G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans.
G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans.
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DOI：
10.1161/hypertensionaha.108.125955
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Eckhart AD
中科院分区：
文献类型：
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作者：
Cohn HI;Xi Y;Pesant S;Harris DM;Hyslop T;Falkner B;Eckhart AD
与其他群体相比，美国黑人中高血压的患病率和发病率更高。高血压患者存在7种跨膜受体信号转导通路的改变。GRKs在调节该受体信号转导中起着重要作用。在心血管系统中表达最丰富的两个GRKs是GRK2和GRK5，每个都有独特的底物。了解表达的变化可能使我们深入了解激活的受体在高血压的病理生理过程中的作用。在心力衰竭和高加索高血压患者中，由于特定受体的神经激素刺激，GRK2表达增加。GRK2随后使包括β-肾上腺素能受体在内的特定受体脱敏。在血压控制中，β-肾上腺素能受体脱敏可导致血压升高。用实时定量聚合酶链式反应检测美国黑人淋巴细胞中GRK2和GRK5mRNA的表达。GRK2mRNA的表达与血压和去甲肾上腺素水平直接相关。在那些收缩压等于或大于130毫米汞柱的人中，GRK2升高了30%。未观察到GRK5基因表达与血压和儿茶酚胺的相关性。通过单变量和多变量分析，比较糖尿病患者的病情、年龄、性别和体重指数(BMI)与GRK2的表达。在血压较高的受试者中，GRK2蛋白表达增加2倍，GRK活性增加40%。我们的数据表明，GRK2，而不是GRK5，与美国黑人血压升高有关。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中高血压的病理生理学。
Hypertension occurs with higher prevalence and morbidity in black Americans compared to other groups. Alterations in the signal transduction pathways of seven-transmembrane spanning receptors are found in hypertensive patients. GRKs play an important role in regulating this receptor signaling. The two most abundantly expressed GRKs in the cardiovascular system are GRK2 and GRK5 and each have unique substrates. Understanding changes in expression may give us insight into activated receptors in the pathophysiological progression of hypertension. In heart failure and Caucasian hypertensives, increased GRK2 expression arises because of neurohormal stimulation of particular receptors. GRK2 subsequently desensitizes specific receptors including β-adrenergic receptors. In blood pressure control, β-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 equal to or greater than 130mmHg. No significant correlation between GRK5 mRNA expression and blood pressure or catecholamines was observed. Diabetic status, age, sex and body mass index (BMI) were also examined compared to GRK2 expression using univariate and multi-variate 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.