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)

Endothelial cells produce the 21-amino acid peptide endothelin, which is formed from its precursor, big endothelin, via the activity of converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and hypoxia. In vascular smooth muscle, endothelin binds to a specific receptor (ETA-subtype), which activates phospholipase C, leads to the formation of inositol trisphosphate, diacylglycerol (which activates protein kinase C), and increased intracellular Ca2+. In certain blood vessels, the endothelin receptor on vascular smooth muscle is linked to a voltage-operated Ca2+ channel via a G-protein. This explains why Ca2+ antagonists inhibit endothelin-induced contractions in certain, but not all, blood vessels. In the human forearm circulation, Ca2+ antagonists do prevent endothelin-induced contractions and unmask endothelin-induced vasodilation mediated by endothelial prostacyclin production (via the ETB-receptor). The pulmonary circulation plays an important role in the metabolism of endothelin, as the lungs take up large quantities of the peptide during passage. Endothelin has profound vasoconstrictor effects in the pulmonary circulation (and also in bronchial tissue), and its production is augmented in pulmonary hypertension. In systemic hypertension, the circulating endothelin levels appear to be normal. In atherosclerosis and other forms of vascular disease, circulating endothelin levels are increased. Thus, endothelin is a potent mediator in the systemic and pulmonary circulation and, in particular, in diseases of the vasculature.
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PMID:Endothelin: systemic arterial and pulmonary effects of a new peptide with potent biologic properties. 133 60

The fibrinolytic activity (FA) evaluated according to the euglobulin clot lysis time was in haemodialyzed patients (3.0 +/- 0.2 arb. u.) lower than in patients with chronic renal failure treated by conservative methods (4.7 +/- 0.6, p less than 0.05) and than in healthy subjects (4.2 +/- 0.4, p less than 0.05). After stimulation by intravenous administration of 1-deamino-8-D-arginine vasopressin the FA in haemodialyzed patients rose to (4.5 +/- 1.6), less than in conservatively treated (14.1 +/- 2.1, p = 0.06) and than in healthy subjects (18.2 +/- 3.9, p less than 0.001). By using specific methods it was proved that the inadequate rise of FA in haemodialyzed patients after stimulation is conditioned by a defect of the release of the plasminogen tissue activator from the vascular wall. Contrary to healthy subjects (7.0 +/- 1.3 vs. 16.7 +/- 2.3 ng/ml, p less than 0.01) is plasma concentration in haemodialyzed subjects (5.3 +/- 0.5 vs. 7.9 +/- 0.8, NS) did not increase significantly. Repeated examinations of some of the haemodialyzed patients revealed that almost 20 months of regular haemodialysis do not lead to further changes of basal (2.9 +/- 0.3 vs. 2.8 +/- 0.2) nor stimulated (4.2 +/- 0.5 vs. 4.8 +/- 0.9) FA. Basal plasma concentrations of the von Willebrand factor were in the dialyzed patients (89.1 +/- 8.8%) higher than in healthy subjects (67.2 +/- 4.4, p less than 0.05). After stimulation the concentration of the von Willebrand factor increased significantly in healthy subjects (99.1 +/- 4.3, p less than 0.01), but not in dialyzed patients (82.9 +/- 3.1, NS), obviously due to the pathological reactivity of their vascular wall. The above findings may be associated with thromboses and atherosclerosis in patients on long-term dialysis.
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PMID:[Results of studies of indicators of hemostasis in hemodialyzed patients during administration of 1-deamino-8-D-arginine vasopressin]. 163

Endothelial cells can produce contracting factors; endothelin, a 21-amino acid peptide that can control local vascular tone, is the most potent of these factors. Of the three isoforms of endothelin, endothelial cells appear to release primarily endothelin-1. The peptide is formed from its precursor big endothelin via the activity of the endothelin converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin, interleukin-1, and the calcium ionophore A23187. In vascular smooth muscle cells, endothelin binds to a specific receptor that activates phospholipase C and leads to the formation of inositol trisphosphate, diacylglycerol, and increased intracellular calcium levels. In certain blood vessels, the endothelin receptor is linked to a voltage-operated calcium channel via a Gi protein. This may explain why calcium antagonists inhibit endothelin-induced contractions only in certain blood vessels. In the human forearm circulation, calcium antagonists of different classes prevent endothelin-induced contractions. In hypertension, the circulating endothelin levels appear to be normal, whereas the vascular sensitivity to the peptide is reduced in most vascular tissues, but normal and enhanced responses have also been reported. In atherosclerosis and other forms of vascular disease, circulating endothelin levels are augmented, a phenomenon that may be related to an increased formation of the peptide induced by modified forms of low-density lipoproteins.
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PMID:Endothelin. 172 99

