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

Angiotensin-converting enzyme (ACE) inhibitors appear to possess unique cardioprotective benefits, even when used in patients without high blood pressure or left ventricular dysfunction (the traditional indications for ACE inhibitor therapy). The ACE inhibitors improve endothelial function and regress both left ventricular hypertrophy and arterial mass better than other antihypertensive agents that lower blood pressure equally as well. These agents promote collateral vessel development and improve prognosis in patients who have had a coronary revascularization procedure (i.e., percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery). Insulin resistance, present not only in type 2 diabetes but also commonly in patients with hypertension or coronary artery disease, or both, sensitizes the vasculature to the trophic effects of angiotensin II and aldosterone. This may partly explain the improvement in prognosis noted when patients who have atherosclerosis or diabetes are treated with an ACE inhibitor. Therapy with ACE inhibitors has also been shown, in two large, randomized trials, to reduce the incidence of new-onset type 2 diabetes through largely unknown mechanisms. The ACE inhibitors are safe, well tolerated and affordable medications. The data suggest that most people with atherosclerosis should be considered candidates for ACE inhibitor therapy, unless they are intolerant to the medication, or have systolic blood pressures consistently <100 mm Hg. Patients who show evidence of insulin resistance (with or without overt type 2 diabetes) should also be considered as candidates for prophylactic ACE inhibitor therapy. Although angiotensin receptor blockers should not be considered equivalent to ACE inhibitors for this indication, they may be a reasonable alternative for patients intolerant of ACE inhibitors.
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PMID:Should an angiotensin-converting enzyme inhibitor be standard therapy for patients with atherosclerotic disease? 1115 22

Angiotensin-converting enzyme (ACE) is mainly responsible for converting angiotensin I (AI) to angiotensin II (AII), and ACE inhibitors prevent atherosclerosis in animal models. Neutral endopeptidase 24.11 (NEP) degrades substance P, kinins and atrial natriuretic peptide (ANP), and aortic wall NEP activity was found to be increased in atherosclerosis. In the present study, we have evaluated the effect of candoxatril, a NEP inhibitor, and of omapatrilat, a dual ACE and NEP inhibitor, on the development of fatty streak in apolipoprotein E (apoE)-deficient mice. Groups of ten male apoE-deficient mice were given either placebo, candoxatril 50 mg/kg per day, or omapatrilat 10, or 100 mg/kg per day for 4 months. None of the treatments influenced body weight, serum total or HDL-cholesterol. Compared with the placebo, candoxatril did not protect the mice from fatty streak deposit. In contrast, omapatrilat dose dependently inhibited the constitution of fatty streak in apoE-deficient mice. The precise advantages of the dual ACE and NEP inhibition versus the inhibition of only ACE should now be considered in the prevention of atherosclerosis as well as in the occurrence of its complications.
Atherosclerosis 2001 Apr
PMID:Omapatrilat, a dual angiotensin-converting enzyme and neutral endopeptidase inhibitor, prevents fatty streak deposit in apolipoprotein E-deficient mice. 1125 98

Angiotensin-converting enzyme inhibitors improve endothelial function, inhibit experimental atherogenesis, and decrease ischemic events. The Quinapril Ischemic Event Trial was designed to test the hypothesis that quinapril 20 mg/day would reduce ischemic events (the occurrence of cardiac death, resuscitated cardiac arrest, nonfatal myocardial infarction, coronary artery bypass grafting, coronary angioplasty, or hospitalization for angina pectoris) and the angiographic progression of coronary artery disease in patients without systolic left ventricular dysfunction. A total of 1,750 patients were randomized to quinapril 20 mg/day or placebo and followed a mean of 27 +/- 0.3 months. The 38% incidence of ischemic events was similar for both groups (RR 1.04; 95% confidence interval 0.89 to 1.22; p = 0.6). There was also no significant difference in the incidence of patients having angiographic progression of coronary disease (p = 0.71). The rate of development of new coronary lesions was also similar in both groups (p = 0.35). However, there was a difference in the incidence of angioplasty for new (previously unintervened) vessels (p = 0.018). Quinapril was well tolerated in patients after angioplasty with normal left ventricular function. Quinapril 20 mg did not significantly affect the overall frequency of clinical outcomes or the progression of coronary atherosclerosis. However, the absence of the demonstrable effect of quinapril may be due to several limitations in study design.
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PMID:The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function. 1172 75

