Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thromboendarterectomy is performed to treat chronic thromboembolic pulmonary hypertension with obstruction of main, lobar, or segmental pulmonary arteries. The present study evaluated surgical specimens removed between 1990 and 2001. Medical histories and microscopic slides were reviewed in each case. Study slides were stained with hematoxylin and eosin and Verhoeff-van Gieson and evaluated for thrombus, collagen, elastin, atherosclerosis, hemosiderin, calcification, and inflammation. The study group comprised 54 patients (30 women and 24 men), ranging in age from 33 to 77 years (mean, 58 years). Clinically, 28 (52%) had a history of deep leg vein thrombosis and 42 (78%) had a history of pulmonary embolism; 24 (44%) had both events. Coagulation abnormalities were documented in 15 (28%); autoimmune or hematologic disorders, in 8 (15%). Pulmonary thromboendarterectomy was bilateral in 52 patients (96%) and right-sided in 2. Six patients also had obstructions resected from the main pulmonary arteries. Obstruction limited to segmental arteries occurred only in women. Grossly, right-sided specimens were larger than left-sided ones (P = 0.003). Microscopically, ages of thrombi were uniform in 72% and variable in 28%. Intima was thickened in all patients and consisted of collagen (100%), elastin (67%), hemosiderin (56%), inflammation (53%), atherosclerosis (32%), and calcification (15%). We determined that pulmonary thromboendarterectomy was performed most often in middle-aged and elderly patients with a history of deep venous thrombosis or pulmonary embolism. Less than 50% of the patients had an identifiable coagulation, autoimmune, or hematologic abnormality. Most patients had bilateral disease and resections. Right-sided specimens were significantly larger than left-sided specimens, and lower lobe involvement was more common than involvement elsewhere. Resected tissues most commonly exhibited old organized thrombus.
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PMID:Surgical pathology of pulmonary thromboendarterectomy: a study of 54 cases from 1990 to 2001. 1469 15

The endothelins are synthesized in vascular endothelial and smooth muscle cells, as well as in neural, renal, pulmonal, and inflammatory cells. These peptides are converted by endothelin-converting enzymes (ECE-1 and -2) from 'big endothelins' originating from large preproendothelin peptides cleaved by endopeptidases. Endothelin (ET)-1 has major influence on the function and structure of the vasculature as it favors vasoconstriction and cell proliferation through activation of specific ET(A) and ET(B) receptors on vascular smooth muscle cells. In contrast, ET(B )receptors on endothelial cells cause vasodilation via release of nitric oxide (NO) and prostacyclin. Additionally, ET(B) receptors in the lung are a major pathway for the clearance of ET-1 from plasma. Indeed, ET-1 contributes to the pathogenesis of important disorders as arterial hypertension, atherosclerosis, and heart failure. In patients with atherosclerotic vascular disease (as well as in many other disease states), ET-1 levels are elevated and correlate with the number of involved sites. In patients with acute myocardial infarction, they correlate with 1-year prognosis. ET receptor antagonists have been widely studied in experimental models of cardiovascular disease. In arterial hypertension, they prevent vascular and myocardial hypertrophy. Experimentally, ET receptor blockade also prevents endothelial dysfunction and structural vascular changes in atherosclerosis due to hypercholesterolemia. In experimental myocardial ischemia, treatment with an ET receptor antagonist reduced infarct size and prevented left ventricular remodeling after myocardial infarction. Most impressively, treatment with the selective ET(A) receptor antagonist BQ123 significantly improved survival in an experimental model of heart failure. In many clinical conditions, such as congestive heart failure, both mixed ET(A/B )as well as selective ET(A) receptor antagonism ameliorates the clinical status of patients, i.e. symptoms and hemodynamics. A randomized clinical trial showed that a mixed ET(A/B) receptor antagonist effectively lowered arterial blood pressure in patients with arterial hypertension. In patients with primary pulmonary hypertension or pulmonary hypertension related to scleroderma, treatment with a mixed ET(A/B) receptor antagonist resulted in an improvement in exercise capacity. ET receptor blockers thus hold the potential to improve the outcome in patients with various cardiovascular disorders. Randomized clinical trials are under way to evaluate the effects of ET receptor antagonism on morbidity and mortality.
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PMID:Therapeutic potential for endothelin receptor antagonists in cardiovascular disorders. 1472 28

Schimke-immuno-osseous dysplasia (SIOD) is a multisystem disorder caused by a mutation of the chromatin remodeling protein. The main clinical findings are spondyloepiphyseal dysplasia with disproportional growth deficiency, nephrotic syndrome with focal and segmental glomerulosclerosis, and defective cellular immunity. Transitory ischemic attacks due to vaso-occlusive processes are still an untreatable and life-limiting complication in patients with SIOD. The underlying pathophysiology of vaso-occlusive processes in SIOD is unclear. We report the clinical and pathological findings of the eldest published patient with the severe form of SIOD, who died at the age of 23 years due to pulmonary hypertension with subsequent right heart failure. The autopsy revealed a severe generalized atherosclerosis including the brain, heart, and pulmonary arteries. However, the kidney that was transplanted at the age of 5 years showed a good graft function without glomerular sclerosis and with only minimal nephrosclerosis on histology. Thus, the absence of severe vaso-occlusive processes in the transplanted organ and in the severely atherosclerotic host may indicate that the vaso-occlusive processes in SIOD are not caused by post-transplant cardiovascular morbidity such as arterial hypertension and hyperlipidemia. Instead, vascular factors of the host such as endothelial dysfunction may explain the pathophysiology of atherosclerosis in SIOD.
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PMID:Generalized atherosclerosis sparing the transplanted kidney in Schimke disease. 1505 43

