Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between vascular angiotensin-converting enzyme (ACE) activity in the aorta and atherosclerotic lesions was investigated in rabbits fed two atherogenic diets, 0.5 and 1.5% cholesterol, for 17 wk. Tissue ACE activity was assessed by the cleavage rate of hippuric acid from a synthetic substrate. Total cholesterol, triglycerides, and phospholipids in the serum were significantly increased by the diet. Vascular ACE activity in the femoral artery, abdominal aorta, and aortic arch was significantly increased (2-5 times) by the atherogenic diet in a high-cholesterol-related manner compared with the rabbits fed a normal diet. The increase was associated with vascular heterogeneity of regions. There was a significant correlation between plaque area and vascular ACE activity in the aortic arch isolated from rabbits fed the higher (1.5%)-cholesterol diet. Contractile responses of the femoral artery to angiotensin I and II in the atherogenic diet-fed rabbits did not differ from those in animals fed the normal diet. It is conceivable that increased ACE in the vascular walls is involved in hyperlipidemia-induced atherogenesis, presumably through production of growth or stimulating factor(s) contributing to plaque formation.
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PMID:Increased activity of vascular ACE related to atherosclerotic lesions in hyperlipidemic rabbits. 885 42

In this review, the role of the macrophage in the pathophysiology of coronary artery disease (CAD) is examined. The central interaction of macrophage, endothelial cell and smooth muscle cell in the context of hyperlipidemia is considered. The macrophage appears to be at the beginning of a chain of events that starts with elevated low density lipoprotein (LDL). Stress, particularly in those with a core hostility, may be associated not only with higher catecholamine levels but also with higher serum lipid levels. These lipids will in turn be processed to oxidized LDL by macrophage and endothelial cells. Oxidized LDL molecules will contribute to atherosclerotic plaquing. A side effect of such plaque formation may be a diminished vasodilatory response to the nitric oxide (NO) produced by macrophages and endothelium. Indeed, paradoxical vasoconstriction occurs in atherosclerosis in response to neurotransmitters such as serotonin and acetylcholine, which under normal circumstances cause vasodilation. There also is evidence that both macrophages and endothelial cells can regulate NO production through a specific mu 3 morphine receptor, an effect that can be blocked by naloxone. The clinical effectiveness of morphine and nitroglycerin in CAD patients may relate to these mechanisms. More research will be needed to elucidate the neuroimmunologic basis for atherosclerosis with prospects for better treatment and management in future.
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PMID:Neuroimmunologic implications in coronary artery disease. 887 69

Until the mid 1980s, secondary prevention of coronary atherosclerosis focused primarily on early ambulation, exercise training, and a 'prudent' diet. These regimens generally resulted in improved functional capacity, reduced myocardial demands at submaximal workrates, and modest decreases in cardiovascular mortality. However, reinfarction rates and the course of atherosclerotic heart disease remained largely unchanged with traditional treatment or usual care. Contemporary studies now suggest that multifactorial risk factor modification, and especially more intensive measures to control hyperlipidaemia with diet, drugs, and exercise, may slow, halt, and even reverse the progression of atherosclerotic coronary artery disease. Added benefits include a reduction in anginal symptoms, decreases in exercise-induced myocardial ischaemia, fewer recurrent cardiac events, and a diminished need for coronary revascularisation procedures. Several mechanisms may contribute to these improved clinical outcomes, including partial (albeit small) anatomic regression of coronary artery stenoses, a reduced incidence of plaque rupture, and improved coronary artery vasomotor function. These findings suggest a new paradigm in the treatment of patients with coronary artery disease.
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PMID:Delayed progression or regression of coronary atherosclerosis with intensive risk factor modification. Effects of diet, drugs, and exercise. 892 48

