Pregnancy-Associated Plasma Protein-A Is Markedly Expressed by Monocyte-Macrophage Cells in Vulnerable and Ruptured Carotid Atherosclerotic Plaques. A Link Between Inflammation and Cerebrovascular Events

Giuseppe Sangiorgi, Alessandro Mauriello, Elena Bonanno, Claus Oxvig, Cheryl A. Conover, Michael Christiansen, Santi Trimarchi, Vincenzo Rampoldi, David R. Holmes, Robert S. Schwartz, Luigi Giusto Spagnoli

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Objectives: The study aim was to evaluate serologic expression of pregnancy-associated protein-A (PAPP-A) in patients affected by cerebrovascular accidents and to correlate it with histopathologic carotid plaque complexity. Background: Little is known about PAPP-A expression in carotid atherosclerotic disease and whether this protein represents a marker of plaque vulnerability also in carotid district. Methods: Seventy-two carotid plaques from patients submitted to surgical endarterectomy (19 who suffered a major stroke, 24 transient ischemic attack, and 29 asymptomatic) were evaluated. Serologic PAPP-A levels were determined by enzyme-linked immunoadsorbent assay. Plaques were divided in three groups based on histology: 1) stable (n = 38); 2) vulnerable (n = 13); 3) ruptured with thrombus (n = 14). Immunohistochemical staining for PAPP-A, smooth muscle cells, macrophages, and T-lymphocytes was performed in all cases. Real-time polymerase chain reaction assessed local PAPP-A production, and double immunofluorescence confocal microscopy (ICM) characterized cell type expressing PAPP-A. Results: Pregnancy-associated protein-A (serologic values were 4.02 ± 0.18 mIU/l in Group 1, 7.43 ± 0.97 mIU/l in Group 2, and 6.97 ± 0.75 mIU/l in Group 3 [1 vs. 3, p = 0.01; 1 vs. 2, p = 0.004; 2 vs. 3, p = 0.71, respectively]). Pregnancy-associated protein-A (expression showed a mean score value of 0.62 ± 0.06 for stable plaques, 2.54 ± 0.14 for vulnerable plaques, and 2.71 ± 0.12 for ruptured plaques [1 vs. 2, p = 0.001; 1 vs. 3, p = 0.001; 2 vs. 3, p = 0.37, respectively]). Real-time polymerase chain reaction demonstrated local messenger ribonucleic acid PAPP-A production, and double ICM confirmed monocyte/macrophage expression of PAPP-A in Groups 2 and 3 but not Group 1. Conclusions: This study suggests that PAPP-A is a marker of carotid plaque destabilization and rupture. Further studies are necessary to determine if PAPP-A can represents a new target for stratifying the risk of cerebrovascular events.

Original languageEnglish (US)
Pages (from-to)2201-2211
Number of pages11
JournalJournal of the American College of Cardiology
Issue number11
StatePublished - Jun 6 2006


ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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