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)

Cardiovascular disease is the number one cause of death in the United States. Vascular smooth muscle cells (VSMC) are an important constituent of the vessel wall that can bring about pathological changes leading to vascular disease. Depending on the environment, the function of VSMC can deviate profoundly from its normal contractile role. Despite advances in research, the underlying mechanisms that activate VSMC toward vascular disease are poorly understood. For the first time, we have observed that factor XII and high-molecular-weight kininogen, constituents of the blood plasma, can bind to VSMC in a Zn2+-dependent manner. In the presence of prekallikrein, this assembly of factor XII and high-molecular-weight kininogen on VSMC leads to the activation of prekallikrein to kallikrein with a rapid formation of bradykinin. The amount of bradykinin in the culture medium then decreases, presumably because of the presence of a kininase activity. p44/42 mitogen-activated protein kinase is rapidly phosphorylated in response to in situ-generated or in vitro-added bradykinin and is inhibited by bradykinin antagonist HOE-140. Binding of factor XII to VSMC also results in a concentration-dependent phosphorylation of p44/42 mitogen-activated protein kinase. This early mitogenic signal, which is also implicated in atherogenesis, may change the metabolic and proliferative activity of VSMC, which are key steps in the progression of atherosclerosis.
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PMID:Assembly, activation, and signaling by kinin-forming proteins on human vascular smooth muscle cells. 1596 76

To determine the relationship of arsenic, copper, cadmium, manganese, lead, zinc and selenium to Blackfoot disease (BFD, a peripheral vascular disorder endemic to areas of Taiwan, which has been linked to arsenic in drinking water) the authors measured the amount of these substances in urine from BFD patients, using atomic absorption spectrometry. Results indicate significantly higher amounts of urinary arsenic, copper, cadmium, manganese, and lead for BFD patients than for normal controls, also significantly lower urinary zinc and selenium.
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PMID:Determination of urinary trace elements (arsenic, copper, cadmium, manganese, lead, zinc, selenium) in patients with Blackfoot disease. 1678 78

ROS are a risk factor of several cardiovascular disorders and interfere with NO/soluble guanylyl cyclase/cyclic GMP (NO/sGC/cGMP) signaling through scavenging of NO and formation of the strong oxidant peroxynitrite. Increased oxidative stress affects the heme-containing NO receptor sGC by both decreasing its expression levels and impairing NO-induced activation, making vasodilator therapy with NO donors less effective. Here we show in vivo that oxidative stress and related vascular disease states, including human diabetes mellitus, led to an sGC that was indistinguishable from the in vitro oxidized/heme-free enzyme. This sGC variant represents what we believe to be a novel cGMP signaling entity that is unresponsive to NO and prone to degradation. Whereas high-affinity ligands for the unoccupied heme pocket of sGC such as zinc-protoporphyrin IX and the novel NO-independent sGC activator 4-[((4-carboxybutyl){2-[(4-phenethylbenzyl)oxy]phenethyl}amino) methyl [benzoic]acid (BAY 58-2667) stabilized the enzyme, only the latter activated the NO-insensitive sGC variant. Importantly, in isolated cells, in blood vessels, and in vivo, BAY 58-2667 was more effective and potentiated under pathophysiological and oxidative stress conditions. This therapeutic principle preferentially dilates diseased versus normal blood vessels and may have far-reaching implications for the currently investigated clinical use of BAY 58-2667 as a unique diagnostic tool and highly innovative vascular therapy.
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PMID:Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. 1695 36

