Regulation of GPCR signaling in hypertension.
Regulation of GPCR signaling in hypertension.
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DOI：
10.1016/j.bbadis.2010.01.005
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发表时间：
2010-12
影响因子：
6.2
通讯作者：
Eckhart, Andrea D.
中科院分区：
文献类型：
--
作者：
Brinks, Henriette L.;Eckhart, Andrea D.
高血压是一种复杂的多因素疾病，是工业化国家发病率和死亡率的主要原因：缺血性和高血压性心脏病、中风、外周动脉粥样硬化和肾功能衰竭。目前对高血压的药物治疗主要集中在通过抑制儿茶酚胺和血管紧张素II等激素，阻断它们的受体激活来调节血管阻力。G蛋白偶联受体激酶(GRKs)和G蛋白信号转导调节蛋白(RGS)蛋白与激活的G蛋白偶联受体(GPCRs)相互作用，影响受体的磷酸化状态，导致脱敏，从而严重影响信号转导。通过这些调节剂调节GPCR的缺陷会严重影响GPCR在高血压等病理情况下刺激的生物反应，因为它们微调和平衡血管收缩和扩张的主要递质，因此为抗高血压治疗策略提供了有价值的新靶点。GRKs水平升高与人类高血压疾病有关，并在高血压动物模型中是相关的血压调节器。这意味着对一种疾病的治疗前景，这种疾病在美国的流行率为6500万，同时与主要不良心脏和血管事件的发生直接相关。因此，使用抑制GRKs来调节GPCRs的治疗方法是治疗高血压和心力衰竭的有趣的新靶点。
Hypertension represents a complex, multifactorial disease and contributes to the major causes of morbidity and mortality in industrialized countries: ischemic and hypertensive heart disease, stroke, peripheral atherosclerosis and renal failure. Current pharmacological therapy of essential hypertension focuses on the regulation of vascular resistance by inhibition of hormones such as catecholamines and angiotensin II, blocking them from receptor activation. Interaction of G-protein coupled receptor kinases (GRKs) and Regulator of G-Protein Signaling (RGS) proteins with activated G-protein coupled receptors (GPCRs) effect the phosphorylation state of the receptor leading to desensitization and can profoundly impair signalling. Defects in GPCR regulation via these modulators have severe consequences affecting GPCR-stimulated biological responses in pathological situations such as hypertension, since they fine-tune and balance the major transmitters of vessel constriction versus dilatation, thus representing valuable new targets for anti-hypertensive therapeutic strategies. Elevated levels of GRKs are associated with human hypertensive disease and are relevant modulators of blood pressure in animal models of hypertension. This implies therapeutic perspective in a disease that has a prevalence of 65 million in the United States while being directly correlated with occurrence of major adverse cardiac and vascular events. Therefore, therapeutic approaches using the inhibition of GRKs to regulate GPCRs are intriguing novel targets for treatment of hypertension and heart failure.
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影响因子：
15.9
作者：
Amberg, GC;Bonev, AD;Santana, LF
通讯作者：
Santana, LF
影响因子：
8.3
作者：
Anderson, KM;Eckhart, AD;Koch, WJ
通讯作者：
Koch, WJ
影响因子：
3.6
作者：
Eckhart, AD;Ozaki, T;Koch, WJ
通讯作者：
Koch, WJ
影响因子：
37.8
作者：
Chakir K;Daya SK;Aiba T;Tunin RS;Dimaano VL;Abraham TP;Jaques-Robinson KM;Lai EW;Pacak K;Zhu WZ;Xiao RP;Tomaselli GF;Kass DA
通讯作者：
Kass DA
DOI：
10.1161/hypertensionaha.108.125955
发表时间：
2009-07
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Cohn HI;Xi Y;Pesant S;Harris DM;Hyslop T;Falkner B;Eckhart AD
通讯作者：
Eckhart AD