Published online before print October 25, 2004, doi: 10.1161/01.CIR.0000146787.16297.E8
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(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
This article has been cited by other articles:
 |
|
 |
|
  S. Coli, M. Magnoni, G. Sangiorgi, M. M. Marrocco-Trischitta, G. Melisurgo, A. Mauriello, L. Spagnoli, R. Chiesa, D. Cianflone, and A. Maseri Contrast-enhanced ultrasound imaging of intraplaque neovascularization in carotid arteries correlation with histology and plaque echogenicity. J. Am. Coll. Cardiol., July 15, 2008; 52(3): 223 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Kern and J. Narula Looking Into the Vessel: The More You See, the More You Want to See J. Am. Coll. Cardiol. Img., July 1, 2008; 1(4): 556 - 559. [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Wasserman, A. R. Sharrett, S. Lai, A. S. Gomes, M. Cushman, A. R. Folsom, D. E. Bild, R. A. Kronmal, S. Sinha, and D. A. Bluemke Risk Factor Associations With the Presence of a Lipid Core in Carotid Plaque of Asymptomatic Individuals Using High-Resolution MRI: The Multi-Ethnic Study of Atherosclerosis (MESA) Stroke, February 1, 2008; 39(2): 329 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Shah, P. Balan, M. Weinberg, V. Reddy, R. Neems, M. Feinstein, J. Dainauskas, P. Meyer, M. Goldin, and S. B. Feinstein Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vascular Medicine, November 1, 2007; 12(4): 291 - 297. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Tichelli, C. Bucher, A. Rovo, G. Stussi, M. Stern, M. Paulussen, J. Halter, S. Meyer-Monard, D. Heim, D. A. Tsakiris, et al. Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation Blood, November 1, 2007; 110(9): 3463 - 3471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ebeling Barbier, T. Bjerner, T. Hansen, J. Andersson, L. Lind, J. Hulthe, L. Johansson, and H. Ahlstrom Clinically Unrecognized Myocardial Infarction Detected at MR Imaging May Not Be Associated with Atherosclerosis Radiology, October 1, 2007; 245(1): 103 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Vicenzini, M. F. Giannoni, F. Puccinelli, M. C. Ricciardi, M. Altieri, V. Di Piero, B. Gossetti, F. Benedetti Valentini, and G. L. Lenzi Detection of Carotid Adventitial Vasa Vasorum and Plaque Vascularization With Ultrasound Cadence Contrast Pulse Sequencing Technique and Echo-Contrast Agent Stroke, October 1, 2007; 38(10): 2841 - 2843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Levy, K. R. Purushothaman, N. S. Levy, M. Purushothaman, M. Strauss, R. Asleh, S. Marsh, O. Cohen, S. K. Moestrup, H. J. Moller, et al. Downregulation of the Hemoglobin Scavenger Receptor in Individuals With Diabetes and the Hp 2-2 Genotype: Implications for the Response to Intraplaque Hemorrhage and Plaque Vulnerability Circ. Res., July 6, 2007; 101(1): 106 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Herrmann and A. Lerman Atherosclerosis in the Back Yard J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2102 - 2104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Doyle and N. Caplice Plaque Neovascularization and Antiangiogenic Therapy for Atherosclerosis J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2073 - 2080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Saloner, G. Acevedo-Bolton, M. Wintermark, and J. H. Rapp MRI of Geometric and Compositional Features of Vulnerable Carotid Plaque Stroke, February 1, 2007; 38(2): 637 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sato and H. Sonoda The Vasohibin Family: A Negative Regulatory System of Angiogenesis Genetically Programmed in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 37 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Herrmann, L. O. Lerman, D. Mukhopadhyay, C. Napoli, and A. Lerman Angiogenesis in Atherogenesis Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 1948 - 1957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Feinstein Contrast Ultrasound Imaging of the Carotid Artery Vasa Vasorum and Atherosclerotic Plaque Neovascularization J. Am. Coll. Cardiol., July 18, 2006; 48(2): 236 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.N.E. Redgrave, J.K. Lovett, P.J. Gallagher, and P.M. Rothwell Histological Assessment of 526 Symptomatic Carotid Plaques in Relation to the Nature and Timing of Ischemic Symptoms: The Oxford Plaque Study Circulation, May 16, 2006; 113(19): 2320 - 2328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Momiyama, R. Kato, Z. A. Fayad, N. Tanaka, H. Taniguchi, R. Ohmori, T. Kihara, A. Kameyama, K. Miyazaki, K. Kimura, et al. A Possible Association Between Coronary Plaque Instability and Complex Plaques in Abdominal Aorta Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 903 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wyler von Ballmoos, D. Dubler, M. Mirlacher, G. Cathomas, J. Muser, and B. C. Biedermann Increased Apolipoprotein Deposits in Early Atherosclerotic Lesions Distinguish Symptomatic From Asymptomatic Patients Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 359 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nighoghossian, L. Derex, and P. Douek The Vulnerable Carotid Artery Plaque: Current Imaging Methods and New Perspectives Stroke, December 1, 2005; 36(12): 2764 - 2772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Wasserman, R. J. Wityk, H. H. Trout III, and R. Virmani Low-Grade Carotid Stenosis: Looking Beyond the Lumen With MRI Stroke, November 1, 2005; 36(11): 2504 - 2513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Virmani, F. D. Kolodgie, A. P. Burke, A. V. Finn, H. K. Gold, T. N. Tulenko, S. P. Wrenn, and J. Narula Atherosclerotic Plaque Progression and Vulnerability to Rupture: Angiogenesis as a Source of Intraplaque Hemorrhage Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2054 - 2061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster, P. R. Moreno, Z. A. Fayad, R. Corti, and J. J. Badimon Atherothrombosis and High-Risk Plaque: Part I: Evolving Concepts J. Am. Coll. Cardiol., September 20, 2005; 46(6): 937 - 954. [Abstract] [Full Text] [PDF]
|
|