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.
OBJECTIVE
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.
Sangiorgi
Giuseppe
G
Department of Cardiovascular Disease, Istituto Policlinico San Donato, San Donato Milanese, Milan, Italy. sangiorgi@emocolumbus.it
Mauriello
Alessandro
A
Bonanno
Elena
E
Oxvig
Claus
C
Conover
Cheryl A
CA
Christiansen
Michael
M
Trimarchi
Santi
S
Rampoldi
Vincenzo
V
Holmes
David R
DR
Schwartz
Robert S
RS
Spagnoli
Luigi Giusto
LG
D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A