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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The primary mechanism of activation of baroreceptors is mechanical deformation during vascular stretch. In addition, baroreceptor activity is modulated by ionic mechanisms and by neurohumoral and paracrine factors that act directly on the nerve endings. 2. Ionic mechanisms play a major role in causing baroreceptor activity to decline during a sustained increase in arterial pressure (adaptation) and in the suppression of activity that occurs after pressure returns to basal levels (post-excitatory depression). Activation of a 4-aminopyridine-sensitive K+ channel contributes to adaptation, whereas activation of an electrogenic sodium pump is responsible for post-excitatory depression. 3. Factors released from vascular endothelium exert powerful effects on baroreceptor sensitivity. Prostacyclin increases baroreceptor sensitivity and contributes to baroreceptor activation during vascular stretch. Nitric oxide, endothelin and oxygen-derived free radicals suppress baroreceptor activity particularly at high levels of arterial pressure. The sympathetic neurotransmitter norepinephrine modulates baroreceptor activity: a) indirectly through its vasoconstrictor action, b) directly by binding to alpha-adrenergic receptors on the nerve endings, and c)through release of a cyclooxygenase metabolite, possibly prostacyclin, from endothelium. 4. Endothelial dysfunction contributes to baroreceptor impairment in atherosclerosis and in chronic hypertension. Loss of the excitatory influence of prostacyclin and increased formation of free radicals and possibly endothelin contribute to the baroreceptor dysfunction. Platelets aggregating at sites of endothelial damage in the carotid sinus release a stable diffusible factor that impairs baroreceptor sensitivity. 5. Therapeutic interventions may alter baroreceptor sensitivity through paracrine mechanisms. Treatment of hypertension or atherosclerosis may improve baroreceptor sensitivity by restoring endothelial function. Antiplatelet agents may enhance baroreceptor sensitivity. Antidepressant agents may decrease baroreceptor sensitivity by inhibiting prostacyclin and/or stimulating nitric oxide formation, which may contribute to dysregulation of the circulation in patients treated for depression.
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PMID:Modulation of baroreceptor activity by ionic and paracrine mechanisms: an overview. 752 78

Key discoveries in the past decade have revealed that the vascular endothelium is an important regulatory organ that is involved in maintaining cardiovascular homeostasis in health and contributes significantly to the pathomechanism of several cardiovascular diseases. Occupying a strategically important location between circulating blood and tissues and having the ability to respond to changes in its physical, chemical, and humoral environment by the production of a host of biologically active substances, the normal endothelium modulates the tone of underlying vascular smooth muscle, maintains a nonadhesive luminal surface, and mediates hemostasis, cellular proliferation, and inflammatory and immune mechanisms in the vascular wall. Modulation of smooth-muscle tone is mediated by the synthesis release of endothelium-derived relaxing [PGI2, EDRF(NO), and EDHF] and contracting factors (arachidonic acid metabolites, endothelin-1, and angiotensin II). Anticoagulant, fibrinolytic, and antithrombotic properties contribute to the maintenance of the fluidity of blood. Injury or activation (by cytokines) of endothelial cells disrupts these normal regulatory mechanisms and results in morphologic and functional alterations (phenotypic changes) commonly defined as endothelial dysfunction. Clinically, the "syndrome" of endothelial cell dysfunction can be described as generalized or localized vasospasm, thrombosis, atherosclerosis, and restenosis. Although its importance is clearly established, no drugs used today were originally targeted for the treatment of endothelial dysfunction. Recent studies, however, showed that some existing therapies (e.g., angiotensin-converting enzyme inhibitors) may protect the endothelium. Novel diagnostic techniques and innovative therapeutic strategies, based on the already known molecular mechanisms of endothelial dysfunction, are briefly outlined. Further knowledge of the pathobiology of the impaired endothelium will contribute to unraveling some of the remaining mysteries of many cardiovascular diseases and will enable us to design novel therapies to prevent and treat them.
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PMID:The role of endothelium in cardiovascular homeostasis and diseases. 752 67

Vascular endothelium, the single-cell-thick lining of the cardiovascular system, is an important functional component of the blood vessel wall, actively participating in normal vascular physiology as well as the pathogenesis of vascular diseases such as atherosclerosis. The localized modulation of vascular endothelium to a non-adaptive functional state can be termed "endothelial dysfunction." This article provides a brief overview of endothelial dysfunction, especially as it relates to mononuclear leukocyte recruitment during atherosclerotic lesion formation. Potential diagnostic and therapeutic implications are also considered.
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PMID:Vascular endothelium: an integrator of pathophysiologic stimuli in atherosclerosis. 786 77