The SU.VI.MAX study is a double blind, randomized, placebo-controlled trial testing, for 7,5 years, the effect of a combination of antioxidant vitamins and minerals, at doses considered to be nutritional (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium and 20 mg zinc) in reducing cancer and ischemic vascular disease incidence in a general population (12.741 middle-aged). After 7.5 years, low-dose antioxidant supplementation had no effect on vascular disease incidence. This dose lowered, however, total cancer incidence in men, but not in women. With regard to contradictory results of observational and interventional studies published for the last decades, we can consider that the effect of antioxidants on cancer may depend on the doses (nutritional versus pharmacological), baseline antioxidant status (different between gender and/or nutritional status) and health status of subjects (healthy versus cancer high-risk subjects). Antioxidant supplementation may have a beneficial effect on cancer incidence only in healthy subjects who are not exposed to cancer risk, and with a particularly low baseline status. Finally, antioxidants as well as free radicals appear to be ambiguous nutrients with a wide range of benefits and toxicity. High doses of antioxidant supplements may be deleterious in high-risk subjects without any clinical symptoms in whom the initial phase of cancer development has already started.
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PMID:[The SU.VI.MAX study, a randomized, placebo-controlled trial on the effects of antioxidant vitamins and minerals on health]. 1711 69

Mercury, cadmium, and other heavy metals have a high affinity for sulfhydryl (-SH) groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (NAC, ALA, GSH), with subsequent decreased oxidant defense and increased oxidative stress. Both bind to metallothionein and substitute for zinc, copper, and other trace metals reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in ATP, depletion of glutathione, and increased lipid peroxidation; increased oxidative stress is common. Selenium antagonizes mercury toxicity. The overall vascular effects of mercury include oxidative stress, inflammation, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, immune dysfunction, and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, CHD, MI, increased carotid IMT and obstruction, CVA, generalized atherosclerosis, and renal dysfunction with proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury, cadmium, and other heavy metals inactivate COMT, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to heavy metal toxicity. Cadmium concentrates in the kidney, particularly inducing proteinuria and renal dysfunction; it is associated with hypertension, but less so with CHD. Renal cadmium reduces CYP4A11 and PPARs, which may be related to hypertension, sodium retention, glucose intolerance, dyslipidemia, and zinc deficiency. Dietary calcium may mitigate some of the toxicity of cadmium. Heavy metal toxicity, especially mercury and cadmium, should be evaluated in any patient with hypertension, CHD, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, serum, etc. with baseline and provoked evaluation should be done.
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PMID:The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. 1740 90

The aim of this study was to discuss the serum copper (Cu), zinc (Zn), nitric oxide (NO), glutathione (GSH), advanced oxidation protein products (AOPP) levels, and superoxide dismutase (SOD) activities with diabetic retinopathy severity. Twenty-five patients with proliferative diabetic retinopathy (PDR group 1), 25 patients with nonproliferative diabetic retinopathy (NPDR group 2), and 25 nondiabetic controls (control group) were included in the study. Patients who had macrovascular complications of diabetes (coronary arterial disease, periferic vascular disease) were excluded. The major finding of our study was that we did not observe any differences between group 1 and 2, which we aimed to discuss the severity of diabetic retinopathy. As the levels of SOD and Zn were not different between the groups, statistically significant differences were observed for GSH, NO, and Cu levels when compared to control group. AOPP levels were statistically increased in group 1 compared to control group. It can be suggested that hyperglycemia in DM is associated with accelerated nonenzymatic glycation and oxidative stress.
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PMID:Antioxidant enzymes and diabetic retinopathy. 1746 Jan 79

Oxidative stress is one of the main causes of vascular disease. This study aims to investigate the antioxidant activity exerted by zinc in primary rat endothelial cells (EC). Using a 24-h treatment with hydrogen peroxide as a model for oxidative stress, we found that zinc supplementation protects from peroxide-induced cell death via increasing the transcription of the catalytic subunit (heavy chain) of glutamate-cysteine ligase (GCLC) and the concentrations of glutathione (GSH). Conversely, zinc depletion significantly decreased the expression of GCLC and the cellular GSH levels, resulting in an increased susceptibility of EC to oxidative stress. Using confocal microscopy and the RNA silencing technique, we found that zinc upregulates the expression of GCLC by activating the transcription factor Nrf2. Surprisingly, the intracellular zinc sensor, metal-responsive transcription factor-1, is not involved in the zinc-induced expression of GCLC. The present study shows that zinc controls the redox state of EC by regulating the de novo synthesis of GSH. This molecular mechanism may contribute to the elaboration of new nutritional and/or pharmaceutical approaches for protecting the endothelium against oxidative stress.
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PMID:Zinc protects endothelial cells from hydrogen peroxide via Nrf2-dependent stimulation of glutathione biosynthesis. 1835 58

