CLINICAL STUDIES
Lipoprotein(a) and inflammation in human coronary atheroma: association with the severity of clinical presentation
George Dangas, MD*  ,
Roxana Mehran, MD,
Peter C. Harpel, MD*  ,
Samin K. Sharma, MD, FACC* ,
Santica M. Marcovina, PhD||,
Geoffrey Dube, BS*  ,
John A. Ambrose, MD, FACC* and
John T. Fallon, MD, PhD*
* Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York, USA
Department of Medicine (Division of Hematology), Mount Sinai School of Medicine, New York, New York, USA
Department of Pathology, Mount Sinai School of Medicine, New York, New York, USA
Cardiology Research Foundation, Washington Hospital Center, Washington, D.C., USA
|| Department of Medicine, Northwest Lipid Research Laboratories, University of Washington, Seattle, Washington, USA
Manuscript received April 28, 1998;
revised manuscript received July 31, 1998,
accepted August 6, 1998.
Address for correspondence: Dr. John T. Fallon, Cardiovascular Institute, Box 1194, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, New York 10029
fallon{at}vader.mssm.edu
Objectives. The purpose of this study was the investigation of the in vivo role of lipoprotein(a) [Lp(a)] and inflammatory infiltrates in the human coronary atherosclerotic plaque and their correlation with the clinical syndrome of presentation.
Background. Lipoprotein(a) is an atherogenic and thrombogenic lipoprotein, and has been implicated in the pathogenesis of acute coronary syndromes. Lipoprotein(a) induces monocyte chemoattraction and smooth muscle cell activation in vitro. Macrophage infiltration is considered one of the mechanisms of plaque rupture.
Methods. This study of atherectomy specimens investigated the in vivo role of Lp(a) at different stages of the atherogenic process, and its relationship with macrophage infiltration. We examined coronary atheroma removed from 72 patients with stable or unstable angina. Specimens were stained with antibodies specific for Lp(a), macrophages (KP-1), and smooth muscle cells (alpha-actin). Morphometric analysis was used to quantify the plaque areas occupied by each of the three antigens, and their colocalization.
Results. All specimens had localized Lp(a) staining; the mean fractional area was 58.2%. Ninety percent of the macrophage areas colocalized with Lp(a) positive areas, whereas 31.3% of the smooth muscle cell areas colocalized with Lp(a) positive areas. Patients with unstable angina (n = 46) had specimens with larger mean plaque Lp(a) areas than specimens from stable angina patients (n = 26): 64.4% versus 47.7% (p = 0.004). Unstable angina patients with rest pain (n = 28) had greater mean plaque Lp(a) area than unstable angina patients with crescendo exertional pain (n = 18): 71.1% versus 52.4% (p < 0.001). Mean KP-1 area was 31.2% in unstable rest angina versus 18.3% in stable angina (p = 0.05); alpha-actin area was greater in stable (48.5%) and crescendo exertional angina (48.8%) than in rest angina (30.4%). The strongest correlation between plaque KP-1 and Lp(a) area was in unstable rest angina (r = 0.88, p < 0.001), and between alpha-actin and Lp(a) areas in the crescendo exertional angina (r = 0.62, p < 0.01).
Conclusions. Lipoprotein(a) is ubiquitous in human coronary atheroma. It is detected in larger amounts in tissue from culprit lesions in patients with unstable compared to stable syndromes, and has significant colocalization with plaque macrophages. A correlation of plaque alpha-actin and Lp(a) area suggests a role of Lp(a) in plaque growth.
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Abbreviations and Acronyms
| | apo(a) | = apoprotein(a) | | DCA | = directional coronary atherectomy | | Lp(a) | = lipoprotein(a) | | TGF-beta | = transforming growth factor-beta | | VLDL | = very low density lipoprotein |
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