Endothelins are a family of three peptides of 21 amino acids with strong vasoconstrictor effects. The three peptides are encoded by three different genes and derived from precursors (" big endothelins") which are cleaved by metalloproteases, named endothelin-converting enzyme. Two receptors have been cloned, ET-A and ET-B which bind the three endothelins with various affinities. The diverse expression pattern of the endothelin system (ET) components is associated with a complex pharmacology and its counteracting physiological actions. New modulators of the ET system have been described : retinoic acid, leptin, prostaglandins, hypoxia. Endothelins can be considered as regulators working in paracrine and autocrine fashion in a variety of organs in different cellular types. The ET system has beneficial and detrimental roles in mammals. The different components have been shown to be essential for a normal embryonic and neonatal development, for renal homeostasis and maintenance of basal vascular tone. They are involved in physiological and tumoral angiogenesis. They affect the physiology and pathophysiology of the liver, muscle, skin, adipose tissue and reproductive tract. The endothelin system participates in the development of atherosclerosis as well as pulmonary hypertension, and mediates cardiac remodeling in heart failure. Elaboration of new animal models (knock-out, pathophysiological models em leader ) will allow the clear genetic dissection of physiological and pathophysiological roles of the endothelin system.
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PMID:[What is the role of endothelin system?]. 1506 80

Sarpogrelate is a selective 5-hydroxytryptamine receptor subtype 2A (5-HT2A) antagonist. It is metabolised to racemic M-1 and both enantiomers of M-1 are also antagonists of 5-HT2A receptors. Sarpogrelate inhibits responses to 5-HT mediated by 5-HT2A receptors such as platelet aggregation, vasoconstriction and vascular smooth muscle proliferation. There is no information available on the pharmacokinetics of sarpogrelate. Sarpogrelate is efficacious in animal models of thrombosis, coronary artery spasm, atherosclerosis, restenosis, peripheral vascular disease, pulmonary hypertension, ischaemic heart disease, myocardial infarction, diabetes and kidney disease. Small clinical trials indicate that sarpogrelate may be beneficial in the treatment of coronary artery disease, angina, restenosis, heart valve prostheses surgery, diabetes mellitus, Raynaud's phenomenon, systemic sclerosis and Buerger's disease. Larger, randomised, double-blind, placebo-controlled clinical trials of sarpogrelate in intermittent claudication, coronary artery disease, restenosis and diabetes should be considered.
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PMID:Sarpogrelate: cardiovascular and renal clinical potential. 1521 24

Obstructive sleep apnea (OSA) is a common medical condition that occurs in approximately 5% to 15% of the population. The pathophysiology of OSA is characterized by repetitive occlusions of the posterior pharynx during sleep that obstruct the airway, followed by oxyhemoglobin desaturation, persistent inspiratory efforts against the occluded airway, and termination by arousal from sleep. Obstructive sleep apnea is associated with daytime sleepiness and fatigue, likely due to fragmented sleep from recurrent arousals. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA and that OSA is a risk factor for the development of hypertension. Recent studies show that OSA may be implicated in stroke and transient ischemic attacks. Obstructive sleep apnea appears to be associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with preexisting pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified to be important in the development of atherosclerosis. Obstructive sleep apnea is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, and plasminogen activator inhibitor, and reduced fibrinolytic activity. Obstructive sleep apnea has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease.
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PMID:Obstructive sleep apnea and cardiovascular disease. 1530 32

Obstructive sleep apnea (OSA) occurs commonly in the U.S. population and is seen in both obese as well as non-obese individuals. OSA is a disease characterized by periodic upper airway collapse during sleep, which then results in either apnea, hypopnea, or both. The disorder leads to a variety of medical complications. Neuropsychiatric complications include daytime somnolence, cognitive dysfunction, and depression. Increased incidence of motor vehicle accidents has been documented in these patients and probably reflects disordered reflex mechanisms or excessive somnolence. More importantly, vascular disorders such as hypertension, stroke, congestive cardiac failure, arrhythmias, and atherosclerosis occur frequently in these patients. The lungs may be affected by pulmonary hypertension and worsening of asthma. Recent data from several laboratories demonstrate that obstructive sleep apnea is characterized by an inflammatory response. Cytokines are elaborated during the hypoxemic episodes leading to inflammatory responses as marked clinically by elevated C-reactive protein (CRP). As elevated CRP levels are considered markers of the acute phase response and characterize progression of vascular injury in coronary artery disease, it is likely that obstructive sleep apnea could lead to worsening of vasculopathy. Moreover, as inflammatory mechanisms regulate bronchial asthma, it is also likely that cytokines and superoxide radicals generated during hypoxemic episodes could exacerbate reactive airway disease. Patients with Cough, Obstructive sleep apnea, Rhinosinusitis, and Esophageal reflux clustered together can be categorized by the acronym, "CORE", syndrome. The purpose of this manuscript is to review the inflammatory responses that occur in patients with obstructive sleep apnea and relate them to the occurrence of cardiopulmonary disease.
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PMID:Obstructive sleep apnea, inflammation, and cardiopulmonary disease. 1535 23

