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)

Administration of rat renin to uninephrectomized rats reproduced most, if not all, the changes (hypertension, vascular disease, hypertrophy of the zona glomerulosa of the adrenals) found after partial constriction of the renal artery. This is taken as evidence that the renal pressor system plays a major role in the pathogenesis of renal hypertension.
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PMID:HYPERTENSIVE VASCULAR DISEASE PRODUCED BY HOMOLOGOUS RENIN. 1417 62

Supravalvular aortic stenosis is an autosomal-dominant disease of elastin (Eln) insufficiency caused by loss-of-function mutations or gene deletion. Recently, we have modeled this disease in mice (Eln+/-) and found that Eln haploinsufficiency results in unexpected changes in cardiovascular hemodynamics and arterial wall structure. Eln+/- animals were found to be stably hypertensive from birth, with a mean arterial pressure 25-30 mmHg higher than their wild-type counterparts. The animals have only moderate cardiac hypertrophy and live a normal life span with no overt signs of degenerative vascular disease. Examination of arterial mechanical properties showed that the inner diameters of Eln+/- arteries were generally smaller than wild-type arteries at any given intravascular pressure. Because the Eln+/- mouse is hypertensive, however, the effective arterial working diameter is comparable to that of the normotensive wild-type animal. Physiological studies indicate a role for the renin-angiotensin system in maintaining the hypertensive state. The association of hypertension with elastin haploinsufficiency in humans and mice strongly suggests that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension.
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PMID:Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency. 1459 55

Obstructive sleep apnoea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension. Although the association between OSA and the metabolic syndrome tends to confound studies of the independent effects of OSA on vascular disease, recent evidences from basic science to epidemiological and clinical studies suggest that OSA may add worsening pathophysiological conditions to obesity. OSA contributes to the imbalance between vasodilators and vasoconstrictors, in particular through oxidative stress-dependent catabolism of nitric oxide, increased sympathetic nerve activity, enhanced renin-angiotensin system activity and endothelin synthesis. Additionally, several recent studies suggest that OSA may be a circumstance favouring central and vascular resistance to leptin. The beneficial effects of this hormone in normal subjects, are lost during endothelial dysfunction and OSA. Moreover, high leptin concentrations, within a range observed during OSA, display adverse effects on endothelial function and vascular physiology. Through of a yet unknown mechanism, OSA per se accounts for part of the elevated serum leptin concentration reported in patients. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnoea and the ensuing acute hemodynamic changes during sleep. Accordingly, vasopressor mediators and leptin concentration are shifted toward normal values by CPAP. Thus, in addition to this effective therapy, evaluation of specific strategies targeting leptin sensitivity and vasopressor mediators may open novel perspectives for treatment of OSA and its associated end-organ damages.
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PMID:[Effect of sleep apnea syndrome on the vascular endothelium]. 1464 10

Clinical and experimental evidence suggests that the pathways by which hypertension and dyslipidemia lead to vascular disease may overlap and that angiotensin II (Ang II) is involved in restructuring of the arterial wall in both atherosclerosis and hypertension. Ang II represents a potent proinflammatory agent promoting recruitment of monocytes into the vascular intima. Ang II also indirectly facilitates transformation of macrophages and smooth muscle cells into foam cells by promoting superoxide radical formation (via NADP/NADPH oxidase stimulation). The oxidative stress produced by Ang II leads to enhanced low-density lipoprotein oxidation and degradation of nitric oxide, an important vascular protective molecule capable of retarding atherosclerosis progression. The importance of the renin-angiotensin system (RAS) in atherogenesis is highlighted by studies in animal models as well as human beings indicating that inhibition of angiotensin-converting enzyme or blockade of type 1 Ang II receptors retards the development of atherosclerotic lesions. In light of a causal and central role of Ang II in atherogenesis, blockade of the RAS represents an important therapeutic consideration in the prevention and treatment of atherosclerotic disease.
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PMID:Renin-angiotensin system as a therapeutic target in managing atherosclerosis. 1470 95

