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)

A morphometric study of atherosclerotic lesions of the vessels was conducted in males dying of cancer of the stomach and lungs, and in females dying of cancer of the stomach, lungs, uterus, breast and ovaries. In total, 918 observations were studied, the age of the deceased ranging from 30 to 79 years. The severity of the atherosclerotic lesions in the vessels of those who died of malignant tumors was compared to that in normal individuals. The material was compiled and examined in accordance with the program and method developed by WHO expertpathologists (Uemura et al.). In those who died of cancer of the stomach, uterus and breast the severity of coronary atherosclerosis was much milder than in the normals; however, no important differences were revealed between these groups as to the severity of atherosclerosis of the aorta. In lung cancer in males and in ovarian cancer in females under 50 years of age a distinct enhancement of the atherosclerotic process in the aorta was observed, and less-in the coronaries. In females dying of lung cancer the severity of atherosclerosis of the aorta was the same as in the normals, and in the coronaries - even milder.
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PMID:[Characteristics of the development of arteriosclerosis of the aorta and coronary arteries in patients with cancer of different organs]. 122 58

The effects of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotensin I converting enzyme inhibitor, on cardiovascular, visceral and renal functions and on hemodynamics, were studied in various experimental animals. Even at a high dose of 100 mg/kg p.o. benazepirl hydrochloride had no influence on the respiration, heart rate and ECG of normotensive anesthetized cats and, except at higher doses, had little effect on the contractile tension of mammalian isolated atrium, ileum, trachea, stomach fundus strips, vas deferens or uterus. Benazepril hydrochloride even at a high dose of 100 mg/kg p.o. had little effect on spontaneous uterine motility, charcoal transportation and gastrointestinal tract motility. In addition, it did not cause gastric irritation, alter the secretion of gastric and biliary juices, and did not affect the tension of the nictitating membrane or the twitch tension of the gastrocnemius muscle in various experimental animals. Benazepril hydrochloride had no effect on the blood glucose and cholesterol levels in alloxan-induced diabetic rats but decreased the triglyceride and total cholesterol levels in normotensive rats at a dose of 30 mg/kg p.o. Benazepril hydrochloride at 3 mg/kg.day s.c. for 10 weeks caused a significant decrease in aortic atherosclerosis without reducing hypercholesterolemia in cholesterol-fed rabbits. Benazepril hydrochloride at a high dose of 100 mg/kg p.o. showed no effect on the urine volume and urinary excretion of electrolytes but decreased PSP excretion in normotensive rats. At a dose of 3 or 10 mg/kg.day p.o. for 4 weeks benazepril hydrochloride inhibited the increase in the excretion of urinary protein in DOCA/salt spontaneously hypertensive rats. It caused hemolysis at concentrations as high as 0.1-1% in rabbits, however, even at a high dose of 100 mg/kg p.o. it did not affect red blood cell fragility in rats, and, except at a high dose of 10(-4) g/ml, showed little effect on the platelet aggregation response induced by collagen or arachidonic acid in rabbits. From these results, benazepril hydrochloride is considered to be a safe and well-tolerated addition to the therapeutic armamentarium of cardiovascular drugs.
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PMID:General pharmacology of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride. Effects on cardiovascular, visceral and renal functions and on hemodynamics. 179 19

Unopposed estrogens, both exogenous and endogenous, increase the risk of endometrial cancer although the magnitude of the association between estrogen replacement therapy and adenocarcinoma has been exaggerated by the epidemiologic case-control studies. Not all postmenopausal women need estrogen replacement therapy since some produce sufficient endogenous estrogens to remain asymptomatic and prevent atrophic vaginitis, osteoporosis and atherosclerosis. However, within this group may be those at risk for endometrial cancer, so they need to be identified and treated with cyclic progestogens. Sequential oral contraceptives did not protect young women from adenocarcinoma of the endometrium because of too little progestogen for too short a duration in view of the relatively high dosage of estrogen. However, combination birth control pills significantly decrease the risk for endometrial carcinoma. Endometrial hyperplasia is a precancerous lesion in some women and can be effectively reversed with 10-13 days of progestogen monthly in at least 98% of patients. The progestogen challenge test has been devised to identify postmenopausal women at greatest risk for adenocarcinoma. It should be administered to all postmenopausal women with an intact uterus. This includes asymptomatic women, patients receiving estrogen replacement therapy and women being evaluated for hormone therapy. If there is a positive response to the progestogen challenge, as manifested by withdrawal bleeding, then the progestogen should be continued for 13 days each month for as long as withdrawal bleeding results. If there is no response then the progestogen challenge test should be repeated at each annual examination. Universal use of the progestogen challenge test should prevent nearly all endometrial cancers.
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PMID:The role of hormones in the etiology and prevention of endometrial cancer. 379 26

