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)

Many avian species demonstrate atherosclerosis and high blood pressure (BP) that are influenced by age, sex, diet, and environment, but show no arteriosclerosis in small vessels. Thus, we aimed to define neural and humoral control of BP in conscious, 32-wk-old female chickens, Gallus gallus. Mean aortic pressure (determined by chronically implanted catheter) was 137.6 +/- 2.0 mm Hg; heart rate was 295 +/- 4 beats/min. Plasma renin activity (PRA), measured by radioimmunoassay of fowl angiotensin I ([Asp1, Val5, Ser9]AI), and plasma angiotensinogen levels were 3.55 +/- 0.31 ng/ml/hr and 1229 +/- 66 ng/ml respectively. Repeated injection of propranolol (4 to 8 mg/kg/day, i.m.) decreased (p less than 0.01) the BP 19.1 +/- 3.0 mm Hg and heart rate 76 +/- 6 beats/min. Acute infusion of propranolol also markedly reduced BP and heart rate, and increased plasma levels of norepinephrine and epinephrine. SQ 14,225 (20 mg/kg/day) reduced BP (p less than 0.01), but BP returned towards original levels unless a higher dose was given. PRA increased 2- to 6-fold. BP also decreased 31.0 +/- 2.1 mm Hg after reserpine treatment, but not after [Sar1, Ile8]AII. These results suggest that in maintaining BP in fowl the beta-adrenergic function is important, whereas the renin-angiotensin system may not have a primary role.
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PMID:Renin-angiotensin and adrenergic mechanisms in control of blood pressure in fowl. 626 58

As part of the multicenter project entitled "Pathobiological Determinants of Atherosclerosis in Youth (PDAY)," we are testing polymorphisms in candidate genes of atherosclerosis and hypertension for associations with arterial lesions in autopsied young persons. In this study, we used temperature gradient gel electrophoresis (TGGE) to type the Met235-->Thr polymorphism in exon 2 of the angiotensinogen gene (AGT) that is associated with essential hypertension in some human populations. In addition to Met235-->Thr, we detected and sequenced four other TGGE variants in exon 2 of AGT. These included two new amino acid substitutions (Thr209-->Ile and Leu211-->Arg) that were found only among black PDAY cases. The frequency of the Ile209 mutation was 0.002 and the frequency of the Arg211 was 0.006 in 260 black PDAY cases. The other two TGGE variants were Tyr248-->Cys and a T-->C substitution at nucleotide position 171 that had been identified in previous studies. We also developed restriction isotyping for rapid typing of each AGT variant using PCR amplification and digestion with diagnostic restriction enzymes.
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PMID:Detection and characterization of new mutations in the human angiotensinogen gene (AGT). 760 42

For more than a decade, the inhibition of the renin-angiotensin system in heart failure has been regarded as pure vasodilator therapy. Consequently, the role of the renin-angiotension system has been seen as contributing to hemodynamic overload by vasoconstriction and volume retention. Meanwhile, clinical experience was indicated that important additional aspects of ACE-inhibition in heart failure are attenuation of the enhanced neuroendocrine activity and reversal or prevention of inappropriate trophic reactions of the overloaded myocardium. In overloaded hearts there is enhanced intracardiac formation of angiotensin due to enhanced expression of angiotensinogen and ACE, and due to accumulation of circulating, nephrogenic active renin. In human hearts, a mast-cell-derived chymase, which is not blocked by ACE-inhibition, contributes to intracardiac angiotensin formation. The enhanced intracardiac angiotensin-II formation in overloaded hearts is involved in coronary constriction, impairment of diastolic relaxation, myocyte enlargement and interstitial fibrosis, which aggravate the diastolic impairment. The major problem in overloaded, hypertrophied cardiocytes is the dedifferentiation with instabilization of Ca(++)-homeostasis due to an altered program of gene expression. Dedifferentiated cardiocytes have a reduced expression of sarcoplasmic reticulum Ca(++)-ATPase and an enhanced expression of the sarcolemmal Na+/Ca(++)-exchanger, resulting in an attenuation of active diastole (Ca(++)-reaccumulation into the sarcoplasmic reticulum), a depressed force-frequency relation, and an enhanced susceptibility for fatal arrhythmias. Furthermore, an enhanced local renin-angiotensin system in distensible coronary and systemic arteries seems to contribute to a reduced releasability of endothelium-derived relaxing factor, probably by reducing bradykinin availability. This modulation of endothelial function appears to contribute to the localization and progression of atheroma development in presence of risks factors for atherosclerosis.
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PMID:Pathophysiology of heart failure and the renin-angiotensin-system. 835 33

