Watts Stephanie W, Darios Emma S, Mullick Adam E, Garver Hannah, Saunders Thomas L, Hughes Elizabeth D, Filipiak Wanda E, Zeidler Michael G, McMullen Nichole, Sinal Christopher J, Kumar Ramya K, Ferland David J, Fink Gregory D
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA.
Ionis Pharmaceuticals, Carlsbad, California, USA.
FASEB J. 2018 Jun 15;32(12):fj201800479. doi: 10.1096/fj.201800479.
Measures of the adipokine chemerin are elevated in multiple cardiovascular diseases, including hypertension, but little mechanistic work has been done to implicate chemerin as being causative in such diseases. The chemerin knockout (KO) rat was created to test the hypothesis that removal of chemerin would reduce pressure in the normal and hypertensive state. Western analyses confirmed loss of chemerin in the plasma and tissues of the KO vs. wild-type (WT) rats. Chemerin concentration in plasma and tissues was lower in WT females than in WT males, as determined by Western analysis. Conscious male and female KO rats had modest differences in baseline measures vs. the WT that included systolic, diastolic, mean arterial and pulse pressures, and heart rate, all measured telemetrically. The mineralocorticoid deoxycorticosterone acetate (DOCA) and salt water, combined with uninephrectomy as a hypertensive stimulus, elevated mean and systolic blood pressures of the male KO higher than the male WT. By contrast, all pressures in the female KO were lower than their WT throughout DOCA-salt treatment. These results revealed an unexpected sex difference in chemerin expression and the ability of chemerin to modify blood pressure in response to a hypertensive challenge.-Watts, S. W., Darios, E. S., Mullick, A. E., Garver, H., Saunders, T. L., Hughes, E. D., Filipiak, W. E., Zeidler, M. G., McMullen, N., Sinal, C. J., Kumar, R. K., Ferland, D. J., Fink, G. D. The chemerin knockout rat reveals chemerin dependence in female, but not male, experimental hypertension.
脂肪因子chemerin的水平在包括高血压在内的多种心血管疾病中都会升高，但关于chemerin在这些疾病中致病机制的研究很少。为了验证去除chemerin是否会降低正常和高血压状态下的血压这一假设，研究人员培育了chemerin基因敲除（KO）大鼠。蛋白质免疫印迹分析证实，与野生型（WT）大鼠相比，KO大鼠血浆和组织中chemerin缺失。蛋白质免疫印迹分析表明，WT雌性大鼠血浆和组织中的chemerin浓度低于WT雄性大鼠。通过遥测法测量发现，清醒状态下的雄性和雌性KO大鼠与WT大鼠相比，在包括收缩压、舒张压、平均动脉压和脉压以及心率在内的基线测量值上存在适度差异。盐皮质激素醋酸脱氧皮质酮（DOCA）和盐水，联合单侧肾切除作为高血压刺激因素，使雄性KO大鼠的平均血压和收缩压升高幅度高于雄性WT大鼠。相比之下，在整个DOCA-盐处理过程中，雌性KO大鼠的所有血压值均低于其WT大鼠。这些结果揭示了chemerin表达以及chemerin在应对高血压挑战时调节血压能力方面出人意料的性别差异。——瓦茨，S.W.，达里奥斯，E.S.，穆利克，A.E.，加弗，H.，桑德斯，T.L.，休斯，E.D.，菲利皮亚克，W.E.，蔡德勒，M.G.，麦克马伦，N.，西纳尔，C.J.，库马尔，R.K.，费兰，D.J.，芬克，G.D.。chemerin基因敲除大鼠揭示了实验性高血压中雌性而非雄性对chemerin的依赖性。