It has been suggested that HDL may protect against clinical complications to atherosclerosis by stimulating cholesterol elimination from arterial tissue. To test this hypothesis alphalipoprotein cholesterol was related to arterial cholesterol in a group of women undergoing hysterectomy due to uterus myoma. A significant, inverse correlation between alphalipoprotein cholesterol and the cholesterol: DNA ratio in arterial tissue with intact endothelium was observed. This supports the hypothesis that HDL may participate in cholesterol removal from arterial tissue. Available data seem to favour the possibility that cholesterol is primarily effective in the elimination of cholesterol from the extracellular compartment.
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PMID:Alphalipoprotein cholesterol and arterial cholesterol in human uterine arteries. 721 45

Typha angustata Bony et Chaub. is a traditional Chinese medicine, commonly used in China for a variety of clinical disorders, including atherosclerosis, cardiovascular diseases, uterus contraction, and wound healing. The effect of the pollen of Typha angustata on the bone inductive capacity of demineralized bone matrix is studied here. Demineralized bone matrix soaked with saline solution was implanted in 8-mm defects in rat calvaria. After surgery all rats received a 0.2-ml injection in the defect sites of Typha angustata extract, plasma, or saline 3 times weekly for 2 to 4 weeks. The repair of bone defects was evaluated by radiography and by histology at 2 and 4 weeks after surgery. Results indicated that the 3% Typha angustata extract and demineralized bone matrix combination produced substantially more bone than demineralized bone matrix alone, while plasma plus demineralized bone matrix induced the same amount of bone formation as Typha angustata extract plus demineralized bone matrix. The osteoinductive potential increased in a dose dependent manner, 3% Typha angustata extract plus demineralized bone matrix produced more bone than the 0.6% Typha angustata extract plus demineralized bone matrix at 2 and 4 weeks. This study demonstrates that an extract of the pollen of Typha angustata is capable of enhancing the osteoinductive potential of demineralized bone matrix.
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PMID:Effects of pollen from Typha angustata on the osteoinductive potential of demineralized bone matrix in rat calvarial defects. 807 Feb 2

The type I cGMP-dependent protein kinase (cGK) is one of the major pathways for the cGMP cascade and has been demonstrated to inhibit platelet aggregation, relax smooth muscle cells, and control cardiocyte contractility. There are two subtypes of the type I cGK, cGKIalpha and cGKIbeta. The former is more sensitive to cGMP than the latter. In humans, cGKIbeta cDNA was isolated, but the full structure and tissue-specific gene expression of cGKIalpha have not been determined. The significance of cGK in human cardiovascular diseases has not been investigated at the molecular level. In the present study, we isolated the full-length human CGKIalpha cDNA (-36 to +2177; the translation start site: +1) enclosing the 671-amino acid protein. Nucleotides +267 to +2177 of the isolated cDNA were identical to the corresponding nucleotides of human cGKIbeta cDNA. Southern blot analysis suggested that human cGKIalpha and cGKIbeta are generated by alternative splicing of a single gene assigned to chromosome 10. By Northern blot analysis, we detected abundant human cGKIalpha mRNA (7.0 kb) in the aorta, heart, kidneys, and adrenals. In contrast, human cGKIbeta mRNA (7.0 kb) was detected abundantly only in the uterus. In cultured vascular smooth muscle cells, the type I cGK mRNA concentration was reduced to 10% of the basal level by 4 x 10(-10) mol/L platelet-derived growth factor. Angiotensin II (10(-8) mol/L), transforming growth factor-beta (4 x 10(-11) mol/L), and tumor necrosis factor-alpha (6 x 10(-6) mol/L) also exhibited an inhibitory effect on type I cGK gene expression. These findings suggest a pathophysiological implication of the type I cGK in cardiovascular diseases, including hypertension and atherosclerosis.
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PMID:cDNA cloning and gene expression of human type Ialpha cGMP-dependent protein kinase. 861 2