In this article we summarize the available information regarding the epidemiology, the pathophysiology as well as the risk factors and complications of the sleep apnea syndrome (SAS). Central, obstructive and mixed forms of SAS are known, however, the obstructive form is (resulting from the actual high prevalence of obesity) definitely the most frequent. Latest years of experimental and clinical research have pointed towards the clinical importance of this sleep related breathing disorder. High prevalence in the population and especially the cardiovascular complications (e. g. systemic and pulmonary hypertension, atherosclerosis, arrhythmias) have contributed to the recent increase in knowledge about SAS. Nevertheless, there are numerous unsolved problems and unanswered questions in the pathophysiology of SAS. Future studies should, thus, provide us with more information and shed light on regarding the hidden mysteries of SAS.
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PMID:Sleep apnea syndrome and its complications. 1535 82

The objective of this study was to determine the lipoprotein profile of limited cutaneous systemic sclerosis (LcSSc). Fasting lipids were determined in 24 female patients and 24 healthy age-matched and sex-matched controls. Exclusion criteria were conditions that induce an altered lipid profile. Lipoprotein levels of risk were determined in accordance with the National Cholesterol Education Program (NCEP). Significantly lower levels of high-density lipoprotein (HDL) cholesterol (47.6+/-12.4 mg dL(-1) vs. 58.2+/-12.3 mg dL(-1); P=0.003) and total cholesterol (197.0+/-40.7 mg dL(-1) vs. 222.0+/-34.0 mg dL(-1); P=0.02) were observed in LcSSc patients than in controls. The presence of anti-centromere antibodies (ACA) was also associated with lower HDL levels (45.0+/-12.1 mg dL(-1)) compared to ACA-negative patients and controls (50.2+/-12.6 and 58.2+/-12.3 mg dL(-1), respectively, P=0.01). The only clinical variable associated with low HDL levels was pulmonary hypertension (PH) (33.6+/-2.3 mg dL(-1) vs. 49.6+/-11.9 mg dL(-1), P=0.01). No significant correlation was observed among HDL levels and ESR (r=-0.313; P=0.14), CRP (r=-0.296; P=0.16), or BMI (r=-0.263; P=0.21). Remarkably, a higher percentage of risk HDL levels was identified in LcSSc patients (41.6%) than in healthy controls (8.3%) (P=0.02). Our data suggest that LcSSc patients, particularly those who are ACA positive, have an adverse lipid profile characterized by low HDL levels, a known independent risk for CAD in women. The relevance of this finding for the development of atherosclerosis in this disease must be confirmed by epidemiological studies.
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PMID:Lipoprotein profile in limited systemic sclerosis. 1628 68

Caveolae are vesicular organelles (50-100-nm in diameter) that are particularly abundant in cells of the cardiovascular system, including endothelial cells, smooth muscle cells, macrophages, cardiac myocytes and fibroblasts. In these cell types, caveolae function both in protein trafficking and signal transduction, as well as in cholesterol homeostasis. Caveolins are the structural proteins that are both necessary and sufficient for the formation of caveolae membrane domains. Caveolins 1 and 2 are co-expressed in most cell types, while the expression of caveolin-3 is muscle-specific. Thus, endothelial cells and fibroblasts are rich in caveolins 1 and 2, while cardiac myocytes and skeletal muscle fibers express caveolin-3. In contrast, smooth muscle cells express all three caveolins (Cav-1, -2, and -3). Mechanistically, caveolins interact with a variety of downstream signaling molecules, including Src-family tyrosine kinases, p42/44 mitogen activated protein (MAP) kinase, and endothelial nitric oxide synthase (eNOS), and hold these signal transducers in the inactive conformation until activation by an appropriate stimulus. In many ways, caveolins serve both to compartmentalize and regulate signaling. Recent studies using caveolin-deficient mouse models dramatically show that caveolae and caveolins play a prominent role in various human patho-biological conditions, especially those related to the cardiovascular system. These disease phenotypes include: atherosclerosis, cardiac hypertrophy, cardiomyopathy, pulmonary hypertension, and neointimal hyperplasia (smooth muscle cell proliferation). In addition, caveolins play a significant role in other disease phenotypes, such as cancer, diabetes, bladder dysfunction, and muscular dystrophy, as we discuss in this review. Thus, caveolin-deficient mice will serve as important new animal models to dissect the intricate role of caveolae and caveolins in the pathogenesis of human diseases.
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PMID:The Caveolin genes: from cell biology to medicine. 1576 30


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