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)

Angiotensin II (Ang II) importantly contributes to the pathobiology of atherosclerosis. Since endothelial injury is a key event early in the pathogenesis of atherosclerosis, we tested the hypothesis that Ang II may injure endothelial cells by activation of cellular suicide pathways leading to apoptosis. Human umbilical venous endothelial cells (HUVECs) were incubated with increasing doses of Ang II for 18 hours. Apoptosis of HUVECs was measured by ELISA specific for histone-associated DNA fragments and confirmed by DNA laddering and nuclear staining. Ang II dose-dependently induced apoptosis of HUVECs. Simultaneous blockade of both the AT1 and AT2 receptor prevented Ang II-induced apoptosis, whereas each individual receptor blocker alone was not effective. Selective agonistic stimulation of the AT2 receptor also dose-dependently induced apoptosis. Ang II-mediated as well as selective AT2 receptor stimulation-mediated apoptosis was associated with the activation of caspase-3, a central downstream effector of the caspase cascade executing the cell death program. Specific inhibition of caspase-3 activity abrogated Ang II-induced apoptosis. In addition, the NO donors sodium nitroprusside and S-nitrosopenicillamine completely inhibited Ang II-induced apoptosis and eliminated caspase-3 activity. Thus, Ang II induces apoptosis of HUVECs via activation of the caspase cascade, the central downstream effector arm executing the cell death program. NO completely abrogated Ang II-induced apoptosis by interfering with the activation of the caspase cascade.
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PMID:Angiotensin II induces apoptosis of human endothelial cells. Protective effect of nitric oxide. 940 Mar 77

Insulin resistance (IR) and secondary hyperinsulinaemia are major risk factors of atherosclerosis and probably also of related glomerulosclerosis. Angiotensin converting enzyme inhibitors (ACEI), while improving IR in essential hypertension, do not improve it in patients with chronic renal disease. Thus, the combination of ACEI and low protein diet was evaluated. Thirty-eight patients with various kidney diseases and mild to moderate impairment of kidney function were included in the study. Thirteen of them suffered from IR. Their dietary protein intake was decreased from > or = 1.0 g/kg/d to 0.6-0.7 g/kg/d. Moreover, they were treated by ACEI enalapril at dosages of 2-10 mg/d depending on the absence/presence and severity of hypertension. The patients were followed for 8 months. No clinically relevant kidney disease progression (KDP) was found. IR patients improved remarkably. IR was examined by the oral glucose tolerance test and glucose, insulin and C-peptide determinations. Their increased plasma triglyceride, VLDL concentrations and proteinuria decreased, HDL concentration increased. Acid-base balance and anaemia did not change. It is concluded that protein restriction in combination with ACEI treatment improve IR and the associated dyslipoproteinaemia and proteinuria.
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PMID:Dietary protein restriction in combination with angiotensin converting enzyme inhibitor improves insulin resistance in patients with chronic renal disease. 940 10

The ability of the vasculature to modify its geometry in accordance with conditions of its microenvironment--the process of vascular remodeling--is an important pathobiologic process common to vascular disorders such as atherosclerosis, restenosis after angioplasty, and hypertension. Vascular remodeling characterizes the natural history of atherosclerosis, contributes to increased vascular resistance, and may contribute to the clinical complications of hypertension. A growing body of evidence indicates that locally generated vasoactive substances such as angiotensin II and nitric oxide are important determinants of the natural history of vascular disease. In particular, angiotensin II may promote vascular lesion formation by increasing vascular cell population via increased cell growth and decreased programmed cell death, and it may also alter extracellular matrix composition. Thus, angiotensin II is a pleiotropic local mediator capable of modulating cell growth, programmed cell death, migration of vascular smooth muscle cells, and extracellular matrix modulation, all of which are biologic mechanisms of vascular remodeling and intimal formation. This is proposed to occur via a local tissue angiotensin system. Angiotensin II may also promote chronic hypertension by modulating the vascular redox state and promoting the catabolism of the endothelium-derived nitric oxide, an endogenous inhibitory vasodilator. Because angiotensin-converting enzyme (ACE) is strategically positioned to influence the activity of at least three local vasoactive systems--angiotensin II, nitric oxide, and bradykinin--blocking ACE with ACE inhibition may have profound effects on ventricular and vascular structure and function, and have particular efficacy in preventing the morbidity and mortality of vascular diseases such as hypertension and atherosclerosis.
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PMID:Vasculoprotective and cardioprotective mechanisms of angiotensin-converting enzyme inhibition: the homeostatic balance between angiotensin II and nitric oxide. 942 48

The Authors report, in this article, about pathophysiology mechanism that is to the base of the vascular injury mediate from the Angiotensin II able of modulate the primer, the acceleration and the progression of the atherosclerosis. Afterward is considered the importance of the administration of the inhibiting of the receptors AT-1 (Losartan) in the control of the hypertension and of the atherosclerosis.
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PMID:[Physiopathology of angiotensin II and vascular lesion]. 949 56