The reality of the atheroprotective effect of estrogens is still a matter of debate, and its unknown mechanisms could involve favorable changes in blood lipids and lipoproteins and/or direct action at the level of the arterial wall. We used the recently developed animal model of atherosclerosis constituted by apolipoprotein E-deficient mice in an attempt to clarify these issues. Male and female animals, fed a low-fat chow diet, were treated with increasing doses of 17 beta-estradiol (E2) after castration and compared with testosterone treated and uncastrated (intact) animals. Total serum cholesterol, LDL-cholesterol, and HDL-cholesterol concentrations decreased under E2 treatment in each sex and were weakly correlated with lesion area. However, a highly significant correlation between lesion area and serum E2 levels also suggested a direct action of E2 on cells of the vascular wall. A dose-response curve analysis revealed that these activities were sex-dependent, with females being nearly twice as sensitive to E2 as males. It also revealed that the atheroprotective activity was recruited at higher E2 concentrations than those needed by other E2 target tissues such as uterus or functions such as apoA-1 and LDL production and/or clearance rates.
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PMID:17 beta-estradiol prevents fatty streak formation in apolipoprotein E-deficient mice. 940 42

Raloxifene has been shown to have estrogen agonist effects on bone and cholesterol metabolism while having estrogen antagonist effects on mammary gland and uterus. Reported here are the results of a study to determine whether raloxifene had the estrogen agonist effect of inhibiting coronary artery atherogenesis and to compare its effects with those of traditional conjugated equine estrogens (CEE) treatment. Ovariectomized (surgically postmenopausal) cynomolgus monkeys were fed a moderately atherogenic diet and treated with a placebo, raloxifene (1 mg/kg x day), raloxifene (5 mg/kg x day), or CEE (Premarin) at a dose that mimicked that of 0.625 mg/day in women. The effects of raloxifene on plasma lipid concentrations were generally comparable to those reported in postmenopausal women treated with raloxifene: reductions in low density lipoprotein cholesterol concentrations and no significant effects on high density lipoprotein cholesterol. We found no evidence that raloxifene had an estrogen agonist effect on coronary arteries. Treatment with CEE resulted in about a 70% reduction in coronary artery plaque size relative to that in the placebo group, whereas neither the low nor the high dose of raloxifene had an effect on coronary artery plaque size. The low dose raloxifene group had about 2 times more atherosclerosis and the high dose group had about 3 times more atherosclerosis than the CEE group.
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PMID:Lack of effect of raloxifene on coronary artery atherosclerosis of postmenopausal monkeys. 970 84

Epidemiological observations, clinical studies, and basic laboratory research suggest that oestrogen replacement therapy is associated with beneficial cardiovascular effects in postmenopausal women. Oestrogen has a multitude of biological effects that may account for this apparent benefit (which remain to be proven in randomized clinical trials), including favourable effects on the lipid profile, a direct effect on the vascular endothelium with increased nitric oxide bioactivity, and improved fibrinolysis. However, long-term oestrogen therapy increases the risk of breast and endometrial cancers. Raloxifene, a benzothiophene derivative that binds to the oestrogen receptor, is a selective oestrogen receptor modulator, producing oestrogen-agonistic effects in some tissues (liver, bone), and oestrogen-antagonistic effects in others (breast, uterus), and may prove to be an option for women with atherosclerosis and its associated risk factors who might benefit from oestrogen therapy. This review updates the current knowledge of the biological effects of oestrogen and selective oestrogen receptor modulators of potential cardiovascular importance in postmenopausal women.
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PMID:Effects of oestrogens and selective oestrogen receptor modulators on serum lipoproteins and vascular function. 986 94

Selective estrogen receptor modulators (SERMs) represent a growing class of compounds that act as either estrogen receptor agonists or antagonists in a tissue-selective manner. Preclinical and clinical studies have shown that estrogen has favorable effects on serum lipids and might affect processes at the blood vessel wall to inhibit atherosclerosis. SERMs with the appropriate selectivity profile offer the opportunity to dissociate these favorable cardiovascular effects of estrogen from its unfavorable stimulatory effects on the breast and uterus. This article reviews the data from both animal and human studies that document the cardiovascular effects of SERMs and discusses the clinical implications of these results.
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PMID:The Potential of SERMs for Reducing the Risk of Coronary Heart Disease. 1048 Nov 63


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