PI3K和Akt在心血管疾病中的作用
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摘要
PI3K-Akt信号通路在细胞增殖和代谢中发挥了重要作用,并且PI3K-Akt信号通路在心脏保护机制——缺血预适应和缺血后适应中发挥重要作用。本文通过分析PI3K分子和Akt分子以及PI3K-Akt信号通路对心脏和血管生理性和病理性的影响,旨在了解其在心血管疾病中的作用。
The PI3K-Akt signaling pathway plays an important role in cell proliferation and metabolism, and the PI3K-Akt signaling pathway plays an important role in cardiac protective mechanisms-ischemic preconditioning and ischemic postconditioning. In this paper, the effects of PI3K molecule and Akt molecule and PI3K-Akt signaling pathway on cardiac and vascular physiology and pathology are analyzed in order to understand its role in cardiovascular diseases.
The PI3K-Akt signaling pathway plays an important role in cell proliferation and metabolism, and the PI3K-Akt signaling pathway plays an important role in cardiac protective mechanisms-ischemic preconditioning and ischemic postconditioning. In this paper, the effects of PI3K molecule and Akt molecule and PI3K-Akt signaling pathway on cardiac and vascular physiology and pathology are analyzed in order to understand its role in cardiovascular diseases.
引文
[1] 胡盛寿,高润霖,刘力生,等.《中国心血管病报告 2018》概要[J].中国循环杂志,2019,34:209-220.
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[3] Zhang Y,Lv F,Jin L,et al.MG53 participates in ischaemic postconditioning through the RISK signalling pathway[J].Cardiovasc Res,2011,91:108-115.
[4] Heusch G,Gersh BJ.The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion:a continual challenge[J].Eur Heart J,2017,38:774-784.
[5] Nakada Y,Canseco DC,Thet S,et al.Hypoxia induces heart regeneration in adult mice[J].Nature,2017,541:222-227.
[6] Zebrowski DC,Vergarajauregui S,Wu CC,et al.Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes[J].Elife,2015,4:e05563.doi:10.7554/eLife.05563.
[7] Hirose K,Payumo AY,Cutie S,et al.Evidence for hormonal control of heart regenerative capacity during endothermy acquisition[J].Science,2019,364:184-188.
[8] Bilanges B,Posor Y,Vanhaesebroeck B.PI3K isoforms in cell signalling and vesicle trafficking[J].Nat Rev Mol Cell Biol,2019.doi:10.1038/s41580-019-0129-z.
[9] Fruman DA,Chiu H,Hopkins BD,et al.The PI3K pathway in human disease[J].Cell,2017,170:605-635.
[10] Ghigo A,Laffargue M,Li M,et al.PI3K and calcium signaling in cardiovascular disease[J].Circ Res,2017,121:282-292.doi:10.1161/CIRCRESAHA.117.310183.
[11] Castel P,Carmona FJ,Grego-Bessa J,et al.Somatic PIK3CA mutations as a driver of sporadic venous malformations[J].Sci Transl Med,2016,8:332-342.
[12] Huang X,Dai Z,Cai L,et al.Endothelial p110γPI3K mediates endothelial regeneration and vascular repair After inflammatory vascular injury[J].Circulation,2016,133:1093-1103.
[13] Manning BD,Toker A.AKT/PKB signaling:navigating the network[J].Cell,2017,169:381-405.
[14] Revathidevi S,Munirajan AK.Akt in cancer:mediator and more[J].Semin Cancer Biol,2019.doi:10.1016/j.semcancer.2019.06.002.
[15] Maack C.The cardiac re-AKT-ion to chronic volume overload[J].Eur J Heart Fail,2016,18:372-374.
[16] Roy R,Krenz M.Heterozygous deletion of AKT1 rescues cardiac contractility,but not hypertrophy,in a mouse model of noonan syndrome with multiple lentigines[J].J Mol Cell Cardiol,2017,112:83-90.
