Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The seronin or 5-hydroxytryptamine (5-HT) is a biogenic amine involved in diverse physiologic and physiopathological processes in the cardiovascular system. 5-HT may lower the arterial blood pressure by an action on central 5-HT1A receptors, or may increase it by stimulation of 5-HT2 receptors located in vascular smooth muscle. It has been postulated that hypofunction of 5-HT1A receptors, or the exaggerated stimulation of 5-HT2 receptor may be associated with arterial hypertension and that agonists of the first type (indorenate or 8-OH-DPAT) or antagonists of the second type (ketanserin or pelanserin) allow the control of arterial hypertension. On the other land, ketanserin and pelanserin attenuated the hemodynamic manifestations in an experimental model of thromboembolism, suggesting that 5-HT is involved in such phenomenon. Finally, 5-HT could be related with the presence of angor pectoris during hypertension or atherosclerosis, diseases that are associated with a lesional of the vascular endothelium, a condition that favors the 5-HT induced vasoconstriction in coronary arteries.
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PMID:[Serotoninergic receptors and cardiovascular diseases]. 765 75

Nitric oxide (NO), which accounts for the biological properties of endothelium-derived relaxing factor, is generated by NO synthase (NOS). The vascular endothelium contains two types of NOS: one is constitutively expressed (cNOS), and the other is inducible. Endothelium-mediated vasorelaxation is impaired in atherosclerotic vessels. To determine whether tumor necrosis factor (TNF)-alpha, which is commonly found in atherosclerotic lesions, has an effect on NOS message, we measured cNOS mRNA levels in TNF-treated human umbilical vein endothelial cells (HUVECs) by RNA blot analysis with a cNOS cDNA probe. TNF-alpha markedly reduced cNOS mRNA levels in HUVECs in a dose- and time-dependent manner. In response to 3 ng/mL TNF-alpha, cNOS mRNA levels began to decrease at 4 hours and diminished to only 5% of control levels at 24 hours. As little as 0.1 ng/mL TNF-alpha reduced cNOS mRNA levels by 50%. This reduction in cNOS message in response to TNF-alpha depended on protein synthesis as it was blocked by cycloheximide. In nuclear runoff experiments, TNF-alpha did not change the rate of cNOS gene transcription. cNOS mRNA is very stable under basal conditions, with a half-life of 48 hours; however, treatment with TNF-alpha shortened this half-life to 3 hours. TNF-alpha thus appears to decrease cNOS mRNA levels by increasing the rate of mRNA degradation. TNF-induced reductions in cNOS mRNA levels may have an important effect on impaired endothelium-mediated vasorelaxation in atherosclerosis.
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PMID:Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. 768 52

Advances in the studies on the structure and role of adhesive particles make possible putting forward of the hypothesis that they may also play a significant role in the immunopathogenesis of atherosclerosis. It was demonstrated that in the earliest phase of atherosclerosis development, increased adhesion occurred of monocytes to the vascular endothelium, while autopsy examinations showed the presence of monocytes and T-cells within atherosclerotic lesions. The present studies concentrate on the role of individual adhesive particles as determinants of the above phenomena.
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PMID:[The role of adhesion molecules in the immunopathogenesis of atherosclerosis]. 770 51

1. Endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation are key events in the pathogenesis of atherosclerosis. Vascular permeability factor (VPF), an endothelial-cell-specific multifunctional cytokine, was recently described, and has the potential to contribute to the development of endothelial dysfunction. The present study determines whether cultured human VSMCs express mRNA for VPF and whether VPF mRNA expression is influenced by human VSMC proliferation. 2. A 204 bp cDNA fragment, specific for all known variants of VPF mRNA, was cloned and used to demonstrate that human VSMCs express abundant quantities of VPF mRNA, whereas human endothelial cells do not. VPF mRNA levels were markedly diminished in non-proliferating human VSMCs. In contrast, when human VSMCs were stimulated to proliferate by exposure to serum, there was a rapid 6.6-fold increase (P < 0.01 versus time 0 h) in VPF mRNA expression, which was maximal at 3 h and persisted beyond 24 h. The magnitude of the VPF mRNA response in human VSMCs was dependent on the serum concentration. 3. Platelet-derived growth factor also increased VPF mRNA expression by human VSMCs, thus confirming that recognized growth factors for VSMCs also potently influence the VPF gene. 4. In conclusion, VPF mRNA is expressed by human VSMCs, the magnitude of VPF expression being temporally related to the proliferation of human VSMCs and the potency of the growth-promoting stimulus. We propose that VPF produced by proliferating human VSMCs could act as a paracrine hormone to powerfully influence the permeability and growth of the overlying vascular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum and platelet-derived growth factor-induced expression of vascular permeability factor mRNA by human vascular smooth muscle cells in vitro. 772 Mar 37

Angiotensin II (Ang II) has been implicated in the pathogenesis of the vascular injury associated with hypertension and diabetes mellitus. Increased vascular permeability is an important early manifestation of endothelial dysfunction and the pathogenesis of atherosclerosis. How Ang II contributes to endothelial dysfunction and promotes an increase in vascular permeability is unknown but is classically attributed to its pressor actions. We demonstrate that human vascular smooth muscle cells express abundant mRNA for vascular permeability/endothelial growth factor. Vascular permeability factor is a 34- to 42-kD glycoprotein that markedly increases vascular endothelial permeability and is a potent endothelial mitogen. Ang II potently induced a concentration-dependent (maximal, 10(-7) mol/L) and time-dependent increase in vascular permeability factor mRNA expression by human vascular smooth muscle cells that was maximal after 3 hours and diminished by 24 hours. Ang II-induced vascular permeability factor mRNA expression by human vascular smooth muscle cells was inhibited by the specific Ang II receptor antagonist losartan (DuP 753), confirming that this is an Ang II receptor subtype 1-mediated event. These results describe a new action of Ang II on human vascular smooth muscle, notably the induction of vascular permeability factor mRNA expression. The wide spectrum and potent activity of vascular permeability factor suggest a novel mechanism whereby Ang II could locally and directly influence the permeability, growth, and function of the vascular endothelium independent of changes in hemodynamics.
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PMID:Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. 773 26

Various forms of cellular injury, whether induced by immune effector cells, aberrant metabolic processes, chemotherapeutic drugs or temperature shifts, result in common morphological changes consisting of the formation and shedding of membrane vesicles from the injured cell surfaces, i.e., apoptosis. This dynamic cell surface membrane behavior appears to be dependent on the disruption of cytoplasmic microtubules. Concomitant with the altered cell surface morphology, certain physiological and biochemical events have been found to be associated with cell injury. These include changes in membrane permeability, elevated oxygen consumption rates and nuclear DNA fragmentation. However, it remains to be experimentally established which of these biological changes defines a state of irreparable cell injury and/or programmed cell death (PCD). Selective cell injury and death is the goal of many therapeutic modalities aimed at the destruction of malignant cells. On the other hand, prevention of cell injury is desirable in autoimmune diseases such as systemic lupus erythematosus, thyroiditis, insulin dependent diabetes and many others. Injury to the vascular endothelium may play a role not only in thrombosis, atherosclerosis and hypertension, but may also provide the avenues for the metastasis of malignant cells. The objective of the present review is to compare and evaluate the cell injury process induced by effector lymphocytes with that caused by low temperature. The latter mimics most, if not all, the currently known criteria of immune effector cell mediated PCD of target tumor cells.
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PMID:Cell injury and apoptosis. 774 62

