Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impaired elastin fiber assembly is observed in the fetal ductus arteriosus (DA), associated with a reduced concentration of elastin binding protein (EBP), a 67-kDa galactolectin. It is also seen in cultured aortic (Ao) smooth muscle cells (SMC) following the release of the EBP by glycosaminoglycans rich in N-acetylgalactosamine, such as chondroitin sulfate (CS). In the DA, impaired elastin fiber assembly is observed in conjunction with intimal thickening associated with increased migration of SMC into the subendothelium, a feature we previously related to increased production of fibronectin. In this report, we determined whether SMC use the EBP to attach to an elastin substrate, whether shedding of the EBP promotes SMC migration through a three-dimensional network of pure elastic laminae prepared from sheep aorta, and whether the latter is associated with increased production of fibronectin. We observed reduced attachment to elastin-coated surfaces of DA SMC deficient in EBP compared to Ao SMC. Addition of CS but not heparan sulfate (a glycosaminoglycan which does not induce EBP shedding) decreased Ao SMC attachment to elastin, as did preincubation with VGVAPG elastin-derived peptides which saturate the EBP. The immunolocalization of cell surface EBP suggested that cells can quickly replace EBP released from their surfaces by CS treatment. The magnitude of CS-induced impaired attachment of SMC to elastin was dose dependent and could be further increased by the administration of cyclohexamide and sodium azide. Also, the reversibility of CS-induced detachment was prevented by monensin. This suggests that a process of new synthesis and intracellular transport of the EBP was necessary to replace the EBP molecules released from the cell surface by CS treatment. In the migration assay, both DA and Ao SMC attached to the top of an elastin membrane, but only DA SMC deficient in EBP migrated through the laminae. Addition of CS, which induced shedding of EBP, resulted in Ao SMC migration associated with increased synthesis of fibronectin. We postulate that CS-induced release of EBP from SMC surfaces causes cell detachment from elastin and an increase in fibronectin synthesis, processes which may be critical in promoting SMC migration associated with intimal thickening developmentally in the DA and perhaps also in vascular disease.
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PMID:Vascular smooth muscle cell detachment from elastin and migration through elastic laminae is promoted by chondroitin sulfate-induced "shedding" of the 67-kDa cell surface elastin binding protein. 133 80

Patients with insulin-dependent diabetes mellitus have an increased mortality and morbidity due to vascular complications. Nitric oxide from the vascular endothelium contributes to the control of normal vascular tone, and endothelial dysfunction has been implicated in the pathogenesis of diabetic vascular disease. In this study we have examined basal and stimulated nitric oxide-mediated vasodilatation in insulin-dependent diabetics and age- and sex-matched healthy controls. Drugs were infused locally into the brachial artery and forearm blood flow measured using venous occlusion plethysmography. Noradrenaline and NG-monomethyl-L-arginine produced similar reductions in resting forearm blood flow in healthy controls. However, in the diabetics, NG-monomethyl-L-arginine was significantly less effective than noradrenaline. Comparing between groups, the response to NG-monomethyl-L-arginine was also significantly less in the diabetics compared with the healthy controls. The response to sodium nitroprusside was significantly less in the diabetics compared with the healthy controls, whereas the responses to both acetylcholine and verapamil were the same in the two groups. The results provide evidence for an abnormality of basal nitric oxide-mediated dilatation in the forearm arterial bed of patients with insulin-dependent diabetes mellitus, and suggest that the vascular smooth muscle is less sensitive to nitric oxide.
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PMID:Inhibition and stimulation of nitric oxide synthesis in the human forearm arterial bed of patients with insulin-dependent diabetes. 146 3

Non-insulin-dependent diabetes is associated with a 2-3 fold increased risk of cardiovascular disease. The poor relationship between this risk and either glycaemic control or diabetes duration suggests that some other aspect of the diabetic state, and not hyperglycaemia per se, mediates this risk. This other aspect of diabetes does not comprise alterations in recognized cardiovascular risk factors such as blood pressure or lipids, as the major component of the excess risk is in those diabetics with low levels of the other risk factors. It thus appears that there may be some factors that predispose both to diabetes and to cardiovascular disease. In insulin-dependent diabetics most of the excess risk of cardiovascular disease occurs in subjects with proteinuria, and microalbuminuria or proteinuria in non-insulin-dependent diabetics also substantially increases cardiovascular risk. Although changes in recognized risk factors in diabetics with nephropathy may partly explain these observations, we and others have shown that microalbuminuric non-diabetics also have a markedly increased prevalence of cardiovascular disease and substantially increased cardiovascular mortality. The observations that in insulin-dependent diabetics nephropathy shows family clustering and that these patients have elevated sodium lithium counter-transport rate, a possible genetic marker for the vascular complications of hypertension, have led to the suggestion that microalbuminuria may be a marker of a genetic predisposition to vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microalbuminuria: a genetic link between diabetes and cardiovascular disease? 148 48