Angiotensin-converting enzyme (ACE) and cytokines are considered to play an important role in the pathophysiology of cardiovascular diseases such as atherosclerosis. In the present study, the effects of the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) on ACE in cultured human umbilical vein endothelial cells (HUVECs) was studied. TNF-alpha (0.1-10 ng/ml) and IL-1beta (0.1-10 ng/ml) caused a dose- and time-dependent decrease in the amount of ACE in intact endothelial cell membranes and decreased levels of ACE mRNA. TNF-alpha and IL-1beta activated p44/42 and p38 mitogen-activated protein kinases (MAPKs) in HUVECs; this was inhibited by the specific inhibitors of these kinases, PD98059 and SB202190, respectively. Pretreatment of endothelial cells with the specific p38 MAPK inhibitor SB202190 (5 microM) or hydrocortisone (5 microM) partly reversed the suppression of ACE by TNF-alpha or IL-1beta, whereas the specific p44/42 MAPK inhibitor PD98059 (40 microM) was without effect. Vascular endothelial growth factor (1 ng/ml) caused an increase in membrane-bound ACE and ACE mRNA levels which was inhibited by pretreatment of the cells with TNF-alpha (1 ng/ml) or IL-1beta (1 ng/ml). In summary, the cytokines TNF-alpha and IL-1beta downregulated ACE in cultured human endothelial cells, which effect was probably mediated by the p38 MAPK pathway. Downregulation of ACE by TNF-alpha and IL-1beta locally in the vascular wall may be a counterbalancing mechanism in inflammatory processes such as atherosclerosis, leading to decreased production of angiotensin II and accumulation of bradykinin.
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PMID:Downregulation of angiotensin-converting enzyme by tumor necrosis factor-alpha and interleukin-1beta in cultured human endothelial cells. 1145 8

Protection of the endothelium, the metabolically active inner lining of the vasculature, appears to be a key factor in maintaining cardiovascular (CV) health. The endothelium responds to hemodynamic and hormonal factors by secreting substances that maintain vascular homeostasis. Damage to the endothelium is an initial step in the development of CV disease. Angiotensin-converting enzyme (ACE) inhibitors, which block the formation of the vasoconstricting substance, angiotensin II, have proved to be a key therapy for hypertension and congestive heart failure. The activity of these agents in enhancing vascular health appears to be a critical factor in their therapeutic effectiveness. Large-scale clinical trials over the past decade have shown that ACE inhibition is an effective therapeutic means of not only prolonging survival and reducing morbidity after acute myocardial infarction, but also reducing all-cause mortality and morbidity in patients at high risk for CV disease, including patients with diabetes. ACE is found in far greater amounts in tissue than in plasma. Studies indicate that ACE inhibitors act at the tissue level to provide long-term cardioprotective effects that include a reduction in the progression of atherosclerosis. An issue to resolve is how much ACE inhibition is needed at the tissue level to reverse or prevent further vascular damage.
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PMID:Angiotensin-converting enzyme inhibition to enhance vascular health--clinical and research models. 1149 7

Angiotensin-converting enzyme (ACE) inhibitors are well established as first-line therapy for patients with left ventricular dysfunction, diabetic patients with hypertension or renal disease, and patients recovering from myocardial infarction. Angiotensin II and bradykinin regulate cellular proliferation, inflammation, and endothelial function, thus playing an important role in the pathogenesis of atherosclerosis. A large body of experimental evidence reporting that ACE inhibitors limit these effects has formed the rationale for major clinical trials of these drugs in the management of atherosclerotic vascular disease. The first trial to be completed demonstrated that ACE inhibition improves the prognosis of patients who have, or are at risk of, atherosclerotic vascular disease, independent of its effects on left ventricular function and hypertension. Expanding the indications for ACE inhibitors is now evidence driven, although the choice of agent for these new indications remains to be determined by further research.
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PMID:Potential indications for angiotensin-converting enzyme inhibitors in atherosclerotic vascular disease. 1183 51

Angiotensin-converting enzyme (ACE) regulates blood pressure and is an important target in the management of hypertension. Hypertension is a gender biased disease. Plasma ACE activity is significantly higher in male mice (309 U/l) than female mice (237 U/l) and is reduced significantly upon gonadectomy to 224 and 209 U/l, respectively. Although, the gonads influence plasma ACE activity in both male and female mice, the effect is more pronounced in male mice. Plasma ACE is derived from the cleavage of tissue ACE and lung has the highest concentration of tissue ACE. However, lung ACE activity is not gender dimorphic but increases significantly upon gonadectomy in both male and female. ACE mRNA level in the lung is not influenced by gender or gondaectomy. Therefore, the gonads affect plasma ACE activity by influencing cleavage of tissue ACE to plasma ACE and/or decrease stability of plasma ACE in gonadectomized mice is mediated.
Atherosclerosis 2002 Feb
PMID:Gonadal effects on plasma ACE activity in mice. 1184 53