The association between plasma fibrinogen and the presence of carotid, femoral, and aortic plaque (high-resolution B-mode ultrasonography) and coronary calcium deposit (ultrafast computed tomography scanner) was determined in 693 hypercholesterolemic, never-treated men free of previous or current clinical symptoms of cardiovascular disease. The number of subjects with extracoronary disease sites and coronary calcification deposits was significantly higher in the upper than in the lower tertile of fibrinogen. Plasma fibrinogen increased according to the number of diseased sites. The odds ratio of the upper to lower fibrinogen tertile for the presence of arterial lesions was 2.6 (1.7 to 4) for carotid, 2.2 (1.5 to 3.2) for aorta, 2.2 (1.5 to 3.1) for femoral, 1.8 (1.3 to 2.6) for coronary, and 3.6 (2.3 to 6.1) for one of four diseased sites. Adjustment for age, total cholesterol, HDL cholesterol, triglycerides, current smoking, and systolic pressure slightly reduced the association between fibrinogen and atherosclerosis. A synergistic effect between fibrinogen and total cholesterol/ HDL cholesterol (TC/HDL) ratio seemed to be operating on atherosclerosis, because nearly all of the individuals (98%) had a diseased site when fibrinogen and TC/HDL tertiles were the highest. This result suggests that fibrinogen is involved in the subclinical phase of extracoronary and coronary atherosclerosis and may potentiate the atherogenic effect of hyperlipidemia.
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PMID:Fibrinogen and its relations to subclinical extracoronary and coronary atherosclerosis in hypercholesterolemic men. 901 36

Most of the indications for cardiovascular operation and many of its complications are in large part due to advanced atherosclerosis. The pathogenesis of atherosclerosis involves inflammatory infiltration of the vessel wall, cellular proliferation, fibrous plaque formation, and ultimately plaque rupture and occlusive thrombosis. Many of these events are linked, at least initially, to chronic injury of the vascular endothelium. Endothelial cell injury from hypertension, diabetes mellitus, hyperlipidemia, fluctuating shear stress, smoking, or transplant rejection disrupts normal endothelial cell function. This results in the loss of the constitutive protective mechanisms and an increase in inflammatory, procoagulant, vasoactive, and fibroproliferative responses to injury. These changes promote vasospasm, intimal proliferation, and thrombus formation, all of which play a significant role in the initiation, progression, and clinical manifestations of atherosclerosis. Understanding the role of the chronically injured endothelium and its interactions with circulating immune cells and the underlying smooth muscle cells may lead to novel therapeutic interventions for the prevention and treatment of atherosclerosis.
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PMID:Endothelial cell injury in cardiovascular surgery: atherosclerosis. 906 32

Atherosclerosis and its consequences account for most of the morbidity and mortality in Western countries. It is a disease of the intima and primarily involves four cell types, i.e., endothelial and vascular smooth muscle cells, monocytes and platelets. In recent years, knowledge on the cellular and molecular mechanisms of these cells and their alterations by cardiovascular risk factors and in atherosclerosis has greatly expanded. In particular, it has become clear that endothelial cells play a crucial role in the regulation of platelet function, coagulation, and vascular tone and structure. Interestingly, endothelial dysfunction occurs early, particularly if cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes are present. This could lead to adhesion of circulating platelets and monocytes and increased accumulation of lipids in the intima, as well as increased contraction, migration and proliferation of vascular smooth muscle cells. One of the enzymes with a key role in vascular homeostasis is angiotensin I converting enzyme (ACE). ACE is located on the endothelial cell membrane and is responsible for the conversion of angiotensin I into angiotensin II, as well as for the breakdown of bradykinin. While the antihypertensive effect of ACE inhibitors probably contributes to their antiatherogenic effects, other mechanisms are likely to be of greater importance. These direct antiatherogenic effects attributable to ACE inhibition are related to their vasculoprotective properties, including antiproliferative and antimitogenic activity, effects on endothelial function, protection against plaque rupture, antithrombotic effects, and possible antioxidant properties. There is overwhelming evidence to demonstrate the beneficial effects of long-term ACE inhibitor treatment in heart failure, acutely for suspected myocardial infarction (MI), and following MI in patients with left ventricular dysfunction. Hypercholesterolemia is a health risk, and epidemiological studies have shown a line between total cholesterol levels and the risk of cardiac events. Studies have shown that lowering the levels of total and low-density lipoprotein cholesterol using HMG-CoA reductase inhibitors can result in a decrease in cardiac morbidity and mortality. Angiographic studies of coronary arteries have demonstrated a disparity between the decrease in cardiac events and the extent of regression of coronary artery lesions. Mechanisms other than the regression of coronary stenosis may therefore be important in the beneficial effect of cholesterol lowering. It may be of major importance that lipid-lowering therapy is associated with improved endothelial function and decreased platelet activity. Thus, both ACE inhibitors and HMG-CoA reductase inhibitors have vasculoprotective properties which may explain their beneficial effects on cardiovascular morbidity and mortality.
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PMID:[Pharmacotherapy of arteriosclerosis and its complications. Effect of ACE inhibitors and HMG-CoA-reductase inhibitors]. 919 90

