effects of calcium antagonists. 137 30

Recent multicentre studies evaluating the therapeutic value of calcium antagonists in reducing the incidence of cardiovascular complications after myocardial infarction (secondary prevention) and in retarding the development of atherosclerosis in coronary artery disease (tertiary protection) are reviewed. The prognosis of patients after acute myocardial infarction can be improved not only by interventional measures such as aortocoronary bypass surgery or percutaneous transluminal catheter angioplasty, but also by various drugs. Numerous studies have shown that beta-blockers and platelet aggregation inhibitors can reduce mortality and reinfarction rates. Calcium antagonists in secondary prevention trials after acute myocardial infarction, however, have produced variable results. Whereas the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) [Israeli SPRINT Study Group 1988] with nifedipine showed no beneficial effect of the drug, studies with verapamil in the Danish Verapamil Infarction Trial II (DAVIT II) [Danish Study Group on Verapamil in Myocardial Infarction 1990] and diltiazem in the Multicentre Diltiazem Postinfarction Trial (MDPIT) [Multicenter Diltiazem Postinfarction Trial Research Group 1988] as secondary prevention have demonstrated improvements in survival and cardiovascular complications, but these improvements were restricted to patients without heart failure. In view of the ability of calcium antagonists to reduce atheroma progression in coronary artery disease in animal models, the antiatherosclerotic effects of these agents in clinical studies have generally been disappointing. In the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT) [Lichtlen et al. 1990], however, nifedipine treatment was associated with a 28% reduction in new lesion development, but did not affect the development of severe lesions. Similar results have been obtained with nicardipine.
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PMID:Secondary and tertiary prevention with calcium antagonists in coronary artery disease. 137 87

Factors that can influence cardiovascular growth are becoming increasingly important for our understanding of such complex diseases as cardiac hypertrophy, coronary artery disease, atherosclerosis, and hypertension. Several proto-oncogenes were found to be involved in the regulation of abnormal cell growth in cardiovascular disease. It is also evident that some peptide hormones, which are well known to be involved in blood pressure control, may play a role as growth modulators. Angiotensin II is one such peptide. It elevates blood pressure through its direct vasoconstrictor, sympathomimetic, and (through release of aldosterone) sodium-retaining activity but also appears to have mitogenic actions. Interestingly, all components of the renin-angiotensin system were found locally in cardiovascular tissues. The question remains whether angiotensin can act directly as a growth factor or whether it does so indirectly by influencing or modulating cell growth factors. A better understanding of the renin-angiotensin system as a direct or indirect mediator for cardiovascular hypertrophy would offer new and interesting insights into the pathophysiology of hypertension and possibly novel options for the treatment of cardiovascular disease.
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PMID:The molecular basis of cardiovascular hypertrophy: the role of the renin-angiotensin system. 138 95

This study was undertaken to study the effects of hyperlipidemia and hypertension on the coronary circulation and on the myocardium of Watanabe heritable hyperlipidemic (WHHL) rabbits. Surgery to induce hypertension by the one-kidney, one-clip technique was performed on the WHHL rabbits at 3 months of age. At 3 and 6 months after surgery, the right and left coronary arteries and the left ventricle and posterior papillary muscle from normotensive and hypertensive animals were assessed. Atherosclerotic involvement was found at the coronary origin in 94% of the arteries evaluated. Lesions were usually confined to the proximal 1-2 mm of the coronary artery. The prevalence of coronary atherosclerosis in the WHHL rabbit was found to be higher than previously reported in rabbits of the same age. Hypertension-induced muscular and vascular changes such as left ventricular hypertrophy, medial thickening of the arteries, and hyaline arteriolosclerosis were found in most of the hypertensive animals. These changes were rarely seen in the normotensive rabbits. Characteristics of ischemia and cell injury such as eosinophilic fibers, fiber vacuolization, and contraction band necrosis were found more often in hypertensive than in normotensive WHHL rabbits. Confluent areas of severe necrosis indicative of myocardial infarction were not found; myocardial damage was diffuse and involved individual cells and small microscopic areas. This model may be valuable in further studies of coronary artery disease and myocardial injury that result from the combination of hypercholesterolemia and hypertension.
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PMID:Effects of hypertension and hyperlipidemia on the myocardium and coronary vasculature of the WHHL rabbit. 138 26

Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by a deficiency in the receptor that clears low density lipoprotein (LDL) from the serum (reviewed in Ref. 1 and 2). Patients with one abnormal LDL receptor allele have moderate elevations in plasma LDL and suffer premature coronary artery disease (CAD). Approximately 5% of all patients under 45 who have had a myocardial infarction carry this trait. Patients with two abnormal LDL receptor genes (homozygous deficient patients) have severe hypercholesterolemia and life-threatening coronary artery disease in childhood. Strategies for treating patients with FH are directed at lowering the plasma level of LDL. In heterozygotes, this is accomplished through the administration of drugs that stimulate the expression of LDL receptor from the normal allele (2). This therapeutic approach is not effective in the treatment of homozygous deficient patients, especially those that retain less than 2% of residual LDL receptor activity. Partial amelioration of hyperlipidemia has been achieved in some homozygous deficient patients by diverting the portal circulation through a portacaval anastomosis (3) and by chronic plasmapheresis therapy (4). A more direct approach has been to correct the deficiency of hepatic LDL receptor by transplanting a liver that expresses normal levels of LDL receptor. Three patients that survived this procedure normalized their serum LDL-cholesterol (5-9). We have used an authentic animal model for FH, the Watanabe Heritable Hyperlipidemic rabbit (WHHL), to develop gene therapies for the homozygous form of FH (10-13). The WHHL rabbit has a mutation in its LDL receptor gene which renders the receptor completely dysfunctional (12) leading to severe hypercholesterolemia, diffuse atherosclerosis, and premature death. The potential efficacy of gene therapy for FH is supported by a series of studies we have performed in the WHHL rabbit in which we have achieved metabolic improvement (14-18). Liver tissue was removed from WHHL rabbits and used to isolate hepatocytes and establish primary cultures. A functional rabbit LDL receptor gene was transduced into a high proportion of hepatocytes using recombinant retroviruses, and the genetically corrected cells were transplanted into the animal from which they were derived. Transplantation of the genetically corrected, autologous hepatocytes was associated with a 30-40% decrease in serum cholesterol that persisted for the duration of the experiment (4 months, Ref. 18). Recombinant derived LDL receptor RNA was detected in liver for at least 6 months. There was no apparent immunological response to the recombinant derived LDL receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ex vivo gene therapy of familial hypercholesterolemia. 139 Oct 38

In the last 15 years, intense interest has focused on various interventional pharmacologic and mechanical forms of therapy for the treatment of atherosclerosis coronary artery disease. Many techniques and devices (dilating balloons, perfusion catheters, thermal probes and balloons, lasers, atherectomy devices, stents, intravascular ultrasound) have been used or are under study for future use. Many of these techniques and devices require an understanding of histologic and pathologic features of the coronary arteries and diseases which affect them. This article reviews selective areas of anatomy, histology, and pathology relevant to the use of various new interventional techniques. Part IV of this review will focus on congenital coronary artery anomalies, myocardial bridges, coronary aneurysm, emboli, and dissection and clinical implications regarding echocardiographic imaging techniques.
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PMID:Anatomy, histology, and pathology of coronary arteries: a review relevant to new interventional and imaging techniques--Part IV. 139 3

The aims of this study were to evaluate plasma lipid, apoprotein and Lp(a) levels in patients with severe coronary atherosclerosis undergoing aorto-coronary bypass surgery (BP) and to relate these parameters to the involvement of one or more vessels. Seventy-seven male patients and 77 cardiovascular disease-free controls, matched for sex, age and body weight were studied. Higher triglyceride and apo B levels with lower HDL-cholesterol and apo A-I levels were found in BP patients in comparison with the controls. Lp(a) levels were slightly, but not significantly, increased. Moreover BP patients presented a significantly higher prevalence of HDL-cholesterol levels below 35 mg dl-1 (49.3% vs 22.1%) and Lp(a) levels above 70 mg dl-1 (10.4% vs 1.3%) than the controls. When patients were divided according to the number of coronary vessels involved (one, two or three), no significant difference was found, with a trend to increase in Lp(a) mean levels and in prevalence of Lp(a) levels above 30 and 70 mg dl-1 in more severely diseased patients. These results suggest that patients with severe coronary artery disease undergoing aorto-coronary bypass surgery show low HDL-cholesterol levels with high triglyceride levels. Moreover Lp(a) levels above 70 mg dl-1 are highly associated with severe coronary vessel stenosis.
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PMID:Lp(a) levels in patients undergoing aorto-coronary bypass surgery. 139 16

