Key result
Coronary adventitial fibroblasts tracked with BrdU contributed negligibly to neointima formation following balloon angioplasty in swine (0.65% and 1.7% of neointimal cells on day 25).
Coronary adventitial fibroblasts contribute negligibly to neointima formation after balloon angioplasty in a swine model, suggesting the neointima is primarily of smooth muscle cell origin.
Negligible adventitial fibroblast contribution cautions against targeting them post-angioplasty; leaves open smooth muscle cell origins in human restenosis.
Adventitial fibroblasts have previously been proposed to be a major constituent of the neointima following coronary balloon angioplasty. The present study utilized the bromodeoxyuridine (BrdU) pulse-chase technique to track adventitial fibroblast migration early after balloon injury in swine. BrdU (30 mg/kg), a marker of proliferating cells, was given intravenously 1 or 2 days after balloon angioplasty. For each time point, one animal was euthanized 24 h after injection to identify the location of the proliferating cells, while a second animal was euthanized 25 days after angioplasty to determine whether the proliferating cells migrated to form the neointima. Our results demonstrate that BrdU-positive cells were located primarily in the adventitia with all three time points 24 h after balloon angioplasty. Furthermore, when BrdU was injected on day 1 or 2 only 0.65 +/- 0.17% and 1.7 +/- 0.64%, respectively, of neointimal cells were BrdU positive on day 25. In conclusion, these results demonstrate a negligible contribution of coronary adventitial fibroblasts to neointima formation following coronary balloon angioplasty, supporting the concept that the neointima is primarily of smooth muscle cell origin.
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Fleenor et al. (2009) studied Neointimal formation following coronary balloon angioplasty. Bromodeoxyuridine (BrdU) was evaluated on Percentage of neointimal cells that were BrdU positive on day 25. Coronary adventitial fibroblasts tracked with BrdU contributed negligibly to neointima formation following balloon angioplasty in swine (0.65% and 1.7% of neointimal cells on day 25).
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