The angiotensin converting enzyme (ACE) inhibitors are a group of effective drugs with a unique mechanism of action. These drugs have proven to be useful for hypertension and congestive heart failure. Early clinical trials of captopril used doses that are now known to be inappropriately high, and dose-related adverse effects were observed frequently. The recognition that lower doses are effective has reduced the incidence of adverse reactions and resulted in improved patient tolerance. When patients are properly selected and correctable risk factors are removed, serious side effects are uncommon. Unfortunately, the early reputation of nephrotoxicity persists, as does the belief that significant blood dyscrasias, endocrine effects and rash are serious risks for the average patient. After wide use of captopril, enalapril and lisinopril, and investigational trials of nearly a dozen newer agents, a sufficiency of clinical observation, experimental evidence and accurate postmarketing recording of events is accumulating to allow insight into the major toxicities with regard to more intelligent patient selection, more rational dosing and proper identification of risk factors. The most common adverse reactions are cough and skin rash. It appears that the agents are generally not cross-reactive with regard to skin rash, although it is not clear whether this effect is drug-specific or class-specific with regard to cough. Statistically but not clinically significant lowering of haemoglobin and hematocrit is common; these effects are inconsequential in most patients. Neutropenia, once thought to be prevalent, now appears to be so only in patients with autoimmune or collagen-vascular disease; the majority of patients outside these groups are at low risk. Hyperkalaemia is a frequent occurrence. This should not be surprising in view of the effect of the ACE inhibitors on plasma aldosterone. When dietary potassium intake is regulated and sources of altered potassium excretion are identified, hyperkalaemia is seldom a serious problem. Identification of sodium and water deficits allows correction before the drugs are started, and the frequency of hypotension and hyperkalaemia caused by the drugs is quite low if these factors are properly managed. An unexpected finding emerging in recent years is the dry cough associated with ACE inhibitor therapy. Its mechanism is not definitely known. Nonsteroidal anti-inflammatory drugs may control this symptom in some patients. The frequent observation of proteinuria in patients taking ACE inhibitors has gained notice and sometimes caused undue alarm. It is difficult to separate disease effects in diabetes and hypertension from true drug effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update. 153 95

Cardiovascular disease represents the major cause of morbidity and mortality in noninsulin-dependent diabetic patients. While it was once thought that atherosclerotic vascular disease was responsible for all of these adverse effects, recent studies support the notion that one of the major adverse complications of diabetes is the development of a diabetic cardiomyopathy characterized by defects in both diastolic and systolic function. Contributing to the development of the cardiomyopathy is a shift in myosin isozyme content in favor of the least active V3 form. Also defective in the noninsulin-dependent diabetic heart is regulation of calcium homeostasis. While transport of calcium by the sarcolemmal and sarcoplasmic reticular calcium pumps are minimally affected by noninsulin-dependent diabetes, significant impairment occurs in sarcolemmal Na(+)-Ca2+ exchanger activity. This defect limits the ability of of the diabetic heart to extrude calcium, contributing to an elevation in [Ca2+]i. Also promoting the accumulation of calcium by the diabetic cell is a decrease in Na+, K+ ATPase activity, which is known to increase [Ca2+]i secondary to a rise in [Na+]i. In addition, calcium influx via the calcium channel is stimulated. Although the molecular mechanisms underlying these defects are presently unknown, the possibility that they may be related to aberrations in glucose or lipid metabolism are considered. The evidence suggests that classical theories of glucose toxicity, such as excessive polyol production or glycosylation, appear to be insignificant factors in heart. Also insignificant are defects in lipid metabolism leading to accumulation of toxic lipid amphiphiles or triacylglycerol. Rather, the major defects involve membrane changes, such as phosphatidylethanolamine N-methylation and protein phosphorylation, which can be attributed to the state of insulin resistance.
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PMID:Cardiomyopathy associated with noninsulin-dependent diabetes. 166 89

Hypertension results from abnormalities of the control systems that normally regulate blood pressure. These control systems include vascular, cardiogenic, renal, neurogenic, and endocrine mechanisms that interact in a complex but integrated manner to achieve blood pressure homeostasis. Multiple endogenous biologically active substances participate in the regulation of these control systems. Evidence suggests that abnormalities of these regulatory mechanisms resulting from altered genetic and environmental interactions play an important role in the pathogenesis of primary hypertension. Once hypertension develops, it tends to be self-perpetuating via amplifying mechanisms mediated by secondary structural changes in the blood vessels, heart, and kidney. These adaptative structural changes amplify and perpetuate hypertension by increasing systemic vascular resistance, enhancing cardiac output, and impairing renal sodium and water excretion. The long-term sequelae of hypertensive structural changes in these end organs are complications of atherosclerotic vascular disease, cardiac hypertrophy and failure, stroke, and renal failure. With the tools of molecular biology, our understanding of the molecular mechanisms underlying these abnormalities has increased enormously and continues to grow at a rapid pace, as illustrated by the discussion that follows. Our review of the molecular biology of hypertension will address systematically four key areas: 1) molecular biology of the control systems, 2) molecular mechanisms of cardiovascular structural changes, 3) genetics of hypertension, and 4) application of transgenic technology in studies of hypertension.
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PMID:Molecular biology of hypertension. 183 15

