Arteriosclerosis, thrombosis, and vascular biology
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Arterioscler. Thromb. Vasc. Biol. · Nov 1997
Comparative StudyRole of angiotensin II and bradykinin on aortic collagen following converting enzyme inhibition in spontaneously hypertensive rats.
We previously showed that chronic angiotensin-converting enzyme (ACE) inhibition prevented the increase in aortic collagen in spontaneously hypertensive rats (SHRs) independently of blood pressure reduction. The aim of the present study was to determine whether the effects of ACE inhibition on aortic fibrosis were due to inhibition of angiotensin II formation, preservation of bradykinin, or a combination of both. Four week-old SHRs were treated for 4 months with the ACE inhibitor quinapril, quinapril with the bradykinin B2 receptor antagonist Hoe 140, or the angiotensin II AT1 receptor antagonist CI996. ⋯ In relation with blood pressure changes, aortic hypertrophy was significantly prevented by quinapril but not by quinapril-Hoe 140 or CI996. In contrast, aortic collagen accumulation was completely prevented by all three treatments. The study provides evidence that in young live SHRs, the prevention of aortic collagen accumulation is independent of blood pressure changes and bradykinin preservation and involves exclusively angiotensin II inhibition through AT1 receptors.
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Arterioscler. Thromb. Vasc. Biol. · Nov 1997
Randomized Controlled Trial Comparative Study Clinical TrialSoluble vascular cell adhesion molecule-1 as a biohumoral correlate of atherosclerosis.
Vascular cell adhesion molecule-1 (VCAM-1) is a protein expressed on the surface of activated endothelial cells and expressed in early atherosclerosis. Because part of the protein is shed in the circulation and can be detected in peripheral plasma [soluble (s) VCAM-1], we hypothesized that sVCAM-1 may be a circulating marker of the presence and severity of atherosclerosis in humans. We selected 11 patients with essential hypertension plus peripheral vascular disease (PVD) and matched them for age, gender, body mass index, and smoking habits with 11 patients with uncomplicated essential hypertension (UH) and 11 healthy controls. ⋯ Because many of the biohumoral variables assessed were mutually intercorrelated, they were entered in a multivariate analysis to assess their contribution in explaining IMTmax variability. sVCAM-1 remained the only independent predictor of IMTmax and totally abolished the contribution of other variables to IMTmax variability. Thus, sVCAM-1 is a good biohumoral correlate of overt atherosclerosis, independent of underlying hypertension, and may be an in vivo marker of endothelial activation. Its potential value as a surrogate for global risk assessment and its behavior in intervention studies remain to be determined.
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Arterioscler. Thromb. Vasc. Biol. · Jun 1996
Multicenter Study Comparative StudyThrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency. A cooperative, retrospective study. Gesellschaft fur Thrombose- und Hamostaseforschung (GTH) Study Group on Natural Inhibitors.
A cooperative, retrospective study was performed on data from 8 coagulation laboratories and thrombosis units in Austria, Germany, and Switzerland to assess the risk for thrombosis in patients with hereditary antithrombin III (AT-III), protein C (PC), and protein S (PS) deficiencies; to compare the clinical manifestations of these 3 deficiency states; and to estimate the risk for development of thrombosis in high-risk situations. Two hundred thirty patients from 71 families with a documented hereditary deficiency of a natural coagulation inhibitor were included in the study. The patient group comprised 69 patients from 25 families with AT-III deficiency, 86 patients from 27 families with PC deficiency, and 75 patients from 19 families with PS deficiency. ⋯ We conclude that diagnosis of a coagulation inhibitor deficiency state should be made before 14 years of age. During childhood thrombosis prophylaxis cannot be regularly recommended but should be instituted after 13 years of age during/after abdominal surgery, including appendectomy, and after leg injury in AT-III-, PC-, and PS-deficient patients. The high recurrence rate (60% spontaneous recurrence) and the relatively high frequency of mesenteric vein thrombosis as a recurrent event favor introduction of long-term oral anticoagulant treatment after the first thrombotic event in patients with a documented hereditary deficiency of AT-III, PC, or PS.