Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure.
Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure.
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DOI：
10.1016/j.pharmthera.2018.09.001
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发表时间：
2019-01
影响因子：
13.5
通讯作者：
Taylor JM
中科院分区：
文献类型：
--
作者：
Dee RA;Mangum KD;Bai X;Mack CP;Taylor JM
在过去的几十年里，高血压(也称为高血压)的患病率一直在稳步上升。众所周知，高血压是一种沉默的杀手，它会增加心血管疾病的风险，并可能导致中风、心脏病发作、肾衰竭和相关的后遗症。虽然目前有许多高血压治疗方法可用，但据估计，只有一半的药物治疗患者表现出血压控制。这意味着需要更好地了解疾病的根本原因，并需要更有效的治疗方法。虽然血压动态平衡是非常复杂的，涉及到多个身体系统的综合控制，但血管收缩和动脉阻力是重要的因素。来自临床前动物模型和全基因组相关性研究的有力证据表明，平滑肌收缩和BP动态平衡是由小GTP酶RhoA及其下游靶标Rho激酶控制的。在这篇综述中，我们总结了在平滑肌细胞中对RhoA活性进行严格的时空调控的信号通路和调节因子，并讨论了目前针对这些RhoA通路成分的治疗策略。我们还讨论了RhoA途径中已知的等位基因变异，并考虑了这些多态如何影响高血压及其临床表现的遗传风险。
The prevalence of high blood pressure (also known as hypertension) has steadily increased over the last few decades. Known as a silent killer, hypertension increases the risk for cardiovascular disease and can lead to stroke, heart attack, kidney failure and associated sequela. While numerous hypertensive therapies are currently available, it is estimated that only half of medicated patients exhibit blood pressure control. This signifies the need for a better understanding of the underlying cause of disease and for more effective therapies. While blood pressure homeostasis is very complex and involves the integrated control of multiple body systems, smooth muscle contractility and arterial resistance are important contributors. Strong evidence from pre-clinical animal models and genome-wide association studies indicate that smooth muscle contraction and BP homeostasis are governed by the small GTPase RhoA and its downstream target, Rho kinase. In this review, we summarize the signaling pathways and regulators that impart tight spatial-temporal control of RhoA activity in smooth muscle cells and discuss current therapeutic strategies to target these RhoA pathway components. We also discuss known allelic variations in the RhoA pathway and consider how these polymorphisms may affect genetic risk for hypertension and its clinical manifestations.
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DOI：
10.1111/j.1749-6632.2012.06506.x
发表时间：
2012-01-01
期刊：
BARRIERS AND CHANNELS FORMED BY TIGHT JUNCTION PROTEINS I
影响因子：
--
作者：
Citi, Sandra;Pulimeno, Pamela;Paschoud, Serge
通讯作者：
Paschoud, Serge
影响因子：
4.8
作者：
Bear, Michael D.;Li, Min;Toksoz, Deniz
通讯作者：
Toksoz, Deniz
影响因子：
15.9
作者：
Bai, Xue;Mangum, Kevin D.;Mack, Christopher P.
通讯作者：
Mack, Christopher P.
影响因子：
64.8
作者：
Boyden, Lynn M.;Choi, Murim;Choate, Keith A.;Nelson-Williams, Carol J.;Farhi, Anita;Toka, Hakan R.;Tikhonova, Irina R.;Bjornson, Robert;Mane, Shrikant M.;Colussi, Giacomo;Lebel, Marcel;Gordon, Richard D.;Semmekrot, Ben A.;Poujol, Alain;Valimaki, Matti J.;De Ferrari, Maria E.;Sanjad, Sami A.;Gutkin, Michael;Karet, Fiona E.;Tucci, Joseph R.;Stockigt, Jim R.;Keppler-Noreuil, Kim M.;Porter, Craig C.;Anand, Sudhir K.;Whiteford, Margo L.;Davis, Ira D.;Dewar, Stephanie B.;Bettinelli, Alberto;Fadrowski, Jeffrey J.;Belsha, Craig W.;Hunley, Tracy E.;Nelson, Raoul D.;Trachtman, Howard;Cole, Trevor R. P.;Pinsk, Maury;Bockenhauer, Detlef;Shenoy, Mohan;Vaidyanathan, Priya;Foreman, John W.;Rasoulpour, Majid;Thameem, Farook;Al-Shahrouri, Hania Z.;Radhakrishnan, Jai;Gharavi, Ali G.;Goilav, Beatrice;Lifton, Richard P.
通讯作者：
Lifton, Richard P.
DOI：
10.1111/jch.12830
发表时间：
2016-11
期刊：
Journal of clinical hypertension (Greenwich, Conn.)
影响因子：
--
作者：
Booth JN 3rd;Muntner P;Diaz KM;Viera AJ;Bello NA;Schwartz JE;Shimbo D
通讯作者：
Shimbo D