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 Holmes, Robert S. Schwartz, Luigi Giusto Spagnoli

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Abstract

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
Volume47
Issue number11
DOIs
StatePublished - Jun 6 2006

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Pregnancy-Associated Plasma Protein-A
Atherosclerotic Plaques
Monocytes
Macrophages
Inflammation
Pregnancy Proteins
Staphylococcal Protein A
Fluorescence Microscopy
Confocal Microscopy
Real-Time Polymerase Chain Reaction
Stroke
Immunosorbents
Endarterectomy
Carotid Artery Diseases
Transient Ischemic Attack
Smooth Muscle Myocytes
Rupture
Histology
Thrombosis

ASJC Scopus subject areas

  • Nursing(all)

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

In: Journal of the American College of Cardiology, Vol. 47, No. 11, 06.06.2006, p. 2201-2211.

Research output: Contribution to journalArticle

Sangiorgi, Giuseppe ; Mauriello, Alessandro ; Bonanno, Elena ; Oxvig, Claus ; Conover, Cheryl A ; Christiansen, Michael ; Trimarchi, Santi ; Rampoldi, Vincenzo ; Holmes, David ; Schwartz, Robert S. ; Spagnoli, Luigi Giusto. / 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. In: Journal of the American College of Cardiology. 2006 ; Vol. 47, No. 11. pp. 2201-2211.
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title = "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",
abstract = "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.",
author = "Giuseppe Sangiorgi and Alessandro Mauriello and Elena Bonanno and Claus Oxvig and Conover, {Cheryl A} and Michael Christiansen and Santi Trimarchi and Vincenzo Rampoldi and David Holmes and Schwartz, {Robert S.} and Spagnoli, {Luigi Giusto}",
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T1 - 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

AU - Sangiorgi, Giuseppe

AU - Mauriello, Alessandro

AU - Bonanno, Elena

AU - Oxvig, Claus

AU - Conover, Cheryl A

AU - Christiansen, Michael

AU - Trimarchi, Santi

AU - Rampoldi, Vincenzo

AU - Holmes, David

AU - Schwartz, Robert S.

AU - Spagnoli, Luigi Giusto

PY - 2006/6/6

Y1 - 2006/6/6

N2 - 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.

AB - 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.

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