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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The pathogenesis of cardiovascular disease: role of the endothelium as a target and mediator. 882 68

Endothelial injury is a central feature of vascular disease induced by cigarette smoking and may act as a precursor for future atherosclerosis. Using forearm occlusion plethysmography, we studied the vascular responses to methacholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) infused into the brachial artery of 35 long-term cigarette smokers and 16 nonsmoking subjects. NG-monomethyl-L-arginine (L-NMMA), a stereospecific inhibitor of nitric oxide production, was used to inhibit synthesis of nitric oxide in the endothelium. The reactive hyperemic response at peak and during recovery to the temporary interruption of forearm blood flow was also compared between groups. Smokers had elevated carboxyhemoglobin levels compared with nonsmokers (5.1 +/- 2.1% vs 0.8 +/- 0.4%; p < 0.001). No differences were found in the peak or late hyperemic responses between groups. In smokers, the incremental infusions of methacholine and sodium nitroprusside increased forearm blood flow from 3.6 +/- 1.2 to 12.9 +/- 9.0 ml.min-1 x 100 ml-1 and from 4.0 +/- 1.5 to 9.3 +/- 4.0 ml.min-1 x 100 ml-1, respectively, compared with 3.2 +/- 1.0 to 13.5 +/- 5.6 ml.min-1 x 100 mL-1 and from 2.9 +/- 0.7 to 8.6 +/- 4.2 ml.min-1 x 100 ml-1 in nonsmoking subjects (p = NS). L-NMMA (4 mumol/min for 5 minutes) significantly reduced forearm blood flow in both smokers and nonsmokers from 4.1 +/- 1.4 to 3.4 +/- 1.2 ml.min-1 x 100 ml-1 and 3.8 +/- 0.7 to 2.3 +/- 0.5 mL.min-1 x 100 ml-1, respectively (p < 0.01 for both); and the decrement in forearm blood flow in nonsmokers was significantly greater than that recorded in smoking subjects (p < 0.05). In this study, long-term cigarette smokers exhibited an impairment in basal, but not stimulated, nitric oxide-mediated vasodilation.
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PMID:Effects of long-term cigarette smoking on endothelium-dependent responses in humans. 883 2

The endothelium lines all vessels of the body and is the most important structure for communication between the flowing blood and the vessel wall. Healthy endothelium has antiadhesive and antithrombotic properties and is crucial for maintaining blood flow. It serves as a permeability barrier and prevents noxious agents from entering the vessel wall. Endothelial cells have secretory functions and secrete vasorelaxant substances. Therefore, functioning endothelium sustains the homoeostasis of the vessel wall. Endothelial functions are impaired by risk factors for cardiovascular disease such as hypertension, hyperlipidemia and hyperglycemia. Hypertension leads to decreased generation of nitric oxide in endothelial cells, thereby diminishing their vasorelaxant properties. Hypertension also contributes to an increase in endothelial cell permeability leading to intimal edema. Thirdly, hypertension increases the expression of adhesion molecules and increases the adherence of leukocytes to the vessel wall. Hence, hypertension directly contributes to the pathological alterations of the endothelium and it seems that these effects initiate and accelerate the pathogenesis of chronic vascular disease.
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PMID:Hypertension, the endothelium and the pathogenesis of chronic vascular disease. 888 53

1. Ligustrazine (tetramethylpyrazine, TMP) is a vasodilator that has been reported to have pulmonary selective properties in vivo, but not in vitro. Although TMP is generally described as being endothelium-independent, we provide evidence here that TMP may have an endothelium-dependent and nitric oxide (NO)-mediated mechanism in pulmonary arteries that could predominate at concentrations used therapeutically in China. 2. The study was performed on isolated pulmonary (1-2 mm i.d.), intrapulmonary (200-850 microns) and mesenteric (200-400 microns) arteries of the rat using a Mulvaney-Halpen small vessel myograph, following preconstriction with phenylephrine (PE, 10 microM), prostaglandin F2 alpha (PGF2 alpha, 100 microM), or 75 mM K+ (KPSS, equimolar substitution for Na+). Values are shown as mean +/- s.e.mean, or for EC50S as mean [+/-95% confidence limits]. 3. TMP caused a concentration-dependent relaxation against all three agonists in both large (1.56 +/- 0.04 mm) and small (399 +/- 20 microM) pulmonary arteries; it was more potent in small compared to large arteries constricted with PE or PGF2 alpha (P < 0.05), but not those constricted with KPSS. The NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA, 100 microM) caused a significant shift to the right of these relationships, such that the EC50 for TMP in large pulmonary arteries constricted with PE increased from 522 [+130, -104] microM (n = 12) to 1828 [+395, -325] microM (n = 6, P < 0.01). Both removal of the endothelium and methylene blue (10 microM) had similar effects. 4. L-Arginine substantially reduced the EC50 for TMP in pulmonary arteries; in the presence of 400 microM L-arginine the EC50 for TMP in large arteries constricted with PE was 14.7 [+21.0, -8.6] microM, (n = 6, P < 0.001), and with 10 microM L-arginine 96.7 [+45.1, -30.7] microM, (n = 6, P < 0.001). Similar effects were seen in small arteries. L-Arginine had no effect in the absence of an endothelium. D-Arginine was ineffective, and inhibition of L-arginine uptake with L-lysine blocked the action of L-arginine. L-Arginine (400 microM) had no significant effect on TMP-induced relaxation in mesenteric arteries (n = 5). 5. L-Arginine itself caused a concentration-dependent relaxation in intrapulmonary arteries (639 +/- 34 microM) constricted with PE, reaching a maximum relaxation around 100-400 microM (42.4 +/- 3.0%, n = 16), but this was independent of the endothelium. TMP (10 and 100 microM) significantly enhanced the relaxation to L-arginine, with a maximum relaxation in the presence of 100 microM TMP of 81.7 +/- 6.2% (n = 5, P < 0.01), but the effect of TMP was entirely dependent on the endothelium. A similar effect was observed in PGF2 alpha-constricted pulmonary arteries. 6. These results show that TMP stimulates NO production at low concentrations in pulmonary arteries, via an apparently novel endothelium-resident mechanism that is dependent on exogenous L-arginine. Normal plasma L-arginine levels of around 150 microM would allow this mechanism to be maximally activated. As mesenteric arteries do not seem to express the mechanism to any significant extent, at low concentrations TMP would be effectively selective to the pulmonary vasculature, and may thus have potential as a therapeutic agent in pulmonary vascular disease.
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PMID:Ligustrazine-induced endothelium-dependent relaxation in pulmonary arteries via an NO-mediated and exogenous L-arginine-dependent mechanism. 892 59