To assess the prevalence of extracranial carotid artery atherosclerosis and its relation to principal cardiovascular risk factors in Chinese elderly patients, 100 cases aged from 54 to 94 were investigated with B-mode ultrasonography. Arterial intima-media thickening, plaque, mild stenosis (defined as a plaque that obstructed > 20% of the lumen diameter), and clinically significant stenosis (> 50% in cross-sectional area) were found in 79, 49, 40 and 3 patients, respectively. There was no significant correlation between carotid atherosclerosis and coronary heart disease, cerebral infarction, hypertension, hyperlipidemia or diabetes. In contrast, the prevalence of carotid atherosclerosis was increased with age (P < 0.05), so did the severity. Thus, age is a major risk factor for carotid atherosclerosis in the elderly.
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PMID:[The prevalence and risk factors of carotid atherosclerosis in elderly patients]. 927 42

Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.
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PMID:Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity, and resistance to activated protein C. 943 45

We report a 62-year-old man who developed coma and died in a fulminant course. The patient was well until May 1, 1996 when he noted chillness, tenderness in his shoulders, and he went to bed without having his lunch and dinner. In the early morning of May 2, his families found him unresponsive and snoring; he was brought into the ER of our hospital. He had histories of hypertension, gout, and hyperlipidemia since 42 years of the age. On admission, his blood pressure was 120/70, heart rate 102 and regular, and body temperature 36.3 degrees C. His respiration was regular and he was not cyanotic. Low pitch rhonchi was heard in his right lower lung field. Otherwise general physical examination was unremarkable. Neurologic examination revealed that he was somnolent and he was only able to respond to simple questions such as opening eyes and grasping the examiner's hand, but he was unable to respond verbally. The optic discs were flat; the right pupil was slightly larger than the left, but both reacted to light. He showed ptosis on the left side, conjugate deviation of eyes to the left, and right facial paresis. The oculocephalic response and the corneal reflex were present. His right extremities were paralyzed and did not respond to pain Deep tendon reflexes were exaggerated on the right side and the plantar response was extensor on the right. No meningeal signs were present. Laboratory examination revealed the following abnormalities; WBC 18,400/ml, GOT 131 IU/l GPT 50 IU/l, CK616 IU/l, BUN 30 mg/dl, Cr 2.1 mg/ dl, glucose 339 mg/dl, and CRP 27.4 mg/dl. ECG showed sinus tachycardia and ST elevation in II, III and a VF leads and abnormal q waves in I, V5, and V6 leads. Chest X-ray revealed cardiac enlargement but the lung fields were clear. Cranial CT scan revealed low density areas in the left middle cerebral and left posterior cerebral artery territories. The patient was treated with intravenous glycerol infusion and other supportive measures. At 2: 10 AM on May 3, he developed sudden hypotension and cardiopulmonary arrest. He was pronounced dead at 3:45 AM. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had acute myocardial infarction involving the inferior and the true posterior walls and left internal carotid embolism from a mural thrombus. Post mortem examination revealed occlusion of the circumflex branch of the left coronary artery due to atherom plaque rupture and myocardial infarction involving the posterior and the lateral wall with a rupture in the postero-lateral wall. Marked atheromatous changes were seen in the left internal carotid, the middle cerebral and the basilar arteries; the left internal carotid and the middle cerebral arteries were almost occluded by thrombi and blood coagulate. The territories of the left middle cerebral and the occipital arteries were infarcted; but the left thalamic area was spared. The neuropathologist concluded that the infarction was thrombotic origin not an embolic one as the atherosclerotic changes were severe. Cardiac rupture appeared to be the cause of terminal sudden hypotension and cardiopulmonary arrest. It appears likely that a vegetation which had been attached to the aortic valve induced thromboembolic occlusion of the left internal carotid artery which had already been markedly sclerotic by atherosclerosis. It is also possible that the vegetations in the aortic valve came from mural thrombi at the site of acute myocardial infarction, as no bacteria were found in those vegetations.
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PMID:[A 62-year-old man with an acute onset of consciousness disturbances]. 945 48