Nitric oxide derived from the vascular endothelium and other cells of the cardiovascular system has important roles in physiological regulation of blood flow and may have pathophysiological functions in cardiovascular disease. Nitric oxide can be synthesised from L-arginine by any of three isoforms of nitric oxide synthase (NOS), and its interaction with prostacyclin, its proposed mechanisms of action and cytotoxicity are briefly reviewed in the context of cardiovascular function. Although nitric oxide can hyperpolarize vascular smooth muscle, activation of the endothelium can induce hyperpolarization and vasodilatation by other means. Nitric oxide has important roles in the physiological regulation of local blood flow and blood pressure, especially during exercise and in response to shear stresses and other local factors in arterioles. Nitric oxide is also involved in neurogenic control of the microcirculation through autonomic efferent nerves and it contributes to vasodilatation and inflammation associated with activation of sensory nerves. In pathological circumstances, excess nitric oxide produced by inducible NOS compromises circulatory function in septic shock, during transplant rejection, and during myocardial ischaemia and reperfusion injury. Immunosuppressant drugs like cyclosporin A inhibit the expression of NOS through complex intracellular intermediates. Disturbances in the activity of constitutive and inducible NOS in the artery wall accompany the development of atherosclerosis, vasospasm and thrombosis, and may contribute to some forms of hypertension and diabetic vascular disease. Reversing the nitric oxide defect with therapeutic agents including angiotensin-converting enzyme inhibitors offers promise in protecting against some manifestations of vascular disease.
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PMID:Nitric oxide in cardiovascular disorders. 777 76

Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL-1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.
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PMID:Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. 778 64

Recent experimental findings suggest that we should now consider some diseases as "endotheliopathies" and some others as "ROS-pathies". The presented review summarizes our knowledge on the role of endothelium and reactive oxygen species (ROS) in physiological processes and diseases. The vascular endothelium provides vital and responsive infrastructure of vessels for the circulation of blood and homeostasis of all organs. Due to its exposure to mechanical, chemical and biological factors, including ROS and the nature of its responses to these insults, it is involved in a wide variety of disease processes. Oxidative stress occurs also in many human diseases. Our understanding of the role played by the endothelium and ROS in disease pathology are still insufficient. To determine if endothelial and ROS-induced changes in hypertension, atherosclerosis, ischemia/reperfusion etc. are the primary cause of specific diseases or merely secondary effects remains to be clarified in several areas from inflammatory processes to cardiovascular diseases. Protection of the endothelium and antioxidant therapy represents a potential successful therapeutic approach in different diseases. In the near future the endothelial and free radical research will surely clarify many of our still unanswered questions.
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PMID:[Endothelium and reactive forms of oxygen]. 781 26

Oxidative damage to the vascular endothelium may be an important event in the promotion of atherosclerosis. Several lines of evidence suggest that lipid hydroperoxides may be responsible for the induction of such damage. Hydroperoxides cause loss of endothelial cell integrity, increase the permeability of the endothelium to macromolecules, and compromise its ability to control vascular tone via the secretion of vasoactive molecules in response to receptor stimulation. The molecular mechanisms responsible for these effects are, however, poorly understood. In this paper, we describe an e.s.r. spin-trapping investigation into the metabolism of the model hydroperoxide compound tert-butylhydroperoxide to reactive free radicals in intact human endothelial cells. The hydroperoxide is shown to undergo a single electron reduction to form free radicals. Experiments with metabolic poisons indicate that the mitochondrial electron-transport chain is the source of electrons for this reduction. The metal-ion-chelating agent desferrioxamine was found to prevent cell killing by tert-butylhydroperoxide, but did not affect free radical formation, suggesting that free metal ions may serve to promote free-radical chain reactions involved in cell killing following the initial conversion of the hydroperoxide to free radicals by mitochondria. These processes may well be responsible for many of the reported effects of hydroperoxides on endothelial cell integrity and function.
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PMID:Mitochondrial metabolism of a hydroperoxide to free radicals in human endothelial cells: an electron spin resonance spin-trapping investigation. 781 71


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