Carbon disulfide (CS2) is toxic to the heart and arteries; chronic exposure can result in accelerated atherosclerosis and coronary artery disease in humans and animals. Exposure to CS2 was investigated in normal volunteers working in New York City, using a new and highly sensitive assay. Volatile organic compounds in breath and air were captured in adsorbent traps containing graphitized carbon and molecular sieve, then thermally desorbed, concentrated by two-stage cryofocusing, and assayed for CS2 by gas chromatography/mass spectroscopy. Breath CS2 assays were performed in 42 normal volunteers, as well as in room air and in outdoor air collected at sites in and around New York City. The assay was linear, reproducible, and sensitive to picomolar (10(-12) mol/l) quantities. CS2 was detected in all samples of breath and indoor and outdoor air (mean concentrations were 5.25 pmol/l, SD = 3.89 in breath, 8.26 pmol/l in indoor air, and 3.92 pmol/l in outdoor air) (NS). The alveolar CS2 gradient (alveolar-inspired CS2) ranged from -20.0 to 8.0 nmol/l, separating subjects into either "excreters" or "retainers" of CS2. In view of the known toxicity of CS2, atmospheric pollution with CS2 merits attention as a possible new risk factor for the development of accelerated atherosclerosis and coronary artery disease.
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PMID:Detection of carbon disulfide in breath and air: a possible new risk factor for coronary artery disease. 139 21

The development of the nephrotic syndrome is associated with a lipid profile characterized by increased total and low density lipoprotein cholesterol. Although total high density lipoprotein (HDL) values may be in the normal range, there is frequently abnormalities of HDL subclasses, with reduction of the mature HDL2 subfraction. While these lipid changes may be considered a risk for atherosclerosis, they revert to normal with remission of the nephrotic syndrome. However, with chronic nephrotic range proteinuria, these abnormalities persist and may also be associated with increased levels of lipoprotein (a), increased levels of very light density lipoprotein and further reductions in HDL. These factors could all contribute to greater risk for atherosclerosis. Although coronary artery disease is frequently seen in patients with end-stage renal disease, and many uncontrolled studies in patients with chronic nephrotic syndrome have suggested an increased prevalence of cardiovascular disease, no prospective studies to evaluate relationship between lipid abnormalities and cardiac disease have been performed in patients with the nephrotic syndrome. Recent experimental data have also suggested a relationship between hyperlipidemia and progressive renal injury. Unfortunately, human epidemiological data are incomplete in correlating lipid changes with renal disease in patients with chronic nephrotic syndrome. No therapeutic trials have tested whether or not pharmacologic interventions will benefit either the cardiac or renal disease that ensues in patients with chronic persistent nephrotic syndrome. Thus, considerably more data are needed to help clarify this important area.
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PMID:Is the aggressive management of hyperlipidemia in nephrotic syndrome mandatory? 140 64

The renin-angiotensin system (RAS) plays a major role in the control of blood pressure and cardiovascular homeostasis and is involved in the pathogenesis of a number of cardiovascular disorders. The efficacy of angiotensin-converting enzyme (ACE) inhibitors in the treatment of hypertension and congestive heart failure has led to the widespread clinical use of ACE inhibitors in primary or secondary prevention of heart disease. The demonstration of the expression of the components of the RAS in several extrarenal tissues, as well as local generation of angiotensin II, has confirmed the existence of a tissue RAS that may serve organ-specific functions and act independently from the plasma RAS. The concept of paracrine/autocrine functions of the local RAS has changed our understanding of the functions of the RAS and suggests that tissue ACE inhibition may be of greater importance than inhibition of circulating ACE in the treatment of congestive heart failure and other cardiovascular disorders. Whereas the circulating endocrine RAS appears to be responsible for mediation of acute effects, the tissue RAS seems to be involved in more chronic situations, such as secondary structural changes of the cardiovascular system, and therefore could contribute to the pathogenesis of hypertension as well as other cardiovascular disorders, such as cardiac hypertrophy, coronary artery disease, and atherosclerosis. Several experimental and clinical findings suggest that reversal of cardiovascular structural changes secondary to cardiovascular disease and enhancement of renal sodium excretion by ACE inhibitors are important long-term antihypertensive actions possibly mediated by inhibition of the tissue RAS.
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PMID:Effects of angiotensin-converting enzyme inhibitors on tissue renin-angiotensin systems. 141 88


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