The effect of hypertension on the arterial vascular wall is characterised primarily by morphological changes to the endothelium and hypertrophy of smooth muscle cells within the arterial media. Endothelial dysfunction is manifest through increased permeability to high molecular weight compounds as well as mitogenic and vasoactive substances. At the same time, denudation of the vascular endothelium promotes platelet aggregation and subsequent release of platelet-derived growth factor (PDGF). In conjunction with endothelium- and monocyte-derived growth factors, this mitogen stimulates subintimal smooth muscle cell proliferation and migration and arterial wall thickening, resulting in a haemodynamically important increase in vascular resistance, particularly at the precapillary level. In addition, focal endothelial dysfunction allows entry of lipids into the vascular wall, thereby promoting formation of a lipid-rich fatty streak, the primary 'early' atherosclerotic lesion. Most of these changes, including endothelial injury, subintimal lipid-binding, cellular proliferation and migration, platelet aggregation and PDGF release are common to both hypertensive and early atherosclerotic processes and involve the participation of calcium ions as 'second messengers'. Thus, antihypertensive treatment with calcium antagonists may not only lead to a protective decrease in wall shear stress through a reduction in blood pressure, but may also inhibit those cellular processes within the vascular wall that are responsible for initiating atherosclerosis. Indeed, experimental as well as human studies have demonstrated a beneficial suppressant effect of calcium antagonists on the early stages of atherosclerosis.
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PMID:Hypertension treatment and prevention of new atherosclerotic plaque formation. 753 1

PHYSIOLOGICAL EFFECTS OF NITRIC OXIDE: The generation of nitric oxide by the vascular endothelium maintains a vasodilator tone that is essential for the regulation of blood flow and pressure. In the brain, nitric oxide acts as a mediator of cell-cell signalling. In the peripheral nervous system nitric oxide is also released from many nerves previously classified as non-adrenergic and non-cholinergic. Thus this simple gaseous molecule performs a wide variety of physiological functions. POTENTIAL FOR THERAPEUTIC MANIPULATIONS: Impaired production of nitric oxide can be countered by the administration of nitric oxide donors (in hypertension, atherosclerosis, gastrointestinal and genitourinary disorders) or by inhalation of nitric oxide gas (in chronic pulmonary hypertension or adult respiratory distress syndrome). The biggest challenge is to develop strategies that target the cytotoxic and damaging actions of nitric oxide without interfering with its essential protective functions.
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PMID:Nitric oxide. 753 93

Nitric oxide (NO), 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. The mechanisms involved in NO-induced vasodilatation and cytotoxicity are briefly reviewed in the context of inflammatory reactions and cardiovascular function. Although NO can hyperpolarize vascular smooth muscle, activation of the endothelium can induce hyperpolarization and vasodilatation by other means. Endogenous inhibitors of NO generated by leucocytes may compromise blood flow distribution after ischaemia and reperfusion injury. Chronic heart failure is associated simultaneously with impairment of endothelium-dependent vasodilatation and with excess production of NO via the inducible NO synthase (iNOS), although it is unclear whether the latter ameliorates or exacerbates ventricular dysfunction. Excess NO production is also one of the earliest signs of transplant rejection, and suppression of iNOS expression by immunosuppressant drugs such as cyclosporin A might be one means by which these drugs protect allografts. Disturbances in the activity of NOS isoforms in the artery wall also accompany the development of atherosclerosis, providing conditions propitious for vasospasm and thrombosis. Reversing the NO defects with therapeutic agents, including angiotensin converting enzyme (ACE) inhibitors, offers promise in protecting against some manifestations of vascular disease.
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PMID:Endogenous nitric oxide in cardiovascular disease and transplantation. 754 30