The hemorphins are a family of opioid receptor-binding peptides originating from the beta-chain of hemoglobin and have been found at high levels within the central and peripheral nervous systems. In addition to opioid receptor binding, hemorphins have been shown to have a number of effects on the renin-angiotensin system, including inhibition of angiotensin-converting enzyme and angiotensin IV receptor binding. However, relatively few studies have examined the role of hemorphins in neurological diseases. Here we report the first study of hemorphins in Alzheimer's disease (AD) brains. Quantitative MALDI-TOF mass spectrometry was employed to assess levels of LVV and VV hemorphin-6 and -7 in 10 control and 10 AD brain tissue samples. LVV hemorphin-6 and total hemorphin levels were elevated in AD temporal neocortex but not in hippocampus, occipital lobe, or frontal lobe. The elevation of hemorphins is probably indicative of a vascular abnormality resulting from cerebral amyloid angiopathy associated with both neurodegenerative disease and aging.
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PMID:Quantification of hemorphins in Alzheimer's disease brains. 1499 46

The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has significantly reduced morbidity and mortality across the continuum of vascular disease. The utilization of these agents, however, remains suboptimal. The drugs are not prescribed in many patients because of concerns regarding their effects on renal function. Despite overwhelming evidence in favor of renoprotection, it is not uncommon for the glomerular filtration rate (GFR) to decrease shortly after starting treatment with an ACE inhibitor or ARB. This response is functional in nature and should be expected based on renal physiology and its dependence on the renin-angiotensin system to maintain GFR. Unfortunately, this phenomenon sometimes is viewed as an adverse effect or an indicator of underlying pathology. Although somewhat counterintuitive, early elevations in serum creatinine concentration are associated with improved long-term renal outcomes in patients with renal insufficiency and thus support, rather than condemn, continued treatment. Clinicians should be aware of the physiologic course associated with blockade of the renin-angiotensin system so that these agents will not be withheld unnecessarily.
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PMID:Elevations in serum creatinine concentration: concerning or reassuring? 1452 53

Low-salt diets have potential for prevention and treatment of hypertension, and may also reduce risk for stroke, left ventricular hypertrophy, osteoporosis, renal stones, asthma, cataract, gastric pathology, and possibly even senile dementia. Nonetheless, the fact that salt restriction evokes certain counter-regulatory metabolic responses-- increased production of renin and angiotensin II, as well as increased sympathetic activity--that are potentially inimical to vascular health, has suggested to some observers that salt restriction might not be of unalloyed benefit, and might in fact be contraindicated in some "salt-resistant" subjects. Current epidemiology indicates that lower-salt diets tend to reduce coronary risk quite markedly in obese subjects, whereas the impact of such diets on leaner subjects (who are less likely to be salt sensitive) is equivocal--seemingly consistent with the possibility that salt restriction can exert countervailing effects on vascular health. There is considerable evidence that sodium chloride, rather than sodium per se, is responsible for the known adverse effects of dietary salt. Other non-halide sodium salts, such as sodium citrate or bicarbonate, do not raise plasma volume, increase blood pressure, boost urinary calcium loss, or promote stroke in stroke-prone rats. Nonetheless, these compounds have been shown to blunt the impact of salt restriction on renin, angiotensin II, and sympathetic activity in humans. This may rationalize limited clinical evidence that organic sodium salts can decrease blood pressure in salt-restricted hypertensives. Furthermore, organic sodium salts have an alkalinizing metabolic impact favorable to bone health. These considerations suggest that restricting dietary salt to the extent feasible, while encouraging consumption of organic sodium salts in mineral waters, soft drinks, or other nutraceuticals--preferably in conjunction with organic potassium salts and taurine--may represent a superior strategy for controlling blood pressure, promoting vascular health, and preserving bone density. Further clinical studies should determine whether a moderately salt-restricted diet supplemented with organic sodium salts has a better and more uniform impact on hypertension than salt restriction alone, while rodent studies should examine the comparative impact of these regimens on rodents prone to vascular disease.
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PMID:Should we restrict chloride rather than sodium? 1519 67

