Estrogen enhances vasoconstrictive remodeling after injury in male rabbits.

The complete spectrum of estrogen vascular effects remains unclear. In particular, estrogen effects in the vascular response to profound injury in males have not been explored in detail. Therefore, we submitted 44 male New Zealand rabbits weighing 3.4 +/- 0.6 kg to overdistention balloon injury of the right iliac artery. Rabbits were given 17beta-estradiol (5.45 micromol/day, sc) or vehicle for 7 days before and 14 days after injury, when the arteries were examined by post-mortem histomorphometry. Arteriographic caliber was assessed in vivo at baseline and before sacrifice. On day 14 after injury, in vivo arteriographic caliber (baseline = 2.44 +/- 0.43 mm) was decreased by 23.1 +/- 0.1% in controls and by 44.5 +/- 0.1% in estrogen-treated rabbits (P < 0.001). Neither the neointimal area nor the neointima/media area ratio changed after estrogen treatment. Collagen fraction was increased in the media and neointima of estrogen-treated rabbits vs control (1.38 +/- 1.30 vs 0.35 +/- 0.67, respectively, P = 0.01). Taken together, these findings suggest that estrogen increased negative vascular remodeling. Transcription of endothelial and inducible nitric oxide synthases (eNOS and iNOS) was analyzed by RT-PCR. eNOS mRNA expression was marginally increased after estrogen (P = 0.07) and injury. iNOS mRNA was increased 2- to 3-fold on day 14 after injury. With estrogen treatment, iNOS mRNA increased in uninjured arteries and exhibited a further 5.5-fold increase after injury. We concluded that estrogen increased lumen loss after balloon injury in male rabbits, likely by increased negative remodeling, which may be related to increased iNOS transcriptional rates.

Estrogen enhances vasoconstrictive remodeling after injury in male rabbits

The complete spectrum of estrogen vascular effects remains unclear. In particular, estrogen effects in the vascular response to profound injury in males have not been explored in detail. Therefore, we submitted 44 male New Zealand rabbits weighing 3.4 ± 0.6 kg to overdistention balloon injury of the right iliac artery. Rabbits were given 17ß-estradiol (5.45 æmol/day, sc) or vehicle for 7 days before and 14 days after injury, when the arteries were examined by post-mortem histomorphometry. Arteriographic caliber was assessed in vivo at baseline and before sacrifice. On day 14 after injury, in vivo arteriographic caliber (baseline = 2.44 ± 0.43 mm) was decreased by 23.1 ± 0.1 percent in controls and by 44.5 ± 0.1 percent in estrogen-treated rabbits (P < 0.001). Neither the neointimal area nor the neointima/media area ratio changed after estrogen treatment. Collagen fraction was increased in the media and neointima of estrogen-treated rabbits vs control (1.38 ± 1.30 vs 0.35 ± 0.67, respectively, P = 0.01). Taken together, these findings suggest that estrogen increased negative vascular remodeling. Transcription of endothelial and inducible nitric oxide synthases (eNOS and iNOS) was analyzed by RT-PCR. eNOS mRNA expression was marginally increased after estrogen (P = 0.07) and injury. iNOS mRNA was increased 2- to 3-fold on day 14 after injury. With estrogen treatment, iNOS mRNA increased in uninjured arteries and exhibited a further 5.5-fold increase after injury. We concluded that estrogen increased lumen loss after balloon injury in male rabbits, likely by increased negative remodeling, which may be related to increased iNOS transcriptional rates.

Marked neointimal lipoprotein lipase increase in distinct models of proclivity to atherosclerosis: a feature independent of endothelial layer integrity.

Lipoprotein lipase (LPL) in the arterial wall has been proposed to enhance the retention of apoB-containing lipoproteins, an early event in atherosclerosis. As the neointima is considered the primary site of lipid accumulation in atherogenesis, the arterial expression and location of LPL was investigated in distinct experimental models of neointimal formation in normolipidemic rabbits and rats. Neointima elicited by balloon aortic denudation or raised beneath an anatomically intact endothelial layer by placing a silastic collar around the common carotid artery, both showed a striking LPL immunostaining that mostly co-localized with neointimal smooth muscle cells. Besides, increased LPL protein and mRNA in deendothelialized aortas was demonstrated by Western and Northern blot analysis, respectively, suggesting an enhanced expression of LPL in injured arteries. It was concluded that LPL is increased in neointima developed in either denuded vessels or arteries with a preserved endothelium, a finding which suggests that LPL abundance may be an attribute of the neointima, whatever the stimulus that promotes its formation. On the basis of former evidence concerning the role of LPL in lipid retention, this study provides a possible explanation for the injury-induced vessel susceptibility to atherosclerosis, and the particular proneness of the neointimal layer to lipid accretion.