A study was conducted to determine if the small (resistance) vessels of the coronary circulation could undergo spasm comparable to that of the major conductance (epicardial) arteries which in the rat measure 275-300 micron in diameter. This information may be relevant to the growing evidence of ischemic myocardial disease without significant coronary atherosclerosis or even spasm of the larger vessels. Vascular corrosion casts of the coronary circulation were prepared in the rat 20 min after intravenous injection of arginine vasopressin, a powerful coronary constrictor substance, under continuous electrocardiographic monitoring. Electrocardiographic changes observed consisted of S-T segment elevation and conduction disturbances, implying ischemic effects on the myocardium. Corrosion casts revealed spasm of smaller arteries only (50-150 micron diameter). Controls (vehicle-injected or untreated) showed no abnormalities of the coronary vasculature. These results suggest that myocardial vessels of this size are comparable in their potential for spasm to the large conductance arteries. Similar findings in patients involving smaller vessels could explain ischemic myocardial events in the absence of significant spasm, or organic stenosing pathology of major coronary arteries. As a corollary, it is suggested that the term "coronary artery spasm" could be enlarged in its definition to include other levels of the coronary circulation rather than that of the large conductance arteries alone.
Atherosclerosis 1987 Sep
PMID:Coronary artery spasm: involvement of small intramyocardial branches. 367 2

Anesthetized rats were sterotaxically implanted with electrodes and electrically stimulated in the lateral hypothalamus. During elevation of the S-T segment on simultaneous precordial electrocardiograms, the heart was perfused with glutaraldehyde-paraformaldehyde fixative and the major coronary arteries prepared for morphometry of luminal dimensions. A similar procedure was performed in a second group receiving intravenous arginine vasopressin (AVP) in place of hypothalamic stimulation. Elevation of the S-T segment was present in these animals as well. Control animals were implanted, not stimulated and otherwise treated in the same way. Morphometry showed that reductions of mean luminal diameter and cross-sectional area of statistical significance occurred in the two experimental groups compared to controls, suggesting that coronary spasm was the cause of the elevated S-T segments. Pooled plasma from separate groups of implanted control and hypothalamically-stimulated animals revealed substantial elevation of AVP levels in the latter raising the possibility that the neuroendocrine was involved in eliciting coronary artery spasm.
Atherosclerosis 1984 Apr
PMID:Coronary artery spasm in the rat induced by hypothalamic stimulation. 672 1

Dehydroepiandrosterone sulfate (DHEAS) is an endogenous steroid having a wide variety of biological effects, but its physiological role remains undefined. Since an age-related decline of DHEAS corresponds to the progressive onset of atherosclerosis, cardiovascular diseases, and overall mortality, we investigated a possible protective role of DHEAS in vascular disease by studying the effects of this hormone (10(-7) to 10(-5) mol/L) on cytosolic free calcium and contractility in different in vitro vascular tissue preparations. DHEAS produced a significant, dose-dependent relaxation of isolated helical strips of rat tail artery precontracted with KCl (60 mmol/L) (89.7 +/- 18.7%, P < .01), arginine vasopressin (3 nmol/L) (27.3 +/- 7.1%, P < .01), and norepinephrine (0.1 mumol/L) (49.2 +/- 18.2%, P < .01). In isolated vascular smooth muscle cells DHEAS reversibly inhibited KCl (30 mmol/L)-induced elevations of cytosolic free calcium to 69.8 +/- 8.4% and 43.8 +/- 7.4% of the control response at 5 x 10(-7) and 5 x 10(-6) mol/L, respectively (P < .05 at both doses). These results provide evidence of a direct vascular action of DHEAS, in doses reflecting circulating levels in vivo, and suggest the possibility that these effects are mediated by modulation of intracellular calcium metabolism. We hypothesize that physiologically, DHEAS may serve to buffer vascular responsiveness to a wide variety of depolarizing and constrictor hormonal stimuli.
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PMID:Effects of dehydroepiandrosterone sulfate on cellular calcium responsiveness and vascular contractility. 749 69

Endothelins (ET) are a family of peptides with potent biological properties. Endothelial cells produce exclusively ET-1 while other tissues produce ET-2 and ET-3. The production of ET requires an increase in intracellular Ca2+. This increase can be induced by physical chemicals (i.e. hypoxia) or receptor-operated stimuli (i.e. thrombin, angiotensin II, arginine vasopressin, transforming growth factor beta 1, interleukin-1). Most of ET is released abluminally towards vascular smooth muscle and less luminally. The main vascular effect of ET are vasodilation (transient), profound and sustained vasoconstriction as well as proliferation of vascular smooth muscle. These biological effects are mediated by distinct receptors. Three ET receptors have been cloned, i.e. ETA-, ETB- and ETC-receptors. In vascular tissue ETA-receptors are expressed on vascular smooth muscle and responsible for vasoconstriction. ETB-receptors are expressed on endothelium and linked to nitric oxide and/or prostacyclin release. Activation of these receptors explains the transient vasodilation with intraluminal application of ET. Vascular smooth muscle cells can express ETB-receptors which contribute to ET-induced vasoconstriction particularly at lower concentrations. The role of the recently cloned ETC-receptor in the vasculature is still uncertain. ET production is increased (as judged from circulating plasma levels) in vascular disease and atherosclerosis in particular, in myocardial infarction and heart failure, pulmonary hypertension and renal disease. ET production is increased in arterial hypertension remains controversial. Non-peptidic ET antagonists have been developed which either block ETA- receptors or ETA- and ETB-receptors simultaneously. The advantage of ETA-receptors is that they leave the endothelium-dependent vasodilation to ET (via ETB-receptor) intact. However, ETB-mediated contraction remains unaffected by these antagonists. In contrast ETA-/ETB-antagonists fully prevent ET-induced vasoconstriction, however, they also inhibit the endothelial effects of the peptide. ET antagonists interfere with the effects of ET in isolated vascular tissue (including that obtained from humans) as well as in vivo. In humans, ETA as well as ETA-/ETB-antagonists inhibit endothelin-induced vasoconstriction. Hence in summary ET are a family of potent peptides with profound effects in the vasculature. Several studies suggest a role of ET in cardiovascular disease. The newly developed ET-antagonists are potent and selective tools to delineate the (patho-)physiological roles of ET and may become a new class of cardiovascular drugs.
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PMID:Endothelin and endothelin antagonists: pharmacology and clinical implications. 771 86

