Endovascular treatment of aneurysms: gene expression of neointimal cells recruited on the embolic agent and evolution with recurrence in an experimental model.
OBJECTIVE
The authors attempted to identify genes associated with healing or recurrence after embolization in an aneurysm model in which neointima formation at the neck varies according to flow zones. A better understanding of the relationship between blood flow, molecular events, and healing or recurrence may provide future avenues to improve results of endovascular treatment of aneurysms.


METHODS
Bilateral carotid venous pouch aneurysms were constructed in 36 dogs and embolized with gelatin sponges. Angiography and pathological studies were performed at T0 and/or 3 weeks (n=22). Angiographic results and neointima formation were scored using a qualitative index applied to the distal (inflow) and proximal (outflow) zones of the neck. In 14 animals, mRNA expression 1 to 14 days after embolization at the proximal or distal segment of the sponge was analyzed by RT-PCR, attempting to correlate flow zones, gene expression, and neointima formation.


RESULTS
Aneurysms recurred at 3 weeks, as shown by significantly worse angiographic scores as compared to T0 (P<.01). Neointimal scores differed at pathology, with a more complete neointima at the proximal as compared to the distal aspect of the sponge at 3 weeks (P=.027). Embolization was followed by migration of CD31+, CD14+, smooth muscle alpha-actin+ (SMA+) cells that progressively expressed metalloproteinases (MMP-9,-12,-14), but stable or lesser, retarded expression of inhibitors (TIMP1-4). Growth factors (PDGF-BB, TGF-beta1, TNF-alpha, MCP-1 and Ang-1) were expressed at increasing levels, maximal at 7 to 14 days. Differences between distal and proximal zones were limited to increased expression of MMP-2 proximally (P<.035).


CONCLUSIONS
Gene expression after embolization is compatible with patterns associated with neointima formation. The authors have not identified key factors involved in recurrence.
Raymond
Jean
J
CHUM Research Centre-Notre-Dame Hospital, Montreal, Quebec, Canada. dr_jean_raymond@hotmail.com
Ogoudikpe
Christelle
C
Salazkin
Igor
I
Metcalfe
Annick
A
Gevry
Guylaine
G
Chagnon
Miguel
M
Robledo
Olivier
O
D000199:Actins / Q000235:genetics; D000803:Angiotensin I / Q000235:genetics; D000818:Animals; D000077214:Becaplermin; D002533:Cerebral Angiography; D018932:Chemokine CCL2 / Q000235:genetics; D004195:Disease Models, Animal; D004285:Dogs; D004621:Embolization, Therapeutic; D005781:Gelatin Sponge, Absorbable / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D006490:Hemostatics / Q000627:therapeutic use; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging / Q000235:genetics / Q000628:therapy*; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009333:Neck / Q000098:blood supply / Q000000981:diagnostic imaging; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012008:Recurrence; D012039:Regional Blood Flow / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014656:Vascular Surgical Procedures
D000199:Actins; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D006490:Hemostatics; D018950:Lipopolysaccharide Receptors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C508960:TGFB1 protein, human; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000077214:Becaplermin; D000803:Angiotensin I; D020782:Matrix Metalloproteinases