Pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo.
OBJECTIVE
The fibroblast growth factor (FGF)/FGF receptor system plays an important role in smooth muscle cell (SMC) activation. Long-pentraxin 3 (PTX3) is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 is produced by different cell types of the vessel wall, including SMCs. PTX3 binds FGF2 and inhibits its angiogenic activity on endothelial cells. We investigated the capacity of PTX3 to affect FGF2-dependent SMC activation in vitro and in vivo.


RESULTS
When added to human coronary artery SMCs, human PTX3 inhibits cell proliferation driven by endogenous FGF2 and the mitogenic and chemotactic activity exerted by exogenous recombinant FGF2. Accordingly, PTX3 prevents (125)I-FGF2 interaction with FGF receptors on the same cells. Also, PTX3 overexpression after recombinant adeno-associated virus-PTX3 gene transfer inhibits human coronary artery SMC proliferation and survival promoted by FGF2 in vitro. Consistently, a single local endovascular injection of recombinant adeno-associated virus-PTX3 gene inhibits intimal thickening after balloon injury in rat carotid arteries.


CONCLUSIONS
PTX3 is a potent inhibitor of the autocrine and paracrine stimulation exerted by FGF2 on SMCs. Local PTX3 upregulation may modulate SMC activation after arterial injury.
Camozzi
Maura
M
Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, 25123 Brescia, Italy.
Zacchigna
Serena
S
Rusnati
Marco
M
Coltrini
Daniela
D
Ramirez-Correa
Genaro
G
Bottazzi
Barbara
B
Mantovani
Alberto
A
Giacca
Mauro
M
Presta
Marco
M
D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000493:pharmacokinetics*; D006801:Humans; D006965:Hyperplasia; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014161:Transduction, Genetic; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D016222:Fibroblast Growth Factor 2; D007457:Iodine Radioisotopes; D000683:Serum Amyloid P-Component; D000099153:Pentraxins