Tennant Gail M, Wadsworth Roger M, Kennedy Simon
Division of Physiology and Pharmacology, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland, UK.
Atherosclerosis. 2008 May;198(1):57-64. doi: 10.1016/j.atherosclerosis.2007.09.043. Epub 2007 Nov 9.
Activation of PAR-2 in the vasculature affects vascular tone and adhesion of leukocytes to the endothelium. Since adhesion of leukocytes is increased following vascular injury and is important in determining the extent of neointima formation, we hypothesised that mice lacking PAR-2 may have reduced neointima formation following vascular injury. PAR-2 activating peptides and trypsin induced endothelium-dependent relaxation of mouse carotid artery which was absent in the knockout mouse. Lack of a PAR-2 receptor did not affect lymphocyte adhesion under basal conditions, but reduced the contractile response produced by lymphocytes. Twenty-eight days after denuding injury, vessel contraction to lymphocytes was reduced in both strains while lymphocyte adhesion was significantly greater in PAR-2(+/+) mice compared to the PAR-2 knockout mice. Neointimal area was markedly reduced in the PAR-2 knockout mouse. Our data show that PAR-2 modulates inflammatory cell adhesion when stimulated and in mice lacking the PAR-2 receptor, adhesion to injured vessels is reduced with a consequent reduction in neointima formation.
血管中PAR - 2的激活会影响血管张力以及白细胞与内皮的黏附。由于血管损伤后白细胞黏附增加，且在决定新生内膜形成程度方面很重要，我们推测缺乏PAR - 2的小鼠在血管损伤后新生内膜形成可能减少。PAR - 2激活肽和胰蛋白酶可诱导小鼠颈动脉内皮依赖性舒张，而基因敲除小鼠中不存在这种舒张。缺乏PAR - 2受体在基础条件下不影响淋巴细胞黏附，但会降低淋巴细胞产生的收缩反应。去内皮损伤28天后，两种品系的血管对淋巴细胞的收缩反应均降低，而与PAR - 2基因敲除小鼠相比，PAR - 2(+/+)小鼠的淋巴细胞黏附显著增加。PAR - 2基因敲除小鼠的新生内膜面积明显减小。我们的数据表明，PAR - 2在受到刺激时调节炎症细胞黏附，在缺乏PAR - 2受体的小鼠中，对损伤血管的黏附减少，从而新生内膜形成也减少。
