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

Vascular disease and focal cerebral ischemia still represent the major cause of neurological morbidity and mortality. Mechanisms of hypoxic changes are associated with energy depletion and impairment of biological membranes. Reperfusion after the stroke plays an important role in the development of morphological and functional changes of the nervous tissue. In experiments, different models of focal cerebral ischemia based on the middle cerebral artery occlusion (MCAO) are used. Four main categories of such models are most frequently employed: 1. Temporary intraluminal occlusion of part of the circle of Willis (via internal carotid artery), 2. Abluminal application of the vasoconstrictor peptide (endothelin-1) to the MCA, 3. Tromboembolic models, 4. Microclips. Reliable quantification of morphological changes is also possible. Discussed models are used for testing different types of treatment of the cerebral ischemia, including pharmacological stimulation and blocking of individual membrane receptor systems.
 ...
PMID:[Models of focal hypoxia of the central nervous system]. 863 Oct 55

To evaluate the role of endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide synthesized by endothelial cells, on the endothelial dysfunction in non-insulin-dependent diabetic (type 2) patients, we have measured the circulating ET-1 levels in 25 patients with and without clinically evident vascular complications and in a control group. Circulating ET-1 levels were significantly higher in diabetic patients with angiopathy than in diabetics without angiopathy and in controls (7.02 +/- 2.9 pg/ml vs 4.4 +/- 1.1 pg/ml and 3.08 +/- 0.7 pg/ml, respectively; P < 0.001). No difference was demonstrated between diabetic patients without angiopathy and controls. These findings suggest that ET-1 may be a marker for arterial vascular disease only in patients with overt angiopathy. It is unclear whether it participates in the endothelial injury process or it is merely released from damaged endothelial cells.
 ...
PMID:Angiopathy affects circulating endothelin-1 levels in type 2 diabetic patients. 875 Jul 66

The vascular endothelium regulates the tone of the underlying smooth muscle and the reactivity of blood elements such as platelets and neutrophils by the release of mediators, in particular nitric oxide, prostacyclin and endothelin-1. The first two of these are potent vasodilators which also inhibit platelet and neutrophil aggregation and adhesion, while endothelin-1 is the most potent mammalian vasoconstrictor peptite yet found. There are also interactions between these mediators. For instance, endothelin-1 acts on specific receptors on the endothelium to increase the release of nitric oxide and prostacyclin, while nitric oxide depresses the production and/or release of endothelin-1 from endothelial cells. Endothelin-1 and prostacyclin do not appear to be involved in the basal regulation of blood pressure whereas nitric oxide does for inhibition of its production in normotensive animals produces a marked elevation in blood pressure. Conversely, numerous vascular disease states have been associated with elevations in the production and/or release of endothelin-1 and it has been implicated in the deleterious changes associated with ischaemia/reperfusion injury, subarachnoid haemorrhage and hypertension. Endothelin-1 has also been proposed to be pro-atherogenic, as have reductions in the production of the vasodilator mediators nitric oxide and prostacyclin.
 ...
PMID:Influence of endothelial mediators on the vascular smooth muscle and circulating platelets and blood cells. 880 31

The cardiovascular system is regulated by the central mechanisms, hormones and local vascular mediators. Anatomically, the endothelium lies between smooth muscle cells of the blood vessel wall and the circulating platelets and monocytes. In response to mechanical and humoral signals, endothelial cells release mediators modulating contraction and proliferation of vascular smooth muscle, platelet adhesion and aggregation, coagulation and monocyte adhesion. Nitric oxide (NO), prostacyclin and a putative hyperpolarizing factor mediate relaxation. NO also inhibits smooth muscle migration and proliferation and, together with prostacyclin, platelet adhesion and aggregation. Endothelin-1, thromboxane A2 and prostaglandin H2 are endothelium-derived contracting factors. In contrast to thromboxane A2 and prostaglandin H2 which activate platelets, endothelin-1 has no direct platelet effects, but has proliferative properties in vascular smooth muscle. Under physiological conditions, the endothelium exerts vascular protective effects as it prevents adhesion of blood cells, dilates the vasculature and inhibits vascular smooth muscle proliferation. In disease states, however, endothelial dysfunction mediates vasoconstriction, adhesion of platelets and monocytes and proliferation of vascular smooth muscle cells, all events known to contribute to atherosclerotic vascular disease.
 ...
PMID:The pathogenesis of cardiovascular disease: role of the endothelium as a target and mediator. 882 68

