Cohn Heather I, Xi Yihuan, Pesant Stephanie, Harris David M, Hyslop Terry, Falkner Bonita, Eckhart Andrea D
Center for Translational Medicine, Thomas Jefferson Hospital, Philadelphia, PA, USA.
Hypertension. 2009 Jul;54(1):71-6. doi: 10.1161/HYPERTENSIONAHA.108.125955. Epub 2009 Jun 1.
Hypertension occurs with higher prevalence and morbidity in black Americans compared with other groups. Alterations in the signal transduction pathways of 7-transmembrane spanning receptors are found in hypertensive patients. G protein-coupled receptor kinases (GRKs) play an important role in regulating this receptor signaling. The 2 most abundantly expressed GRKs in the cardiovascular system are GRK2 and GRK5, and each has unique substrates. Understanding changes in expression may give us insight into activated receptors in the pathophysiological progression of hypertension. In heart failure and white hypertensives, increased GRK2 expression arises because of neurohormonal stimulation of particular receptors. GRK2 subsequently desensitizes specific receptors, including beta-adrenergic receptors. In blood pressure control, beta-adrenergic receptor desensitization could lead to increased blood pressure. GRK2 and GRK5 mRNA were evaluated in lymphocytes of black Americans via quantitative real-time PCR. GRK2 mRNA expression directly correlated with systolic blood pressure and norepinephrine levels. GRK2 was elevated >30% among those with systolic blood pressure > or =130 mm Hg. No significant correlation between GRK5 mRNA expression and blood pressure or catecholamines was observed. Diabetic status, age, sex, and body mass index were also compared with GRK2 expression using univariate and multivariate analyses. GRK2 protein expression was elevated 2-fold in subjects with higher blood pressure, and GRK activity was increased >40%. Our data suggest that GRK2, but not GRK5, is correlated with increasing blood pressure in black Americans. Understanding the receptors stimulated by increased neurohormonal activation may give insight into the pathophysiology of hypertension in this at-risk population.
与其他群体相比，美国黑人高血压的患病率和发病率更高。高血压患者中发现了7次跨膜受体信号转导途径的改变。G蛋白偶联受体激酶（GRKs）在调节这种受体信号传导中起重要作用。心血管系统中表达最丰富的两种GRKs是GRK2和GRK5，每种都有独特的底物。了解表达变化可能有助于我们深入了解高血压病理生理进展中被激活的受体。在心力衰竭和白人高血压患者中，GRK2表达增加是由于特定受体的神经激素刺激。GRK2随后使特定受体脱敏，包括β-肾上腺素能受体。在血压控制中，β-肾上腺素能受体脱敏可能导致血压升高。通过定量实时PCR评估美国黑人淋巴细胞中的GRK2和GRK5 mRNA。GRK2 mRNA表达与收缩压和去甲肾上腺素水平直接相关。收缩压≥130 mmHg的人群中GRK2升高>30%。未观察到GRK5 mRNA表达与血压或儿茶酚胺之间的显著相关性。还使用单变量和多变量分析将糖尿病状态、年龄、性别和体重指数与GRK2表达进行了比较。血压较高的受试者中GRK2蛋白表达升高了2倍，GRK活性增加>40%。我们的数据表明，在美国黑人中，与血压升高相关的是GRK2，而非GRK5。了解神经激素激活增加所刺激的受体可能有助于深入了解这一高危人群高血压的病理生理学。