Angiotensin-converting enzyme inhibitors (ACEi) reduce cardiovascular morbidity and mortality by improving coronary perfusion, reducing ventricular hypertrophy and remodeling, and preventing progression of coronary atherosclerosis. However, the cellular mechanisms underlying the beneficial effects of ACEi are not fully understood. We studied the in vivo effects of ACE inhibition with perindopril on cellular expression of ACE, AT(1) receptors and 2 nitric oxide synthase (NOS) isoforms, endothelial (eNOS) and inducible NOS (iNOS), in human blood vessels using quantitative in vitro autoradiography and immunocytochemistry. Seven patients with ischemic heart disease were treated with perindopril (4 mg/d) for up to 5 weeks before elective coronary bypass surgery, whereas controls did not receive the ACEi (n=7). Perindopril decreased plasma ACE by 70% and the plasma angiotensin II to angiotensin I ratio by 57% and reduced vascular ACE to approximately 65% of control levels in both endothelium and adventitia. By contrast, AT(1) receptor binding in vascular smooth muscle cells was increased by 80% in patients treated with perindopril as confirmed by immunocytochemistry. eNOS was expressed primarily in endothelial cells, whereas little iNOS expression occurred in vascular smooth muscle cells of untreated patients. Both eNOS and iNOS expression seemed to increase during perindopril treatment. These results suggest that suppression of angiotensin II formation in the vascular wall and increased expression of eNOS and iNOS during ACE inhibition may be beneficial in reversing endothelial dysfunction in patients with cardiovascular disease. Because vascular AT(1) receptor expression is increased during chronic ACE inhibition, more clinical studies are required to determine whether it is necessary to combine ACE inhibitors and AT(1) receptor antagonists in clinical management of heart failure, coronary heart disease, and hypertension
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PMID:Perindopril alters vascular angiotensin-converting enzyme, AT(1) receptor, and nitric oxide synthase expression in patients with coronary heart disease. 1236 66

Angiotensin-converting enzyme insertion/deletion (I/D) gene polymorphism plays a role in determining the inter-individual variability of circulating angiotensin-converting enzyme activity and intracellular angiotensin-converting enzyme levels. Angiotensin-converting enzyme, as a key enzyme in the renin-angiotensin system, catalyzes the activation of the vasoconstricting and proliferation-stimulating angiotensin II and breaks down the vasodilatory peptide bradykinin. It is assumed that the excess supply of angiotensin II (due to the deletion polymorphism of the angiotensin-converting enzyme gene) contributes to endothelial dysfunction and in this way promotes the onset and progression of atherosclerosis. The aim of this study was to test whether the presence of the deletion allele of the angiotensin-converting enzyme gene predisposes a more rapid systemic progression of a preexisting peripheral arterial disease. To this end, the course of disease was surveyed for an average of 5 years in 97 patients who were angiotensin-converting enzyme gene-typed and suffered from a stable stage II peripheral arterial disease according to Fontaine. These patients did not suffer from an additional coronary artery disease, a cerebrovascular disease, or other serious illness. A local progression in the periphery or a systemic progression in the coronary or cerebrovascular areas was regarded as study endpoints. Of the patients, 49.5% showed an atherosclerosis progression during the surveillance period. With II-carriers, a progression was registered in 42.1% and with DD carriers, progression was seen in 59.4%. D/I allele frequencies were seen in patients with progression at a level of 0.60/0.40 vs 0.55/0.45 for patients without progression. The average duration of disease in stable stage II (before progression appeared) amounted to 108 +/- 14 months for II carriers, 88 +/- 8 months for ID carriers, and 92 +/- 11 months for DD carriers (p = 0.21). Based on these findings, the deletion polymorphism of the angiotensin-converting enzyme gene is not an independent risk factor for progression of atherosclerosis in patients with peripheral arterial disease.
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PMID:Progression of atherosclerosis in patients with peripheral arterial disease as a function of angiotensin-converting enzyme gene insertion/deletion polymorphism. 1214 41

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) effectively interfere with the renin-angiotensin system and exert various beneficial actions on cardiac and vascular structure and function, beyond their blood pressure-lowering effects. Randomized, controlled clinical trials have shown that ACE inhibitors improve endothelial function, cardiac and vascular remodeling, retard the anatomic progression of atherosclerosis, and reduce the risk of myocardial infarction, stroke, and cardiovascular death. Therefore, these agents are recommended in the treatment of a wide range of patients at risk for adverse cardiovascular outcomes, including those with coronary disease, prior stroke, peripheral arterial disease, high-risk diabetes, hypertension, and heart failure. ARBs are effective blood pressure- lowering and renoprotective agents and can be used in heart failure in patients who do not tolerate ACE inhibitors. The role of ARBs in the prevention of atherosclerosis and its sequelae is currently under investigation. The use of combined ACE inhibitor plus ARB therapy offers theoretical advantages over the use of each of these agents alone and is also under investigation in large, randomized clinical trials.
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PMID:Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in atherosclerosis. 1216 36


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