The content of total flavone in carthmus tinctorius L in Xinjiang was determined by ultraviolet spectrophotometry with scan from 200 to 400 nm where the maximum absorption wavelength was 267.00 nm. The contents of ten trace elements and constant elements in carthmus tinctorius L including potassium, sodium, calcium, magnesium, iron, chromium, nickel, manganese, copper and zinc were determined by flame atomic absorption spectrophotometry. The results showed that there were comparatively rich trace elements and high total flavone, among which are comparatively high calcium, magnesium, chromium, copper and zinc in carthmus tinctorius L. It provided useful data for discussing the relationship between the content of total flavone and the trace elements in carthmus tinctorius L, and for studing the relationship between the trace elements in carthmus tinctorius L and the cure for cardio-cerebral vascular disease.
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PMID:[Analysis and study of total flavone and trace element in carthmus tinctorius L]. 1842 59

An endemic peripheral vascular disorder resulting in gangrene of the lower extremities, especially of the feet, is called 'Blackfoot disease (BFD)'. Clinically, the symptoms and signs of Blackfoot disease are similar to those of Buerger's disease. In this study, the objective is to examine the amount of arsenic, mercury, zinc, lead, and selenium in urine samples from BFD patients. After pre-treatment with acids, the samples were digested by means of a microwave oven. The determination of arsenic mercury, zinc, lead and selenium were by hydride atomic absorption spectrometry (HAAS), cold vapor atomic absorption spectrometry (CVAAS), flame atomic absorption spectrometry (FAAS), graphite furnace absorption spectrometry (GFAAS), respectively. The results indicated that urinary arsenic, mercury and lead of the BFD patients were significantly higher than those of the normal controls, while urinary zinc and selenium were significantly lower than those of the normal controls. The possibility that these elements are involved in the etiology of diseases is discussed.
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PMID:Determination of urinary trace elements (As, Hg, Zn, Pb, Se) in patients with Blackfoot disease. 1896 82

Oxidative stress may cause endothelial dysfunction and vascular disease. It has been shown that NO protects endothelial cells (EC) against H(2)O(2)-induced toxicity. In addition, it is known that NO within cells induces a zinc release from proteins containing zinc-sulfur complexes. The aim of this study was to investigate whether zinc released intracellularly by NO plays a signaling role in the NO-mediated protection against H(2)O(2) in rat aortic EC. Our results show that the NO-mediated protection toward H(2)O(2) depends on the activities of glutathione peroxidase and glutamate cysteine ligase (GCL), the rate-limiting enzyme of glutathione (GSH) de novo biosynthesis. Moreover, NO increases the synthesis of the antioxidant GSH by inducing the expression of the catalytic subunit of GCL (GCLC). Chelating intracellular "free" zinc abrogates the NO-mediated increase of GCLC and of cellular GSH levels. As a consequence, the NO-mediated protection against H(2)O(2)-induced toxicity is impaired. We also show that under proinflammatory conditions, both cellular NO synthesis and intracellular "free" zinc are required to maintain the cellular GSH levels. Using RNA interference and laser scanning microscopy, we found that the NO-induced expression of GCLC depends on the activation of the transcription factor Nrf2 but not on the activity of the "zinc-sensing" transcription factor MTF-1. These findings show that intracellular "free" zinc plays a signaling role in the protective activity of NO and could explain why maintenance of an adequate zinc status in the endothelium is important to protect from oxidative stress and the development of vascular disease.
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PMID:Nitric oxide-mediated protection of endothelial cells from hydrogen peroxide is mediated by intracellular zinc and glutathione. 1919 64


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