Reducing sugars such as glucose react non-enzymatically with the amino groups of proteins and lipids to initiate a chemical modification pathway known as advanced glycosylation. Recent progress in our understanding of this process has affirmed the hypothesis that advanced glycosylation endproducts (AGEs) play an important role in the evolution of both diabetic and non-diabetic vascular disease. Utilizing newly developed AGE-specific ELISA techniques, AGEs have been identified to be present on a variety of vascular wall, lipoprotein, and lipid constituents. Vascular wall AGEs contribute to vascular pathology by acting to increase vascular permeability, enhance subintimal protein and lipoprotein deposition, and inactivate the endothelium-derived relaxing factor, nitric oxide. Lipid-linked AGEs also have been shown to initiate oxidative modification, thus promoting the formation of oxidized low-density lipoprotein. AGE-specific ELISA analysis has demonstrated a significantly increased level of AGE-modified LDL in the plasma of diabetic patients when compared to normal controls. Furthermore, LDL which has been modified by advanced glycosylation exhibits markedly impaired clearance kinetics in vivo. Thus, AGE-modification impairs LDL-receptor-mediated clearance mechanisms and contributes to elevated LDL levels in patients with diabetes. This concept has been substantiated recently by the clinical observation that administration of the advanced glycosylation inhibitor aminoguanidine to diabetic patients significantly decreases circulating LDL levels.
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PMID:What is the effect of hyperglycemia on atherogenesis and can it be reversed by aminoguanidine? 896 86

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.
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PMID:[Action of natural estrogens on the vessel wall: molecular mechanisms and clinical implications]. 896 7

Oxidized low density lipoprotein (LDL) may be of central importance in triggering atherosclerosis. One potential pathway involves the production of nitric oxide (NO) by vascular wall endothelial cells and macrophages. NO reacts with superoxide to form peroxynitrite (ONOO-), a potent agent of LDL oxidation in vitro. ONOO- nitrates the aromatic ring of free tyrosine to produce 3-nitrotyrosine, a stable product. To explore the role of reactive nitrogen species such as ONOO- in the pathogenesis of vascular disease, we developed a highly sensitive and specific method involving gas chromatography and mass spectrometry to quantify 3-nitrotyrosine levels in proteins. In vitro studies demonstrated that 3-nitrotyrosine was a highly specific marker for LDL oxidized by ONOO-. LDL isolated from the plasma of healthy subjects had very low levels of 3-nitrotyrosine (9 +/- 7 micromol/mol of tyrosine). In striking contrast, LDL isolated from aortic atherosclerotic intima had 90-fold higher levels (840 +/- 140 micromol/mol of tyrosine). These observations strongly support the hypothesis that reactive nitrogen species such as ONOO- form in the human artery wall and provide direct evidence for a specific reaction pathway that promotes LDL oxidation in vivo. The detection of 3-nitrotyrosine in LDL isolated from vascular lesions raises the possibility that NO, by virtue of its ability to form reactive nitrogen intermediates, may promote atherogenesis, counteracting the well-established anti-atherogenic effects of NO.
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PMID:Reactive nitrogen intermediates promote low density lipoprotein oxidation in human atherosclerotic intima. 899 8

Most patients with diabetes die from macrovascular complications. Little is known about the pathogenesis of diabetic vascular disease, but recent advances in molecular genetics and oxidation chemistry provide clues to the mystery of diabetes and atherosclerosis. Genetic variants of well-known proteins such as lipoprotein lipase and apolipoprotein E are common. These proteins are suitable candidates for mediating diabetic vascular risk because their variants can produce hypertriglyceridemia, a risk factor for atherosclerosis in diabetes. However, mutations could have different effects on lipoprotein flux across arteries depending on whether expression is dominant in the vascular space or the vascular wall. Lipoproteins retained in the arterial wall are subject to oxidative modification, which could be dependent on glycoxidation, the enzyme myeloperoxidase, or reactive nitrogen species derived from nitric oxide. Accelerated vascular disease in diabetes is likely the result of complex interactions between metabolic derangements such as hyperglycemia, mutations in genes controlling lipid metabolism, and antioxidant defense mechanisms.
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PMID:The mystery of diabetes and atherosclerosis: time for a new plot. 903 85

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.
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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.
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PMID:[Vascular protection with estrogen. In-vitro and in-vivo effects--mechanisms and clinical implication]. 906 30


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