Intimomedial Interface Damage and Adventitial Inflammation Is Increased Beneath Disrupted Atherosclerosis in the Aorta: Implications for Plaque Vulnerability

Background—Atherosclerotic plaque progression is frequently accompanied by compensatory enlargement to preserve the lumen. These enlarging plaques develop features of vulnerability, however, leading to disruption and lumen obstruction. This complex transition from compensatory expansion to plaque disruption may not derive solely from progressive intimal disease. Concurrent changes at the intimomedial interface and within the tunica media and adventitia may play a role in plaque instability. We tested this hypothesis by investigating whether interface changes, including internal elastic lamina (IEL) rupture, and medial and adventitial changes, including inflammation, fibrosis, and atrophy, more frequently accompany disrupted than nondisrupted atherosclerotic plaques. Methods and Results—Computerized planimetry and ocular micrometry were used for systematic quantification of intimal, medial, and adventitial histopathological features in 598 human aortic plaques according to the AHA classification. Disrupted plaques exhibited larger plaque and lipid pool areas (P =0.0001) and a higher incidence of rupture of the IEL (P =0.0001). Medial and adventitial inflammation (P =0.01), medial fibrosis (P =0.0001), and medial atrophy (P =0.0001) were also higher in disrupted plaques. Furthermore, medial thickness was reduced in disrupted plaques (P =0.0001). Logistic regression analysis identified rupture of the IEL as an independent predictor for fibrous cap disruption (P =0.0001). Conclusions—Compared with nondisrupted plaques, disrupted plaques have an increased incidence of IEL rupture, medial and adventitial inflammation, medial fibrosis, and medial atrophy. These intimomedial interface and adventitial changes may play a role in the natural history of complex atherosclerotic lesions. The interaction between medial and adventitial pathology and the intimal atherosclerotic process deserves further investigation.

[1]  R. Kamm,et al.  Distribution of Circumferential Stress in Ruptured and Stable Atherosclerotic Lesions A Structural Analysis With Histopathological Correlation , 1993, Circulation.

[2]  S. Glagov,et al.  Transmural Organization of the Arterial Media: The Lamellar Unit Revisited , 1985, Arteriosclerosis.

[3]  A. Becker,et al.  Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization? , 1999, Cardiovascular research.

[4]  P. Libby.  Molecular bases of the acute coronary syndromes. , 1995, Circulation.

[5]  T. Paavonen,et al.  Association between myocardial infarction and the mast cells in the adventitia of the infarct-related coronary artery. , 1999, Circulation.

[6]  R. Virmani,et al.  Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. , 1997, The New England journal of medicine.

[7]  S E Nissen,et al.  Extent and direction of arterial remodeling in stable versus unstable coronary syndromes : an intravascular ultrasound study. , 2000, Circulation.

[8]  E L Ritman,et al.  Adventitial vasa vasorum in balloon-injured coronary arteries: visualization and quantitation by a microscopic three-dimensional computed tomography technique. , 1998, Journal of the American College of Cardiology.

[9]  D. Faxon,et al.  Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). CASS Participating Investigators and Staff. , 1993, Journal of the American College of Cardiology.

[10]  Renu Virmani,et al.  Morphological Predictors of Arterial Remodeling in Coronary Atherosclerosis , 2002, Circulation.

[11]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (1). , 1992, The New England journal of medicine.

[12]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (2). , 1992, The New England journal of medicine.

[13]  M. Nobuyoshi,et al.  Significance of adventitial inflammation of the coronary artery in patients with unstable angina: results at autopsy. , 1985, Circulation.

[14]  S. Oparil,et al.  Direct in vivo evidence demonstrating neointimal migration of adventitial fibroblasts after balloon injury of rat carotid arteries. , 2000, Circulation.

[15]  M. Davies.  Glagovian remodelling, plaque composition, and stenosis generation , 2000, Heart.

[16]  R D Kamm,et al.  Vascular mechanics for the cardiologist. , 1994, Journal of the American College of Cardiology.

[17]  R. Erbel,et al.  Size of emptied plaque cavity following spontaneous rupture is related to coronary dimensions, not to the degree of lumen narrowing. A study with intravascular ultrasound in vivo , 2000, Heart.

[18]  B Hillen,et al.  Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. , 1998, Journal of the American College of Cardiology.

[19]  R D Kamm,et al.  Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. , 1992, Circulation research.

[20]  G. Pasterkamp,et al.  Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery. , 2000, Atherosclerosis.

[21]  T. Noma,et al.  Enhanced Expression of Matrix Metalloproteinase-9 in Abdominal Aortic Aneurysms , 2001, World Journal of Surgery.

[22]  M J Davies,et al.  Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995. , 1996, Circulation.

[23]  V. Fuster,et al.  Angiographic progression of coronary artery disease and the development of myocardial infarction. , 1988, Journal of the American College of Cardiology.

[24]  A Zalewski,et al.  Adventitial remodeling after coronary arterial injury. , 1996, Circulation.

[25]  W. Santamore,et al.  Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? , 1988, Circulation.

[26]  S. Glagov,et al.  A Lamellar Unit of Aortic Medial Structure and Function in Mammals , 1967, Circulation research.

[27]  V. Fuster,et al.  Coronary plaque disruption. , 1995, Circulation.

[28]  C. Zarins,et al.  Compensatory enlargement of human atherosclerotic coronary arteries. , 1987, The New England journal of medicine.

[29]  S Glagov,et al.  Comparison of Abdominal and Thoracic Aortic Medial Structure in Mammals , 1969, Circulation research.

[30]  C. Levene,et al.  Medial thinning in atheroma. , 1953, The Journal of pathology and bacteriology.

[31]  J D Thomas,et al.  Toward the quiescent coronary plaque. , 1993, Journal of the American College of Cardiology.

[32]  W D Wagner,et al.  A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[33]  A. Becker,et al.  The role of inflammation and infection in coronary artery disease. , 2001, Annual review of medicine.

[34]  J. Willerson,et al.  Role of inflammation in coronary plaque disruption. , 1994, Circulation.

[35]  R. Virmani,et al.  Plaque Rupture and Plaque Erosion , 1999, Thrombosis and Haemostasis.

[36]  Davies Mj.  Glagovian remodelling, plaque composition, and stenosis generation. , 2000 .