Plasma levels of metalloproteinases-9 and -2 in the acute and subacute phases of type A and type B aortic dissection.
OBJECTIVE
Aortic dissection is characterized by an acute phase of medial dissection and a subacute-chronic phase of vessel wall repair. Matrix metalloproteinases (MMPs), through degradation of extracellular matrix, may play an important role in these processes. Elevation of MMPs might represent an opportunity to diagnostically characterize acute or chronic aortic processes. We examined the potential diagnostic role of MMP-9 and MMP-2 in different phases of aortic dissection.


METHODS
Plasma levels of MMPs were evaluated by enzyme-linked immunosorbent assay technique in 13 patients affected by acute aortic dissection (nine type A, four type B). Ten healthy subjects were used as controls. In patients with type B aortic dissection treated medically, plasma curves (1, 3, 6, 12, 24, 48 and 96 h; 1 and 2 weeks; and 2 months from symptom onset) were also assessed. Aortic tissue samples obtained during surgery were evaluated by immunohistochemistry and western blot for MM-9 and tissue inhibitor of metalloproteinase-1 expression.


RESULTS
MMP-9 plasma levels were increased in patients affected by type A and type B aortic dissection presenting within 1 h from onset of symptoms compared to controls (29.3 +/- 16.1 and 16.7 +/- 2.1 ng/ml versus 7.74 +/- 1.6 ng/ml, P < 0.03, respectively). No differences were detected in MMP-2 plasma levels compared to controls (4.84 +/- 1.2 ng/ml for type A and 6.16 +/- 0.6 ng/ml versus 3.17 +/- 1.0 ng/ml for controls, P = NS, respectively). In type B aortic dissection, mean MMP-9 plasma levels increased significantly from hospital admission to 2-month follow-up (16.7 +/- 2.1 ng/ml versus 58.0 +/- 8.2 ng/ml, P < 0.0001). Conversely, no difference in MMP-2 plasma levels was evident during follow-up (6.16 +/- 0.6 ng/ml versus 4.28 +/- 0.4 ng/ml, P = NS, respectively). Low-moderate (+/++) expression of MMP-9 was evident at immunohistochemistry in the acute phase whereas a marked expression (++++) was detected in the subacute phase.


CONCLUSIONS
This pilot study suggests that the acute and subacute phase of both type A and type B aortic dissection is characterized by an increase of MMP-9 plasma levels. A marked increase is also evident in the subacute phase of medically treated type B aortic dissection as an expression of aortic wall remodelling. An increase of proteolytic activity could accompany attempts of the dissected aorta to heal itself but such a phenomena might further weaken the aortic wall, predisposing it to dilation and/or rupture.
Sangiorgi
Giuseppe
G
Department of Cardiovascular Diseases, Istituto Policlinico San Donato, University of Milan, Milan, Italy. sangiorgi@emocolumbus.it
Trimarchi
Santi
S
Mauriello
Alessandro
A
Righini
Paolo
P
Bossone
Eduardo
E
Suzuki
Toru
T
Rampoldi
Vincenzo
V
Eagle
Kim A
KA
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000784:Aortic Dissection / Q000201:enzymology* / Q000601:surgery; D001014:Aortic Aneurysm / Q000201:enzymology* / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000097:blood*; D008875:Middle Aged; D012107:Research Design; D012720:Severity of Illness Index; D013997:Time Factors; D014656:Vascular Surgical Procedures
D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9