Rat arterial wall retains myointimal hyperplastic potential long after arterial injury.
BACKGROUND
Many novel molecular and pharmacological modalities have been proposed for the treatment of accelerated vascular diseases. Yet the fundamental question remains of whether the vessel wall can be treated once only or whether single-dose therapy simply delays the inevitable processes that lead to intimal hyperplasia. Since platelet adhesion and aggregation are critical events in vascular healing, we sought to determine whether the injured blood vessel would retain its myointimal potential after reversal of even prolonged periods of thrombocytopenia.


RESULTS
A novel nonimmune method sustained thrombocytopenia and suppressed postinjury neointimal hyperplasia by 88%. Infusion of fresh platelets, even 14 days after initial denuding injury, restored the full neointimal hyperplastic potential. Platelet depletion presumably removed factors chemotactic for vascular smooth muscle cells but had no effect on the overexpression of the platelet-derived growth factor receptor-beta (PDGFR-beta) subunit after vascular injury. In native vessels, 26.5+/-2.5% of medial smooth muscle cells expressed PDGFR-beta. In all animals, medial PDGFR-beta expression doubled 2 weeks after endothelial denudation and was evident in up to 74.5+/-2.5% of the cells forming the neointima.


CONCLUSIONS
Thus, though the hyperplastic potential of the injured blood vessel can be delayed with removal of growth stimuli, it is not lost forever, and if the media is not made quiescent, neointimal hyperplasia is simply delayed rather than prevented. These results may have a profound effect on our understanding and treatment of accelerated proliferative vascular diseases.
Sirois
M G
MG
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, USA.
Simons
M
M
Kuter
D J
DJ
Rosenberg
R D
RD
Edelman
E R
ER
D000818:Animals; D002066:Busulfan / Q000494:pharmacology* / Q000627:therapeutic use; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology; D016893:Carotid Stenosis / Q000517:prevention & control*; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D008297:Male; D017713:Platelet Transfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000187:drug effects; D012008:Recurrence; D013921:Thrombocytopenia / Q000139:chemically induced; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology*
D017479:Receptors, Platelet-Derived Growth Factor; D002066:Busulfan