Published online before print October 25, 2004, doi: 10.1161/01.CIR.0000146787.16297.E8
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(Circulation. 2004;110:2843-2850.)
© 2004 American Heart Association, Inc.
Coronary Heart Disease |
Arterial Neovascularization and Inflammation in Vulnerable Patients
Early and Late Signs of Symptomatic Atherosclerosis
From the Department of Medicine, University Hospital Bruderholz, Bruderholz, and Department of Research, University Hospital Basel, Basel (M.F., M.K., R.K., B.C.B.); Institute of Pathology, University of Basel, Basel (M.M., G.S.); and Cantonal Institute of Pathology, Liestal (G.C.), Switzerland.
Correspondence to Barbara C. Biedermann, MD, Department of Medicine, University Hospital Bruderholz, CH-4101 Bruderholz, Switzerland. E-mail barbara.biedermann{at}unibas.ch
Received May 5, 2004; revision received August 4, 2004; accepted August 12, 2004.
Background— Atherosclerosis is complicated by cardiovascular events such as myocardial infarction, stroke, or peripheral arterial occlusive disease. Inflammation and pathological neovascularization are thought to precipitate plaque rupture or erosion, both causes of arterial thrombosis and cardiovascular events. We tested the hypothesis that arterial inflammation and angiogenic events are increased throughout the arterial tree in vulnerable patients, ie, in patients who suffered from cardiovascular events, compared with patients who never suffered from complications of atherosclerosis.
Methods and Results— In a postmortem study, we quantified the inflammatory infiltrate and microvascular network in the arterial wall of iliac, carotid, and renal arteries. Tissue microarray technology was adapted to investigate full-thickness arterial sectors. We compared 22 patients with symptomatic atherosclerosis with 27 patients who never had suffered from any cardiovascular event. The absolute intimal macrophage content was 2- to 4-fold higher in vulnerable patients at all 3 arterial sites analyzed (P<0.05). Patients with symptomatic atherosclerosis had a denser network of vasa vasorum than patients with asymptomatic disease (33±2 versus 25±2 adventitial microvessels per 1 mm2; P=0.008). Hyperplasia of vasa vasorum was an early and macrophage infiltration was a late sign of symptomatic atherosclerosis.
Conclusions— High intimal macrophage content and a hyperplastic network of vasa vasorum characterize vulnerable patients suffering from symptomatic atherosclerosis. These changes are uniformly present in different arterial beds and support the concept of symptomatic atherosclerosis as a panarterial disease.
Key Words: arteriosclerosis • inflammation • angiogenesis, pathological • tissue microarray
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