In all but a few remote and unacculturated tribes, blood pressure rises with advancing age. By the time Western adult males or females reach their 70s their probability of being hypertensive (BP greater than 140/90 mmHg) exceeds 50%. Unlike various other risk factors for vascular disease, hypertension retains its predictive power as age increases, but since the baseline risk is higher, the number of cases of disease attributable to hypertension is much higher in the elderly than in the young. The reason for the rise in blood pressure with aging is not well established, although a high lifetime intake of sodium may be a contributing factor. It now appears that the major hemodynamic abnormality is an increased peripheral resistance. It is possible that an accentuation of changes that take place with normal aging might be responsible for this phenomenon. They include a reduction in renal function, decreased baroreceptor sensitivity, or increased sympathetic activity. Up until the present time studies have been unable to isolate the mechanisms involved.
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PMID:Hypertension in the elderly: epidemiology and pathophysiology. 200 42

In order to examine the effect of dietary sodium intake on plasma lipids, 15 healthy male volunteers were given a low-salt diet (20 mmol/day) for 3 weeks, adding either placebo, sodium chloride (200 mmol/day), or a non-chloride sodium salt (sodium citrate, 200 mmol Na/day) for one week each, in a single-blind randomized crossover study. Plasma levels of total cholesterol and LDL cholesterol were significantly higher at the end of the placebo period than with either sodium chloride (by 8.7 and 11.9%, respectively) (P less than 0.005) or sodium citrate (by 11.3% and 16.8%, respectively) (P less than 0.005). Thus this effect was dependent on sodium but not on chloride intake. Triglyceride and HDL-cholesterol levels were not affected by the dietary regimens. We conclude that short-term dietary sodium restriction may lead to a rise in plasma total and LDL cholesterol, thereby possibly increasing the risk of atherosclerotic vascular disease. Our findings render it possible that diuretic-induced lipid disturbances may also be caused by sodium depletion.
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PMID:Dietary sodium restriction: adverse effect on plasma lipids. 238 Nov 34

In the present investigation, we analyzed whether sulfated glycosaminoglycans are a common constituent in many different types of amyloid. Serial sections of amyloidotic tissue were stained for the presence of: (a) amyloid by using Congo Red, and (b) glycosaminoglycans by using both the sodium sulfate Alcian blue method and Alcian blue, pH 5.7, with varying concentrations of magnesium chloride. Our results show that sulfated glycosaminoglycans are always associated anatomically with amyloid deposits regardless of the nature of the protein deposited. Sulfated glycosaminoglycans were found in tissues containing AA, AL, inherited cutaneous amyloid, and senile cardiac amyloid (prealbumin). Additionally, we provide evidence that sulfated glycosaminoglycans are closely associated with the amyloid of medullary carcinoma of the thyroid (prothyrocalcitonin), and neuritic plaques, neurofibrillary tangles, and congophilic angiopathy in Alzheimer's disease. It is postulated that these sulfated glycosaminoglycans can influence the folding of diverse proteins such that all forms of amyloid show a significant beta-pleated sheet component.
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PMID:Sulfated glycosaminoglycans: a common constituent of all amyloids? 243 52

We have investigated the hemodynamic actions of iloprost, a stable prostacyclin derivative, in conscious, chronically instrumented rats. Given intravenously by 10-min infusions at doses ranging from 0.0375 to 4 micrograms/min, iloprost lowered mean arterial blood pressure in a dose-dependent and reversible fashion. The effects on blood pressure were accompanied by increases in heart rate (HR); splanchnic nerve activity (SpNA, direct recording); and mesenteric, renal, and hindlimb blood flow (Doppler probes). Doses below the depressor threshold already reduced mesenteric and hindlimb vascular resistance without affecting HR. The reduction of hindlimb resistance outlasted the iloprost infusion period. Chronic sinoaortic deafferentation (SAD) almost abolished the tachycardic reflex responses to intravenous sodium nitroprusside. The reflex increases in SpNA to intravenous iloprost were also largely prevented in SAD animals, but the tachycardic effects of iloprost persisted. In addition, neither beta 1-adrenoceptor blockade alone nor complete cardiac autonomic blockade prevented the heart rate responses to iloprost. Our results show that iloprost is a potent vasodilator that preferentially reduces hindlimb vascular resistance. Low doses of the drug increase regional blood flow without affecting blood pressure or heart rate. The tachycardic effects at higher doses cannot be explained by baroreceptor reflex (BRR) activation alone; they instead suggest a direct action on the heart. The dissociation between vasodilator and depressor effects at low doses may contribute to the therapeutic benefit of the drug in the treatment of vascular disease.
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PMID:Effect of a prostacyclin derivative (iloprost) on regional blood flow, sympathetic nerve activity, and baroreceptor reflex in the conscious rat. 245 Feb 62


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