The effects of mycoplasma infection on the biosynthesis of endothelin-1 (ET-1) in cultured human vascular endothelial cell lines were examined to understand regulatory mechanisms of ET-1 biosynthesis and causes of angiopathy due to mycoplasma infection. The growth of normal endothelial cells from the umbilical cord vein and of an immortal endothelial cell line transfected with prepro ET-1 cDNA was decreased, while the secretion of ET-1 into the culture medium was enhanced by mycoplasma infection. However, the rate of ET-1 production in these cell cultures was much higher at the growing phase than at the stationary phase. Immunocytochemical studies with anti-ET-1 antibody and an autoradiographic examination of the labeled nuclei with 3H-TdR revealed that mycoplasma infection induced an elevation of ET-1 production in both S and non-S phase cells. The expression of prepro ET-1 mRNA as examined by in situ hybridization and by RNase protection assay was not altered by mycoplasma infection. Thus, the biosynthesis of ET-1 in vascular endothelial cells may be regulated at the posttranscriptional level.
 ...
PMID:Elevation of endothelin biosynthesis in human endothelial cells with mycoplasma infection. 882 94

Myocardial infarction is the major cause of death in the Western world. Men are more prone to develop coronary artery disease than women, who rarely develop coronary disease before menopause. Although epidemiological data has long been available showing a protective effect of estrogen on the vascular system, the underlying mechanisms have been investigated more thoroughly only in recent years. Meta-analysis studies have revealed that only half of the protective effect on estrogen replacement therapy is due to its positive effects on the lipid profile and that a large part of this protection is caused by mechanisms distinct from lipid metabolism. It is now known that estrogens also exert effects on vascular function and structure of the vessel wall involving numerous cellular and molecular mechanisms. Here we review actions of natural estrogens on human vascular cells and arteries. Estrogens can modulate vascular function by increasing nitric oxide production via stimulation of endothelial nitric oxide synthase (eNOS) and decreasing endothelin-1 levels in vivo. Furthermore, 17 beta-estradiol is an inhibitor of vascular smooth muscle cell proliferation and migration, phenomena that play a major role in atherosclerotic vascular disease and in the remodelling process. 17 beta-estradiol can also acutely affect vascular tone in human arteries and attenuates constriction induced by contractile agonists. Finally, clinical studies have shown that 17 beta-estradiol can acutely and chronically ameliorate vascular function in women with and without vascular disease. In conclusion, results from clinical and in vitro studies confirm the positive effects of natural estrogens on vascular function and protection from coronary heart disease. Thus, primary prevention of coronary heart disease by estrogen replacement therapy after the menopause appears to be a new and straightforward approach by which cardiovascular mortality in women can be reduced.
 ...
PMID:[Action of natural estrogens on the vessel wall: molecular mechanisms and clinical implications]. 896 7

The endothelium is involved in both the physiological regulation of vascular tone and the structural transformation of the vessel under pathological conditions. Under physiological conditions, endothelial cells continuously secrete nitric oxide (NO), which relaxes smooth muscle cells and ensures vessel patency. Damaged or excessively activated endothelial cells can also secrete vasoconstrictor factors, the best known of which is endothelin-1 (ET-1), as well as factors that affect the differentiation and growth of vascular smooth muscle cells. How endothelial cell damage contributes, under pathological conditions, to vascular disease can best be illustrated in patients with diabetes mellitus, in whom there are pronounced changes in endothelial cell structure and function. Endothelial cells also interact with cells in the bloodstream, ET-1 and other factors are released from endothelial cells into the bloodstream, where their chemotactic action can induce leucocytes and platelets to migrate to the endothelial wall. Endothelial cells induce adhesion by expression of specific surface adhesion molecules (selectins, integrins and a supergene family of immunoglobulins) that can interact with ligands on the leucocytes and platelets. The expression of adhesion molecules is increased in endothelial cells chronically damaged by risk factors for atherosclerosis. The disturbed permeability of the endothelial layer in patients with diabetes mellitus and/or hyperlipidaemia leads to an increased influx of substances from the circulation into the vessel wall. In addition, endothelial cell dysfunction can lead to accelerated intravessel blood coagulation. It is evident that the endothelium plays a central role in many of the early pathophysiological processes involved in atherosclerosis. It is therefore important to investigate the effects of antiatherosclerotic therapy on endothelial cell function and cell-to-cell interactions. Until recently, little was known about the direct effects of calcium antagonists on endothelial cell function. Recent studies, including two clinical studies, indicate that calcium antagonists primarily affect interactions of endothelial cells, smooth muscle cells, monocytes and platelets, which play a central role in the early phases of the development of atherosclerosis, whereas the protective effect of these agents on the vascular system appears to be low at later stages.
 ...
PMID:Endothelial function. General considerations. 903 50