The patient was a 26-year-old man with Cushing's disease who underwent transsphenoidal microscopic surgery for a pituitary microadenoma. His postoperative course was uneventful, but he died suddenly five years after the operation. At autopsy, a ruptured dissecting aneurysm with marked atherosclerosis was observed in the aorta. In the pituitary, a small focus of adrenocorticotropic hormone (ACTH) producing adenoma, possibly residual adenoma, was detected and Crooke's degeneration was observed in the non-tumorous pituitary gland. But immunohistochemical patterns of pituitary hormones in the non-tumorous pituitary gland were normal and the adrenal cortex was unremarkable. In the hypothalamus, corticotropin-releasing hormone immunoreactivity was not detected and arginine vasopressin was sporadically positive. Considering these findings, this patient may have developed subclinical hypercortisolism due to the residual adenoma at the time of autopsy, despite clinical remission. Cushing's syndrome is considered to be a risk factor dissecting aneurysm, and in this case the metabolic changes in Cushing's disease may have influenced the development of the dissecting aneurysm. Periodic cardiovascular re-evaluations should therefore be performed when there is clinical remission of Cushing's syndrome.
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PMID:A case of ruptured dissecting aneurysm 5 years after pituitary microsurgical treatment of Cushing's disease: autopsy findings in the hypothalamic-pituitary-adrenal axis. 795 28

Non-insulin dependent diabetes mellitus (NIDDM) and hypertension are common diseases which are independently associated with insulin resistance/hyperinsulinemia, dyslysidemia, abnormalities of platelet function, and accelerated atherogenesis. The interaction of these independent risk factors is poorly understood. Recently, low density lipoprotein (LDL) receptors have been described, in platelets, and LDL elevates [Ca2+]i in these cells. In this study we have evaluated platelet [Ca2+]i responsiveness to LDL and arginine vasopressin (AVP) in NIDDM patients with (n = 28) and without (n = 13) concomitant hypertension, as well as in normal nondiabetic controls (n = 13). Platelet [Ca2+]i concentration-response curves to LDL for both NIDDM and hypertensive NIDDM were shifted significantly to the left when compared to the normotensive, nondiabetic controls. By contrast, no differences were seen in [Ca2+]i responses to 10 mumol/L AVP among any of the groups. To determine the possible role of hyperinsulinemia in this accentuated [Ca2+]i response to LDL, we measured basal and LDL-stimulated [Ca2+]i in platelets of normal volunteers after insulin treatment (0-100 mU/mL for 30 and 90 min). Insulin did not alter baseline or LDL-stimulated (150 mg/mL) platelet [Ca2+]i. Thus, an enhanced platelet [Ca2+]i response to LDL is characteristic of diabetes, independently of blood pressure. As such, it may also help to explain the enhanced platelet aggregation, endothelial dysfunction, and accelerated atherosclerosis of NIDDM.
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PMID:Increased platelet cytosolic calcium responses to low density lipoprotein in type II diabetes with and without hypertension. 830 68

The heart and kidney are physiologically interconnected. Cardiorenal syndrome (CRS) is a pathological disorder where acute or chronic dysfunction in one organ may induce dysfunction in the other one. Although classical studies have proposed a role for hypertension, dyslipidemia and endothelial dysfunction, CRS should be considered as a complex molecular interplay of neurohumoral pathway activation including the sympathetic nervous system, the renin angiotensin aldosterone axis, the endothelin system and the arginine vasopressin system. This activation may induce vascular inflammation, oxidative stress, accelerated atherosclerosis, cardiac hypertrophy and both myocardial and intrarenal fibrosis with progression of CRS treatment. More recently, epigenetics has opened new pathogenic molecular routes for CRS. This will lead to a more rapid development of novel, safe and effective clinical therapies.
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PMID:Kidney and heart interactions during cardiorenal syndrome: a molecular and clinical pathogenic framework. 2179 45


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