Many cell types in myocardial tissue, including cardiocytes, contain receptors for angiotensin-II, but the activation of these receptors requires angiotensin concentrations in the micromolar range, which do not occur in plasma in vivo. However, angiotensins formed locally in the heart can activate these receptors in a paracrine and autocrine mode. In cardiac hypertrophy due to hemodynamic overload, the myocardial angiotensin formation is enhanced due to an augmented expression of angiotensinogen and ACE. Though the mRNA for prorenin is expressed in myocardium, the formation of active renin within the heart has not yet been demonstrated and myocardial renin activity is mainly due to contamination from circulating active renin. Intracoronary application of ACE inhibitors in hypertrophied hearts in vivo and in vitro indicates that the locally formed angiotensin-II contributes to coronary constriction, impairment of diastolic relaxation and marginally to the maintenance of systolic tension development. Angiotensin-II can exert trophic effects on cardiocytes and cardiac fibroblasts, and chronic inhibition of the cardiac RAS by ACE-inhibitors or AT receptor antagonists can induce partial regression of overload hypertrophy, even without normalizing the overload. This anti-trophic action may be partially due to the impairment of the angiotensin axis, but also due to enhancement of bradykinin availability, which results in an augmented release of endothelial anti-trophic signals such as EDRF/NO and prostacyclin. Preliminary evidence is compatible with the hypothesis that an activated local RAS in elastic arteries contributes to the localization and progression of atherosclerosis by suppressing EDRF releasability. However, the anti-atherosclerotic potential of ACE inhibitors and AT receptor antagonists in humans is still unknown.
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PMID:The cardiac renin-angiotensin system: physiological relevance and pharmacological modulation. 851 37

Genetic influences in cerebrovascular disease (CVD) may act either independently or by predisposing to, or modulating, the effect of risk factors such as hypertension. Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction are important in CVD. The angiotensinogen gene has recently been linked with essential hypertension in affected sibships and a particular polymorphism in exon 2 of the angiotensinogen gene, a threonine to methionine substitution at position 235 (M235T), has been associated with pre-eclampsia and hypertension. In this study we examined the relation of M235T polymorphism to cerebrovascular disease and carotid atheroma in 100 consecutive Caucasian patients with internal carotid artery territory ischaemia (TIA or stroke), presenting to a carotid ultrasound service. Forty five age-matched controls (mostly patients' spouses) were also studied. Hypertension was defined as current treatment with anti-hypertensive agents, or SBP > 160 mm Hg or DBP > 95 mm Hg. Twelve of 100 cases (12%) and eight of 45 controls (12%) were homozygous for the T235 allele. T:M allele ratios were 0.34:0.66 in cases and 0.34:0.66 in controls. There was no relation between the polymorphism and either internal carotid stenosis or common carotid artery intima-media thickness. In the cases, mean percentage internal carotid artery stenosis was TT 18.3 (SD 18.7)%, MT 38.0 (27.1)% and MM 36.8 (30.2)%. Mean intima-media thickness was TT 0.87 (0.18) mm, MT 0.95 (0.34) mm and MM 0.88 (0.23) mm. There was no relation between the polymorphism and hypertension (TT 11 of 100 cases, six of 45 controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of association between angiotensinogen polymorphism (M235T) and cerebrovascular disease and carotid atheroma. 852 90

Angiotensin II (Ang II) raises blood pressure (BP) by a number of actions, the most important ones being vasoconstriction, sympathetic nervous stimulation, increased aldosterone biosynthesis and renal actions. Other Ang II actions include induction of growth, cell migration, and mitosis of vascular smooth muscle cells, increased synthesis of collagen type I and III in fibroblasts, leading to thickening of the vascular wall and myocardium, and fibrosis. These actions are mediated by type 1 Ang II receptors (AT1), and may be blocked by losartan, a specific blocker of AT1 receptors. In particular, studies employing losartan have shown that Ang II is an important contributor to BP regulation and plays a significant role in hypertension and in the pathophysiology of vascular damage during the course of hypertension. Ang II is also involved in the process of atherosclerosis and in remodelling and repair processes of the myocardium following myocardial infarction. Finally, increased Ang II is an important part of neurohumoral activation in heart failure. Exciting new discoveries concerned with polymorphisms of genes coding for angiotensin converting enzyme (ACE) and angiotensinogen suggest that Ang II may be genetically associated with increased risk for myocardial infarction, hypertension and left ventricular hypertrophy.
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PMID:Role of angiotensin II in blood pressure regulation and in the pathophysiology of cardiovascular disorders. 858 76

Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated with coronary artery disease (CAD) but no relation between these polymorphisms and coronary atherosclerosis has yet been systematically evaluated. The CORGENE study is a cross-sectional study involving 463 Caucasians who underwent standardized coronary angiography for established or suspected CAD [156 patients with a previous myocardial infarction (MI), 307 without MI]. Four angiographic scores assessing the extent and severity of the coronary lesions were obtained from a double visual analysis of each angiogram, arbitration being achieved by a quantitative measurement. Three different genotypes were analyzed: the angiotensin I-converting enzyme insertion/deletion (ACE I/D) polymorphism, the Met to Thr change at position 235 of the angiotensinogen gene (AGT M235T) and the A to C transition at position 1166 of the angiotensin II type-1 receptor gene (AT1R A1166C). No significant association was observed between these polymorphisms and the clinical characteristics of MI and non-MI subjects. While most classical risk factors were positively correlated with the angiographic scores, no significant relationship could be established with the three genotypes (r ranging from -0.08 to 0.05). Only one significant correlation was observed: between the presence of the AGT 235T allele and the extent of the coronary lesions (r = -0.19, P = 0.04) in patients with low-risk status. These overall results are not in favor of a role of these RAS genetic polymorphisms in the development of coronary atherosclerosis.
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PMID:Genetic polymorphisms of the renin-angiotensin system and angiographic extent and severity of coronary artery disease: the CORGENE study. 900 97

Angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) are major components of the renin-angiotensin systems. An association between myocardial infarction (MI) and the ACE DD genotype of the insertion/deletion (ID) polymorphism in intron 16 of the ACE gene has been reported. However, other similarly designed studies have not found such an association. Angiotensin II, the product of AGT, has a direct effect on vascular tone; and a variant in the AGT gene has been found to be associated with MI in the Japanese. This case-control study was initiated to investigate whether the ACEI/D and AGT M235T polymorphisms are associated with an increased risk for coronary heart disease (CHD) and MI. Our study groups were composed of participants in the National Heart Lung Blood Institute (NHLBI) Family Heart Study (FHS) selected from three population-based studies: two Atherosclerosis Risk in Communities (ARIC) centers (Forsyth County, NC, and Minneapolis, MN), and the Framingham Heart Study. In multivariate analysis within ARIC Caucasians, a significant positive association was found between CHD (controls = 230, cases = 232) and the AGT TT genotype (P = 0.022; OR = 1.84, 1.09-3.10 95% CI). When we restricted the analysis to a low-risk group for CHD (controls = 70, cases = 35) an interaction between the ACE DD and AGT TT genotypes was significant (P = 0.025; OR = 5.02 1.22-20.6 95% CI). After further subsetting low-risk cases to those with a definite MI (controls = 74, cases = 16), we found that the associations with the ACE DD genotype was also significant (P = 0.013, OR = 3.94, 1.28-12.2 95% CI). Comparable tests in the Framingham sample failed to support an association of these markers with CHD. In conclusion, within selected groups the ACE D and AGT 235T alleles are statistically associated with CHD and MI, and there is a synergistic interaction between the two alleles. These results and those from previous studies together suggest that the association of these two loci is neither strong nor consistent and involves a complex interaction among risk factors and genotypes.
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PMID:Associations between candidate loci angiotensin-converting enzyme and angiotensinogen with coronary heart disease and myocardial infarction: the NHLBI Family Heart Study. 903 1

The present study was designed to investigate the development of atherosclerotic lesions in hypertensive transgenic mice carrying both the human renin and angiotensinogen genes (Tsukuba hypertensive mice; THM). THM and C57BL/6J control mice 2 to 3 months of age were fed with either an atherogenic or a normal diet for 14 weeks. Although the systolic blood pressure of either strain remained the same regardless of diet, it was significantly higher in THM than in C57BL/6J on both diets. Total plasma cholesterol concentrations in mice on the atherogenic diet were significantly higher than those in mice fed the normal diet. Lipoprotein profiles of cholesterol in THM were fundamentally similar to those in C57BL/6J on either the atherogenic or normal diet. Compared with controls, however, microscopic analyses revealed accelerated damage of cellular structure in the aortic root in THM fed with the atherogenic diet. Remarkably, the surface area of atherosclerotic lesion in THM was shown by quantitative image analysis to be 4 times larger than that in C57BL/6J on the same atherogenic diet. These findings suggested that hypertension induced by the activated renin-angiotensin system is involved in the development of atherosclerotic lesions. Therefore, THM should be a useful animal model for the study on the pathogenesis of atherosclerosis.
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PMID:Acceleration of atherosclerotic lesions in transgenic mice with hypertension by the activated renin-angiotensin system. 919 59

Myocardial infarction and stroke are the major cause of death in developed countries and are the clinical manifestation of atherosclerosis and hypertension. Both the environmental factors and genetic predisposition have an influence on the pathogenesis of these diseases. Despite we know lots of environmental risk factors and we made important advances in the prevention and treatment of mentioned diseases, our knowledge about the pathogenic linkage between genetic predisposition and cardiovascular diseases is still very little. Activation of the renin-angiotensin system has been proposed as a very important step in the pathogenesis of hypertension and atherosclerosis. In spite of vasoconstrictor activity, angiotensin II can stimulate migration and proliferation of vascular smooth muscle cells, macrophage-foam cells formation, adhesion and aggregation of platelets and fibrinolytic system inhibition. Angiotensin convertin enzyme inhibitors reduce the development of the atherosclerotic process after vascular injury and in hyperlipidemic animals. Blockade of renin-angiotensin system seems to be also effective in secondary prevention of myocardial infarction in men. In sum, the genetic variations inside the renin-angiotensin system which may affect the function of its components might have an influence on genetic predisposition to cardiovascular diseases. The paper deals with the current state of knowledge on association between polymorphic variations in renin gene, angiotensinogen gene, angiotensin converting enzyme gene and AT1 receptor gene and primary hypertension, ischaemic heart disease and myocardial infarction.
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PMID:[The role of DNA polymorphism in the renin-angiotensin system and the pathogenesis of cardiovascular diseases]. 923 64


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