It is well established that elevated circulating concentrations of cholesterol-rich, low-density lipoproteins (LDL) represent a major risk factor for the premature development of coronary artery disease. Only recently, however, has attention been drawn to the relationship between the qualitative features of plasma LDL particles and cardiovascular risk, particularly in view of the frequent occurrence of increased levels of dense, small LDL in coronary artery disease patients. Combined hyperlipidaemia, a frequent form of dyslipidaemia which is associated with premature atherosclerosis, is characterized by elevated plasma concentrations of both triglyceride-rich, very-low-density lipoproteins (VLDL) and LDL. In combined hyperlipidaemia patients, small, dense LDL (d 1.04-1.06 g.ml-1) predominate over the light (d 1.02-1.03 g.ml-1) and intermediate (d 1.03-1.04 g.ml-1) LDL subpopulations. Dense LDL are highly atherogenic as a result of their low binding affinity for the LDL receptor, their prolonged plasma half-life and low resistance to oxidative stress. Biological modification of dense LDL is potentiated as a result of retention in the arterial intima upon binding to extracellular matrix components and exposure to oxidative stress, leading to uptake by macrophages with subsequent foam cell formation. Such cholesterol-loaded, macrophage foam cells are active secretory cells, and exert multiple proinflammatory, proatherogenic and prothrombogenic effects during the initiation and progression of atherosclerotic plaques. Indeed, the secretory products of foam cells play a key role in the fragilization of lipid-rich plaques, leading ultimately to plaque rupture and the associated thrombotic complications. As the pharmacological modulation of dense LDL levels is of special interest, representing a new therapeutic approach in the treatment of atherogenic dyslipidaemia, we probed the biological mechanisms which underlie formation of dense LDL particles in combined hyperlipidaemia patients with a fibrate derivate, fenofibrate. Drug treatment (micronized fenofibrate, 200 mg.day-1 for 8 weeks) induced significant reductions in the plasma concentrations of VLDL (-37%; P < 0.005), and of dense LDL (-21.5%; P < 0.05), with simultaneous increase in HDL-cholesterol (+19%; P < 0.0001). An endogenous assay of cholesteryl ester transfer from cardioprotective HDL to atherogenic, apolipoprotein B-containing lipoproteins (VLDL and LDL) revealed marked reduction (-38%) in cholesterol ester transfer from HDL to VLDL upon fenofibrate treatment, whereas no modification in the low rate of cholesteryl ester transfer between HDL and LDL was detected. Simultaneously, however, the LDL profile in combined hyperlipidaemia patients, which is characterized by a predominance of small, dense LDL, was shifted towards the LDL subpopulation of intermediate density and larger size. Particles of the intermediate LDL subclass are avidly bound and degraded by the cellular LDL receptor which represents the major, non-atherogenic pathway for catabolism of LDL-cholesterol. Our findings indicate that the overall mechanism of the fenofibrate-induced modulation of the atherogenic dense LDL profile in combined hyperlipidaemia involves reduction in cholesteryl ester transfer from HDL to VLDL, together with normalization of the intravascular transformation of hepatic VLDL to receptor-active LDL of intermediate density.
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PMID:Atherogenic, dense low-density lipoproteins. Pathophysiology and new therapeutic approaches. 951 39


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