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)

Hemodialysis (HD) patients are commonly affected by secondary hyperparathyroidism (SHPT), in which 3 well-known factors are usually involved: hypocalcemia, hyperphosphatemia and calcitriol deficiency. Classically, high parathyroid hormone (PTH) levels cause bone-associated diseases, such as osteitis fibrosa and renal osteodystrophy, but more recently it has been demonstrated the link between SHPT and a systemic toxicity, with a major role in determining cardio-vascular disease, including arterial calcification, endocrine disturbances, compromised immune system, neurobehavioral changes, and altered erythropoiesis. Treatment with calcitriol (CT), the active form of vitamin D, reduces parathyroid hormone (PTH) levels, but may result in elevations in serum calcium (Ca) and phosphorus (P), increasing the risk of cardio-vascular calcification in the HD population. Several new vitamin D analogs have been developed and investigated with the rationale to treat SHPT with a reduced risk of hypercalcemia and hyperphosphatemia in HD patients. Paricalcitol (1,25-dihydroxy-19-nor-vitamin D(2), 19-Nor-D(2)) is a vitamin D analog that suppresses PTH secretion with minimal increases on serum calcium and phosphate levels. It was demonstrated that paricalcitol prevents vascular calcification in experimental models of renal failure, compared with calcitriol. Furthermore, 19-Nor-D(2) is the first analog approved for use in HD patients and is available for i.v. and oral administration, commonly 3 times weekly after HD. The purpose of the present review is to analyze the pathogenesis and treatment of SHPT in HD patients, and the role of paricalcitol in the prevention of arterial calcification.
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PMID:Pathogenesis and treatment of secondary hyperparathyroidism in dialysis patients: the role of paricalcitol. 1839 17

Depression is associated with vascular disease, such as myocardial infarction and stroke. Pharmacological treatments may contribute to this association. On the other hand, Mg(2+) deficiency is also known to be a risk factor for the same category of diseases. In the present study, we examined the effect of imipramine on Mg(2+) homeostasis in vascular smooth muscle, especially via melastatin-type transient receptor potential (TRPM)-like Mg(2+) -permeable channels. The intracellular free Mg(2+) concentration ([Mg(2+) ](i) ) was measured using (31) P-nuclear magnetic resonance (NMR) in porcine carotid arteries that express both TRPM6 and TRPM7, the latter being predominant. pH(i) and intracellular phosphorus compounds were simultaneously monitored. To rule out Na(+) -dependent Mg(2+) transport, and to facilitate the activity of Mg(2+) -permeable channels, experiments were carried out in the absence of Na(+) and Ca(2+) . Changing the extracellular Mg(2+) concentration to 0 and 6 mM significantly decreased and increased [Mg(2+) ](i) , respectively, in a time-dependent manner. Imipramine statistically significantly attenuated both of the bi-directional [Mg(2+) ](i) changes under the Na(+) - and Ca(2+) -free conditions. This inhibitory effect was comparable in influx, and much more potent in efflux to that of 2-aminoethoxydiphenyl borate, a well-known blocker of TRPM7, a channel that plays a major role in cellular Mg(2+) homeostasis. Neither [ATP](i) nor pH(i) correlated with changes in [Mg(2+) ](i) . The results indicate that imipramine suppresses Mg(2+) -permeable channels presumably through a direct effect on the channel domain. This inhibitory effect appears to contribute, at least partially, to the link between antidepressants and the risk of vascular diseases.
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PMID:Imipramine inhibition of TRPM-like plasmalemmal Mg2+ transport in vascular smooth muscle cells. 2013 12

Oxidative stress and vascular calcifications are emergent risk factors for the accelerated atherosclerosis process featuring chronic kidney disease (CKD). Vascular calcification is an active process similar to bone modelling, where BMP-2 may play a pathogenic role. Aim of our study was to investigate the link between oxidative stress, BMP-2 protein expression and vascular disease in CKD. We enrolled 85 CKD patients (K-DOQI stage II or higher) and 41 healthy individuals. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) was used as a marker of oxidative stress. Brachial-ankle pulse wave velocity (baPWV) was used as a measure of arterial stiffness. BMP-2 serum levels were significantly higher in CKD patients than in controls (p<0.0001). Serum 8-OHdG levels were significantly higher in CKD patients compared to controls (p<0.05). BMP-2 serum levels were inversely associated with eGFR (r=-0.3; p=0.01) and directly correlated with 8-OHdG serum concentrations (r=-0.3; p=0.03). Arterial stiffness was inversely correlated with eGFR (r=-0.4; p=0.001) and directly correlated with BMP-2 (r=0.3; p=0.03), 8-OHdG (r=0.4, p=0.02) and phosphorus serum levels (r=0.3; p=0.007). In a multiple regression model, phosphorus and BMP-2 were independently correlated with baPWV. In vitro exposure to H(2)O(2) induced a time and dose-dependent increase in BMP-2 expression in an immortalized endothelial cell line. Moreover, H(2)O(2) pre-incubation of cultured vascular smooth muscle cell enhanced the BMP-2-induced up-regulation of ALPL, an osteoblastic phenotype marker. Our data suggest that in CKD BMP-2 may represent the molecular link between oxidative stress and arterial stiffness due to vascular calcification.
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PMID:Bone morphogenetic protein-2 may represent the molecular link between oxidative stress and vascular stiffness in chronic kidney disease. 2053 31

