November 12, 1996Open Access
Separation of the arterial wall from blood contact using hydrogel barriers reduces intimal thickening after balloon injury in the rat: The roles of medial and luminal factors in arterial healing
Key Result
Blockade of postinjury arterial contact with blood using a nondegradable hydrogel barrier reduced intimal thickening by 95% compared to untreated controls at 14 days.
Structured PICO
Does a hydrogel barrier blocking blood contact reduce intimal thickening after balloon injury in the rat carotid artery?
P
Population
Rat model of balloon-induced injury of the carotid artery
I
Intervention
20-microns thick hydrogel barrier applied to the arterial wall to block thrombus deposition
O
Outcome
Thrombosis, bFGF mobilization, medial repopulation, and intimal thickeningsurrogate
Blocking blood contact with the arterial wall using a hydrogel barrier after balloon injury prevents thrombosis and inhibits intimal thickening, suggesting a luminally derived factor is required for these processes.
Main Result
Effect estimate: 95% reduction
Absolute Event Rate: 0.05% vs 0.92%
p-value: p=<0.001
Limitations
- The injury model used in the rat is more severe than clinical balloon angioplasty.
- The adventitia was removed from the arterial wall, unlike in clinical cases.
- Lack of an underlying vascular disease makes clinical extrapolation difficult.
Abstract
The objective of this study was to clarify the relative roles of medial versus luminal factors in the induction of thickening of the arterial intima after balloon angioplasty injury. Platelet-derived growth factor (PDGF) and thrombin, both associated with thrombosis, and basic fibroblast growth factor (bFGF), stored in the arterial wall, have been implicated in this process. To unequivocally isolate the media from luminally derived factors, we used a 20-microns thick hydrogel barrier that adhered firmly to the arterial wall to block thrombus deposition after balloon-induced injury of the carotid artery of the rat. Thrombosis, bFGF mobilization, medial repopulation, and intimal thickening were measured. Blockade of postinjury arterial contact with blood prevented thrombosis and dramatically inhibited both intimal thickening and endogenous bFGF mobilization. By blocking blood contact on the two time scales of thrombosis and of intimal thickening, and by using local protein release to probe, by reconstitution, the individual roles of PDGF-BB and thrombin, we were able to conclude that a luminally derived factor other than PDGF or thrombin is required for the initiation of cellular events leading to intimal thickening after balloon injury in the rat. We further conclude that a luminally derived factor is required for mobilization of medial bFGF.