The vascular endothelium plays a central role in the regulation of vascular function. In particular, the local release of endothelium-derived relaxing factor (EDRF) regulates vascular tone and prevents platelet adhesion to the vascular wall. Impairment of EDRF action develops early in atherosclerosis and, in part, contributes to platelet deposition and vasospasm involved in the clinical expression of coronary artery disease. Recent evidence suggests that an imbalance between vascular oxidative stress and antioxidant protection is involved in the development of this vascular dysfunction. In this report, the relation between oxidative stress, atherosclerosis, and abnormal EDRF action is reviewed with particular attention to the effects of antioxidant supplementation in animal models of atherosclerosis and hypercholesterolemia.
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PMID:Atherosclerosis, oxidative stress, and antioxidant protection in endothelium-derived relaxing factor action. 756 3

Through their specific biological properties, vascular endothelial cells play a major role in maintaining the homeostasis of the cardiovascular system. The vascular endothelium participates actively in coagulation and fibrinolysis, contributes to regulating vascular tone, is involved in inflammation and immunological responses, produces several different stromal components, plays a crucial role in angiogenesis and wound-healing, and interacts with plasma lipoproteins. These physiological functions of endothelial cells are triggered by different endothelium derived mediators and are regulated by numerous environmental factors that can markedly modulate the functional state of these cells by affecting their biosynthetic capabilities, giving them different phenotypes in native, activated and injured states. Excessive endothelial activation leads to changes in endothelial cell gene expression, leading to what is referred to as a dysfunctional state. In this non-adaptative functional state, endothelial cells lose the ability to adjust, within the physiological range, some of their constitutive functions and express newly induced molecules, some of which act as proatherosclerotic factors. Activated endothelial cells thus participate actively in the pathogenesis of atherosclerosis.
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PMID:[Biology of the endothelial cell and atherogenesis]. 757 4

The relationship between antioxidants and endothelial cell injury was examined in 119 patients with (n = 48) or without (n = 71) vascular disease who were attending a hyperlipidaemia clinic. Serum levels of total antioxidant capacity, glutathione peroxidase (a protein antioxidant), von Willebrand factor (vWf, a specific endothelial cell product and marker of injury) and routine lipids were measured in the patients and from 58 healthy controls. Compared to controls, total antioxidant capacity (P < 0.01) and glutathione peroxidase (P < 0.0001) were lower whilst vWf was higher (P < 0.0001) amongst the patients. Comparing patients with and without vascular disease, glutathione peroxidase was lower (P < 0.03) and vWf was higher (P < 0.05) in the presence of vascular disease but there was no difference in levels of serum lipids or total antioxidant capacity. vWf and glutathione peroxidase were inversely correlated (r = -0.26, P < 0.005). We conclude that patients with hypercholesterolaemia have reduced antioxidant capacity and this is most severe in patients with clinically apparent vascular disease. This, linked to the finding of increased vWf in hypercholesterolaemia with highest levels in those patients with vascular disease, suggests that loss of antioxidant capacity may expose the vascular endothelium to excess oxidative damage. These results suggest a link between hypercholesterolaemia, impaired ability to resist free radical attack, and the development of atherosclerosis.
Atherosclerosis 1995 Aug
PMID:Antioxidants, von Willebrand factor and endothelial cell injury in hypercholesterolaemia and vascular disease. 757 74

The development of atherosclerosis is thought to be initiated by a dysfunctional state of the vascular endothelium. The proposal that mechanical forces play a role in the localization of this disease has led researchers to develop in vitro models to assess their effects on cultured endothelial cells. The arterial endothelium is exposed simultaneously to circumferential hoop stretch and wall shear stress, yet previous investigations have focused on the isolated effects of either cyclic stretch or shear stress. The influence of physiological levels of combined shear stress and hoop stretch on the morphology and F-actin organization of bovine aortic endothelial cells was investigated. Cells subjected for 24 hours to shear stresses higher than 2 dyne/cm2 or to hoop stretch greater than 2% elongated significantly compared with unstressed controls and oriented along the direction of flow and perpendicular to the direction of stretch. Exposure to more than 4% stretch significantly enhanced the responses to shear stress. Both shear stress and hoop stretch induced formation of stress fibers that were aligned with the cells' long axes. Simultaneous exposure to both stimuli appeared to enhance stress fiber size and alignment. These results indicate that shear stress and hoop stretch synergistically induce morphological changes in endothelial cells, which suggests that circumferential strain might modulate sensitivity of endothelial cells towards shear stress.
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PMID:Synergistic effects of fluid shear stress and cyclic circumferential stretch on vascular endothelial cell morphology and cytoskeleton. 758 56


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