Cardiovascular disease is the leading cause of death in both chronic kidney disease and peritoneal dialysis/hemodialysis patients. Vascular disease prevention in these patients is therefore important to reduce the incidence of cardiovascular events and the high morbidity and mortality. This Editorial discusses the traditional, (1) smoking, (2) dyslipidemia, (3) body mass index, (4) glycemic control and (5) blood pressure, and non-traditional, (1) anemia, (2) vitamin D/hyperparathyroidism, (3) calcium/phosphorus metabolism and (4) magnesium, risk factors in renal patients. Current evidence does not support routine statin use and antiplatelet medication to dialysis patients. Patient compliance and adherence to proposed measures could be essential to reduce cardiovascular events and mortality rates in this high-risk population.
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PMID:Cardiovascular events in chronic dialysis patients: emphasizing the importance of vascular disease prevention. 2057 91

Chronic cerebral hypoperfusion and aging can be related to vascular dementia manifested by the decline in cognitive abilities and memory impairment. The identification of specific biomarkers of vascular disorder in early stages is important for the development of neuroprotective agents. In the present study, a three-vessel occlusion (3-VO) rat model of vascular dementia in the middle-aged rat brain was used to investigate the effect of global cerebral hypoperfusion. A multimodal study was performed using magnetic resonance spectroscopy, MR-microimaging, histology and behavioral tests. Our measurements showed a signal alteration in T2-weighted MR images, the elevation of T2 relaxation times and histologically proven neural cell death in the hippocampal area, as well as mild changes in concentration of proton and phosphorus metabolites. These changes were accompanied by mild behavioral alterations in the open field and slightly decreased habituation. The analysis of the effects of vascular pathology on cognitive functions and neurodegeneration can contribute to the development of new treatment strategies for early stages of neurodegeneration.
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PMID:Pathophysiological rat model of vascular dementia: magnetic resonance spectroscopy, microimaging and behavioral study. 2479 9

Elevated serum phosphorus levels are common in patients with chronic kidney disease and are associated with heart and vascular disease, conditions that in turn are associated with increased mortality. Accurately managing phosphorus intake by restricting dietary protein alone can prove challenging because protein from different sources can contain varying amounts of available phosphorus. Additives used in processed foods frequently are high in inorganic phosphorus, which is readily absorbed, compounding this difficulty. Recent evidence suggests that dietary protein restriction in some cases may do more harm than good in some patients treated with maintenance hemodialysis because protein restriction can lead to protein-energy wasting, which is associated with increased mortality. Accordingly, phosphorus binders are important for managing hyperphosphatemia in dialysis patients. Managing hyperphosphatemia in patients with late-stage chronic kidney disease requires an individualized approach, involving a combination of adequate dietary advice, phosphate-binder use, and adjustments to dialysis prescription. We speculate that increased use of phosphate binders could allow patients to eat more protein-rich foods and that communicating this to patients might increase their perception of their need for phosphate binders, providing an incentive to improve adherence. The aim of this review is to discuss the challenges involved in maintaining adequate nutrition while controlling phosphorus levels in patients on maintenance hemodialysis therapy.
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PMID:Balancing nutrition and serum phosphorus in maintenance dialysis. 2481 75

Experimental and clinical studies aimed at investigating the mechanism(s) underlying vascular complications of diabetes indicate that a great number of molecules are involved in the pathogenesis of these complications. Most of these molecules are inflammatory mediators or markers generated by immune or adipose tissue. Some of them, i.e. resistin and sortilin, have been shown to be involved in the cross talk between adipocytes and inflammatory cells. This interaction is an attractive area of research, particularly in type 2 diabetes and obesity. Other proteins, such as adiponectin and visfatin, appear to be more promising as possible vascular markers. In addition, some molecules involved in calcium/phosphorus metabolism, such as klotho and FGF23, have an involvement in the pathogenesis of diabetic vasculopathy, which appears to be dependent on the degree of vascular impairment. Inflammatory markers are a promising tool for treatment decisions while measuring plasma levels of adipokines, sortilin, Klotho and FGF23 in adequately sized longitudinal studies is expected to allow a more precise characterization of diabetic vascular disease and the optimal use of personalized treatment strategies.
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PMID:Biomarkers of vascular disease in diabetes: the adipose-immune system cross talk. 3191 81


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