Myocardial infarction is the major cause of death in the western world. Men are more prone to develop coronary artery disease than women of the same age, in whom coronary disease is rare before menopause. Epidemiological data have shown that estrogens are vasoprotective--especially in the coronary circulation--but the underlying mechanisms have been investigated more thoroughly only in recent years. Only up to half of the protective effect of estrogen replacement therapy an be attributed to its positive effects of the lipid profile. However, a large part of this protection is caused by mechanisms distinct from lipid metabolism. It is now known that estrogens also exert effects on vascular function and structure of the vessel wall involving numerous cellular and molecular mechanisms. Actions of natural estrogens on human vascular cells and arteries will be discussed. Estrogens modulate vascular function by increasing nitric oxide production via stimulation of endothelial nitric oxide synthase (eNOS) and decreasing endothelin-1 levels in vivo. Furthermore, 17-beta estradiol is a potent inhibitor of vascular smooth muscle cell proliferation and migration, which play a major role in atherosclerotic vascular disease and in the remodeling process. 17-beta estradiol also acutely affects vascular tone in human arteries and attenuates constriction induced by contractile agonists. Finally, clinical studies showed that 17-beta estradiol can acutely and chronically ameliorate vascular function in women with and without vascular disease. In conclusion, results from clinical and in vitro studies showed positive effects of natural estrogens on vascular function which could explain in part their protective actions against coronary heart disease. Thus, primary prevention of coronary heart disease by estrogen replacement therapy after menopause appears to be a new approach to reduce cardiovascular mortality in women.
 ...
PMID:[Vascular protection with estrogen. In-vitro and in-vivo effects--mechanisms and clinical implication]. 906 30

Plasma endothelin-1 was measured around the clock in 72 subjects. Cosinor methods were used to assess circadian and other recurrent variation and trends, that is, the time structure (chronome) of this peptide. Multifactorial analyses of variance and linear regressions assessed chronome alterations associated with different risk factors: diabetes, obesity, high cholesterol, high blood pressure, vascular disease, smoking, and age. The rhythm-adjusted mean (MESOR) of endothelin-1 is elevated in diabetes and vascular disease. Diabetes is also associated with a larger circadian amplitude. A circadian variation in a subgroup of low-risk subjects is modulated by components with both lower and higher frequency.
 ...
PMID:Endothelin-1's chronome indicates diabetic and vascular disease chronorisk. 911 61

Endothelins are ubiquitously produced 21-amino-acid peptides that were discovered as an endothelial product and may play important roles in cardiovescular physiology and pathophysiology. The main endothelin produced by the endothelium is endothelin-1. The vasoconstrictor role of endothelins may participate in blood pressure elevation and vascular hypertrophy in salt-dependent models of hypertension (deoxycorticosterone acetate-salt hypertensive rats, spontaneously hypertensive rats treated with deoxycorticosterone, acetate and salt, and Dehl salt-sensitive rats), and in stroke-prone spontaneously hypertensive rats. In humans, endothelins may play important roles in moderate to severe essential hypertension, and in the hypertension of African-Americans. Endothelins may be involved in cardiac hypertrophy, and there is increasing evidence of their participation in heart failure, in which acute endothelin antagonism in humans exerts beneficial effects. Endothelin expression is enhanced in smooth muscle cells migrating into the intima of arteries in atherosclerosis, suggesting a role in atherogenesis. Endothelin may participate as a vasoconstrictor in coronary artery disease, and as a contributor to intimal proliferation in restenosis after coronary angioplasty. In patients with myocardial infarction, cardiac production of endothelin is increased, particularly in those with cardiogenic shock. There is a potential for participation of endothelins in vasospasm accompanying stroke or subarachnoid hemorrhage: in the latter, endothelin antagonism has shown beneficial effects in experimental models. In neonatal and in primary pulmonary hypertension, endothelin expression is enhanced, and in experimental models endothelin antagonism resulted in favorable responses. Systemic sclerosis is another, peripheral, form of vascular disease in which endothelin may play a role and in which endothelin antagonism may be an interesting therapeutic alternative. The pathophysiologic role of endothelins is becoming increasingly apparent in cardiovascular disease, generating interesting potential therapeutic targets for the use of endothelin antagonists or endothelin-converting enzyme inhibitors.
 ...
PMID:Clinical significance of endothelin in cardiovascular disease. 926 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>