Cyclic Nucleotide-Directed Protein Kinases in Cardiovascular Inflammation and Growth.
Cyclic Nucleotide-Directed Protein Kinases in Cardiovascular Inflammation and Growth.
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DOI：
10.3390/jcdd5010006
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发表时间：
2018-01-23
影响因子：
2.4
通讯作者：
Tulis DA
中科院分区：
文献类型：
--
作者：
Holland NA;Francisco JT;Johnson SC;Morgan JS;Dennis TJ;Gadireddy NR;Tulis DA
心血管疾病（CVD），包括心肌梗死（MI）和外周或冠状动脉疾病（PAD、CAD），仍然是美国和世界范围内个体的头号杀手，每年造成近1800万（>30%）全球死亡。尽管大量的基础科学和临床研究旨在确定CVD的关键病因组成部分和潜在的治疗靶点，但患有这些可怕疾病的人数仍在继续上升。在迄今为止表征的具有控制CVD的基础方面的潜力的许多生物化学、分子和细胞元件和过程中，多方面的环核苷酸途径继续具有主要的基础科学和临床兴趣。环磷酸腺苷（cAMP）和环磷酸鸟苷（cGMP）及其大量下游蛋白激酶效应物不仅在心血管稳态中而且在CVD的发病机制中发挥普遍作用。环核苷酸及其下游靶标已经是CVD以及其他病理学的临床药物治疗的主要靶标，但仍在发现新的和潜在的临床吸引力作用。考虑到这一点，这篇综述文章侧重于我们目前的知识状态的环核苷酸驱动的丝氨酸（Ser）/苏氨酸（Thr）蛋白激酶在CVD特别强调环AMP依赖性蛋白激酶（PKA）和环GMP依赖性蛋白激酶（PKG）。注意这些激酶与炎性成分，包括白细胞介素6信号，与G蛋白偶联受体和生长因子信号，并与CVD发病机制的基础生长和合成转录平台的监管相互作用。本文最后简要讨论了潜在的未来发展方向，并强调了环核苷酸导向蛋白激酶作为心脏和血管疾病病理学的新兴和关键控制者的持续基础科学和临床研究的重要性。
Cardiovascular disease (CVD), including myocardial infarction (MI) and peripheral or coronary artery disease (PAD, CAD), remains the number one killer of individuals in the United States and worldwide, accounting for nearly 18 million (>30%) global deaths annually. Despite considerable basic science and clinical investigation aimed at identifying key etiologic components of and potential therapeutic targets for CVD, the number of individuals afflicted with these dreaded diseases continues to rise. Of the many biochemical, molecular, and cellular elements and processes characterized to date that have potential to control foundational facets of CVD, the multifaceted cyclic nucleotide pathways continue to be of primary basic science and clinical interest. Cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP) and their plethora of downstream protein kinase effectors serve ubiquitous roles not only in cardiovascular homeostasis but also in the pathogenesis of CVD. Already a major target for clinical pharmacotherapy for CVD as well as other pathologies, novel and potentially clinically appealing actions of cyclic nucleotides and their downstream targets are still being discovered. With this in mind, this review article focuses on our current state of knowledge of the cyclic nucleotide-driven serine (Ser)/threonine (Thr) protein kinases in CVD with particular emphasis on cyclic AMP-dependent protein kinase (PKA) and cyclic GMP-dependent protein kinase (PKG). Attention is given to the regulatory interactions of these kinases with inflammatory components including interleukin 6 signals, with G protein-coupled receptor and growth factor signals, and with growth and synthetic transcriptional platforms underlying CVD pathogenesis. This article concludes with a brief discussion of potential future directions and highlights the importance for continued basic science and clinical study of cyclic nucleotide-directed protein kinases as emerging and crucial controllers of cardiac and vascular disease pathologies.
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