Albuminuria is recognized in all hypertension guideline statements as a cardiovascular risk factor and indicator of kidney disease. Recent data also demonstrate a strong association between the presence of microalbuminuria and elevations in C-reactive protein. Thus, the increased membrane permeability that generates microalbuminuria may be secondary to an inflammatory process. Progression from microalbuminuria (>30 and < or =300 mg albumin/g creatinine) to macroalbuminuria (>300 mg albumin/g creatinine) indicates a worsening of vascular disease and the presence of kidney disease. Recent outcome trials of kidney disease progression have demonstrated the best results among those with reductions in albuminuria in concert with blood pressure (BP) reduction. Thus, use antihypertensive agents that not only lower BP but also lower or normalize albuminuria levels. All recent guideline statements support the use of agents that block the renin-angiotensin-aldosterone system as part of a regimen to achieve the BP goal. Further lowering of albuminuria may be achieved by adding either a nondihydropyridine calcium antagonist such as verapamil or diltiazem, or aldosterone receptor blockers. Use of an angiotensin receptor blocker added to an angiotensin-converting enzyme inhibitor or vice versa can further lower albuminuria by an additional 30%-40%, which is not true of the additional lowering of BP.
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PMID:Implications of albuminuria on kidney disease progression. 1553 7

Recent experimental findings have led to renewed interest in the possible role of uric acid in the pathogenesis of both hypertension and vascular disease. Often considered an antioxidant, biochemical and in vitro data indicate that noncrystalline, soluble uric acid also can react to form radicals, increase lipid oxidation, and induce various pro-oxidant effects in vascular cells. In vitro and in vivo findings suggest that uric acid may contribute to endothelial dysfunction by inducing antiproliferative effects on endothelium and impairing nitric oxide production. Proinflammatory and proliferative effects of soluble uric acid have been described on vascular smooth muscle cells (VSMCs), and in animal models of mild hyperuricemia, hypertension develops in association with intrarenal vascular disease. Possible adverse effects of uric acid on the vasculature have been linked to increased chemokine and cytokine expression, induction of the renin-angiotensin system, and to increased vascular C-reactive protein (CRP) expression. Experimental evidence suggests a complex but potentially direct causal role for uric acid in the pathogenesis of hypertension and atherosclerosis.
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PMID:Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. 1566 Mar 33

Although hyperuricemia has long been associated with renal disease, uric acid has not been considered as a true mediator of progression of renal disease. The observation that hyperuricemia commonly is associated with other risk factors of cardiovascular and renal disease, especially hypertension, has made it difficult to dissect the effect of uric acid itself. However, recent epidemiologic evidence suggests a significant and independent association between the level of serum uric acid and renal disease progression with beneficial effect of decreasing uric acid levels. Furthermore, our experimental data using hyperuricemic animals and cultured cells have provided robust evidence regarding the role of uric acid on progression of renal disease. Hyperuricemia increased systemic blood pressure, proteinuria, renal dysfunction, vascular disease, and progressive renal scarring in rats. Recent data also suggest hyperuricemia may be one of the key and previously unknown mechanisms for the activation of the renin-angiotensin and cyclooxygenase-2 (COX-2) systems in progressive renal disease. Although we must be cautious in the interpretation of animal models to human disease, these studies provide a mechanism to explain epidemiologic data that show uric acid is an independent risk factor for renal progression. Although there is no concrete evidence yet that uric acid bears a causal or reversible relationship to progressive renal disease in humans, it is time to reevaluate the implication of hyperuricemia as an important player for progression of renal disease and to try to find safe and reasonable therapeutic modalities in individual patients based on their clinical data, medication history, and the presence of cardiovascular complications.
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PMID:Uric acid and chronic renal disease: possible implication of hyperuricemia on progression of renal disease. 1566 Mar 34


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