Two problems in the treatment of hypertension continue to be largely unsolved. The first, and more simple, is our inability to adequately control blood pressure in the majority of hypertensive patients. This not only reflects the difficulty of retaining patients in effective treatment programs, but also of convincing physicians to strive for optimal blood pressure levels. There is a continuing need for new antihypertensive drugs and combinations to help accomplish these goals. The second major problem is that the major clinical endpoints, including coronary events and renal failure, have not been adequately reduced by traditional therapies. Standard regimens, particularly those including diuretics, have protected against strokes and heart failure. Our improved understanding of vascular biology in hypertension has directed interest to the mechanisms in hypertensive patients that might accelerate atherosclerosis and vascular events in these individuals. This involves addressing the concomitant metabolic risk factors that comprise the "Hypertension Syndrome," and, perhaps of equal importance, finding therapies that directly inhibit unwanted types of growth and proliferative activities within the walls of critical arteries. Many substances within the endothelium and the vascular wall may participate as initiators or mediators of pathology, but most information thus far has focused on the renin-angiotensin system. Angiotensin converting enzyme inhibitors (and potentially angiotensin receptor blockers) have provided coronary and renal protection in various cardiovascular conditions, though not yet in formal hypertension trials. Calcium channel blockers have also shown promise, including recent stroke and cardiovascular benefits in patients with isolated systolic hypertension, but, again, definitive coronary data in hypertension are awaited. Unless concomitant conditions mandate the selection of a particular antihypertensive drug class, physicians currently have a dilemma: should they choose drugs from older classes that have not provided full protection? Or, should they prescribe newer agents with exciting potential but with, as yet, unproved endpoint benefits in hypertension? Until currently ongoing prospective trials of antihypertensive therapy are completed, physicians must be guided by their own interpretations of the available data.
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PMID:Translating data on antihypertensive drugs into clinical practice. 965 68

Angiotensin II (AII) receptor type 1 (AT1), a G-protein-coupled receptor, is involved in the development of cardiovascular diseases such as hypertensin, cardiac hypertrophy, and atherosclerosis. Recent reports indicate that tyrosine phosphorylation of multiple intracellular molecules is responsible for most of these AII actions mediated by AT1, similar to receptor tyrosine kinase signaling pathways. AII activates MAPK by tyrosine phosphorylating the EGF receptor by the mechanism called transactivation with subsequent Ras activation in vascular smooth muscle and cardiac fibroblast cells. In contrast, AT1 leads to MAPK activation through PKC in cardiac myocytes. In addition to these signals, JAK/STAT pathways, which mediate cytokine actions, are also important for several AII functions through AT1.
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PMID:[Intracellular signaling pathways of angiotensin II receptor type 1 involved in the development of cardiovascular diseases]. 970 74

Angiotensin-converting enzyme (ACE) inhibitors have shown unexpected benefits in the prevention of ischemic events in patients with hypertension and congestive heart failure. In addition to these clinical observations, there is a growing body of knowledge about the molecular and cellular effects of ACE inhibitors. For example, ACE inhibition prevents stimulation of smooth muscle cell angiotensin II receptors, thereby blocking both contractile and proliferative actions. Angiotensin II blockade also diminishes the production of superoxide anion, which inactivates ambient nitric oxide. ACE inhibition of kininase II inhibits the breakdown of bradykinin, a direct stimulant of nitric oxide release from the intact endothelial cell. Thus, at the cellular level within the vasculature, ACE inhibition shifts the balance of ongoing mechanisms in favor of those promoting vasodilatory, antiaggregatory, antithrombotic, and antiproliferative effects. These effects underlie the potential benefits of ACE inhibition in the therapy of ischemia and atherosclerosis. Some data is available in humans to show that these effects can be sustained for months, thereby maintaining improved endothelial function and, presumably, allowing the initiation of steps that might alter the progression of atherosclerosis. Definitive information is not yet available in humans to show that ACE inhibition clearly alters the progression of atherosclerosis or diminishes coronary events in uncomplicated coronary disease. This promising area of investigation is, however, the subject of multiple clinical trials, which should provide clarification of this important question in coming years.
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PMID:Role of angiotensin-converting enzyme inhibition in reversal of endothelial dysfunction in coronary artery disease. 970 67

Angiotensin II (Ang II) promotes vascular smooth muscle growth and may be involved in the initiation and progression of atherosclerosis. To examine whether Ang II receptor expression in vascular tissues is altered in atherosclerosis, male New Zealand White rabbits were fed a high-cholesterol diet (1% cholesterol + 4% coconut oil mixed with regular chow; hypercholesterolemic group, n=12) or regular chow (control group, n=8) for 10 weeks. At the end of this period, the serum cholesterol level in the rabbits fed the high-cholesterol diet was higher than that in the control group (3616 +/- 144 versus 30 +/- 1 mg/dL, P<0.001). There was no atherosclerosis in the aortas of the control group, whereas 51 +/- 6% of the aorta was covered with atherosclerosis in the hypercholesterolemic group. Total Ang II receptor expression in the atherosclerotic aortic tissues was increased 5-fold in the hypercholesterolemic rabbits (292 +/- 28 versus 51 +/- 32 fmol/mg tissue, mean +/- SE, P<0.001), and the increased Ang II receptor expression was entirely due to enhanced Ang II type 1 (AT1) receptor expression (289 +/- 38 versus 38 +/- 18 fmol/mg, P<0.001), as Ang II type 2 receptor expression was unaltered (7 +/- 5 versus 3 +/- 2 fmol/mg, P=NS). AT1 receptors were localized primarily in the media and to some extent in the intima of the atherosclerotic aorta, as determined by immunohistochemistry with specific monoclonal and polyclonal AT1 receptor antibodies. Increased synthesis of AT1 receptor mRNA in atherosclerotic tissues was confirmed by reverse transcription-polymerase chain reaction. To evaluate the functional significance of increased AT1 receptor expression, the constrictor response of aortic rings to Ang II was examined and found to be markedly enhanced in atherosclerotic aortic rings (P<0.01 versus control aortic rings). The endothelium-dependent relaxation of aortic rings from hypercholesterolemic rabbits was markedly attenuated (P<0.001). This study shows that hypercholesterolemia in rabbits results in atherosclerosis, loss of endothelium-dependent relaxation, and increased Ang II receptor (entirely AT1 receptor) expression in aortic tissues, which may result in altered vasoreactivity.
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PMID:Increased angiotensin II type 1 receptor expression in hypercholesterolemic atherosclerosis in rabbits. 974 32

Cell-surface expression of endothelial P-selectin increases adhesion and migration of leukocytes and thus may participate in the pathogenesis of reperfusion injury and atherosclerosis. Angiotensin II (Ang II) is also thought to be involved in such disease states. Nitric oxide (NO) downregulates P-selectin expression, and bradykinin (BK) is known to stimulate NO release from endothelial cells. The objective of this study was to determine the effects of 10-min stimulation of cultured human umbilical endothelial cells (HUVECs) with Ang II, BK, or both on P-selectin expression. Ang II (10(-9)-10(-5) M) stimulated P-selectin expression in a concentration-dependent manner, exhibiting a significant effect at 10(-7) M and reaching a plateau at 5 x 10(-5) M. Pretreatment of HUVECs with the AT1 antagonist losartan and the AT1/AT2 antagonist saralasin but not the AT2 antagonist PD123319 (all at 10(-5) M) markedly attenuated the effect of 10(-7) M Ang II. The effects of Ang II on P-selectin expression were not affected by the presence of the NO synthase inhibitor nitro-L-arginine (L-NA, 5 x 10(-4) M) but were abolished by pretreatment with superoxide dismutase (SOD). BK (10(-6) M) abolished the effects of 10(-7) M Ang II on P-selectin expression but did not affect P-selectin expression induced by desmopressin (0.01-10 microM). L-NA obliterated the blunting effect of BK on the Ang II-induced P-selectin membrane expression. BK alone slightly stimulated P-selectin expression, but in the presence of L-NA, BK markedly enhanced P-selectin expression. The effects of BK in the presence of NA were not altered by SOD, indicating that at difference with Ang II, it acts by a mechanism other than superoxide generation. Thus, Ang II acting on AT1 receptors stimulates superoxide generation, which, in turn, induces expression of P-selectin on the endothelial cell surface. BK inhibits the effects of Ang II, likely acting via NO. We conclude that the balance between Ang II, BK, and NO can regulate P-selectin expression on the endothelial cell membrane, an important component of the cascade leading to leukocyte adhesion to the vascular endothelium.
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PMID:Angiotensin II and bradykinin regulate the expression of P-selectin on the surface of endothelial cells in culture. 975 92

Angiotensin, a vasoconstrictive peptide, is now known to be an agent of vascular oxidative stress, vascular growth and inflammation, and may directly influence the pathophysiology of coronary artery disease (CAD). The presence of angiotensin-converting enzyme (ACE) and angiotensin II have been demonstrated in vascular tissue, and these local substances are causally involved in the development of vascular lesions. Recent clinical trials in post-myocardial infarction reported that ACE inhibitor therapy reduces recurrent myocardial infarction and prevents cardiac enlargement. Long-term prospective trials are currently being conducted to examine the effects of ACE inhibitor therapy on coronary ischaemic events and coronary atherosclerosis. This paper reviews angiotensin's role in the pathophysiology of CAD and the mechanisms of ACE inhibitor effects.
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PMID:Mechanism of protective effects of ACE inhibition on coronary artery disease. 979 34


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