[17] Xu BC,Long HB,Luo KQ.Tert-butylhydroquinone lowers blood pressure in AngII-induced hypertension in mice via proteasome-PTEN-Akt-eNOS pathway[J].Sci Rep,2016,6:29589.doi:10.1038/srep29589.
[18] Laakkonen JP,Lappalainen JP,Theelen TL,et al.Differential regulation of angiogenic cellular processes and claudin-5 by histamine and VEGF via PI3K-signaling,transcription factor SNAI2 and interleukin-8[J].Angiogenesis,2017,20:109-124.
[19] Findley CM,Mitchell RG,Duscha BD,et al.Plasma levels of soluble Tie2 and vascular endothelial growth factor distinguish critical limb ischemia from intermittent claudication in patients with peripheral arterial disease[J].J Am Coll Cardiol,2008,52:387-393.
[20] Abhinand CS,Raju R,Soumya SJ,et al.VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis[J].J Cell Commun Signal,2016,10:347-354.
[21] Lu ZY,Li RL,Zhou HS,et al.Therapeutic ultrasound reverses peripheral ischemia in type 2 diabetic mice through PI3K-Akt-eNOS pathway[J].Am J Transl Res,2016,8:3666-3677.
[22] Lee MY,Gamez-Mendez A,Zhang J,et al.Endothelial cell autonomous role of Akt1:regulation of vascular tone and ischemia-induced arteriogenesis[J].Arterioscler Thromb Vasc Biol,2018,38:870-879.
[23] Linton MF,Moslehi JJ,Babaev VR.Akt signaling in macrophage polarization,survival,and atherosclerosis[J].Int J Mol Sci,2019,20:2703.doi:10.3390/ijms20112703.
[24] Wu HK,Zhang Y,Cao CM,et al.Glucose-sensitive myokine/cardiokine MG53 regulates systemic insulin response and metabolic homeostasis[J].Circulation,2019,139:901-914.
[25] Tan P,Wang YJ,Li S,et al.The PI3K/Akt/mTOR pathway regulates the replicative senescence of human VSMCs[J].Mol Cell Biochem,2016,422:1-10.
[2] Cao CM,Zhang Y,Weisleder N,et al.MG53 constitutes a primary determinant of cardiac ischemic preconditioning[J].Circulation,2010,121:2565-2574.
[3] Zhang Y,Lv F,Jin L,et al.MG53 participates in ischaemic postconditioning through the RISK signalling pathway[J].Cardiovasc Res,2011,91:108-115.
[4] Heusch G,Gersh BJ.The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion:a continual challenge[J].Eur Heart J,2017,38:774-784.
[5] Nakada Y,Canseco DC,Thet S,et al.Hypoxia induces heart regeneration in adult mice[J].Nature,2017,541:222-227.
[6] Zebrowski DC,Vergarajauregui S,Wu CC,et al.Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes[J].Elife,2015,4:e05563.doi:10.7554/eLife.05563.
[7] Hirose K,Payumo AY,Cutie S,et al.Evidence for hormonal control of heart regenerative capacity during endothermy acquisition[J].Science,2019,364:184-188.
[8] Bilanges B,Posor Y,Vanhaesebroeck B.PI3K isoforms in cell signalling and vesicle trafficking[J].Nat Rev Mol Cell Biol,2019.doi:10.1038/s41580-019-0129-z.
[9] Fruman DA,Chiu H,Hopkins BD,et al.The PI3K pathway in human disease[J].Cell,2017,170:605-635.
[10] Ghigo A,Laffargue M,Li M,et al.PI3K and calcium signaling in cardiovascular disease[J].Circ Res,2017,121:282-292.doi:10.1161/CIRCRESAHA.117.310183.
[11] Castel P,Carmona FJ,Grego-Bessa J,et al.Somatic PIK3CA mutations as a driver of sporadic venous malformations[J].Sci Transl Med,2016,8:332-342.
[12] Huang X,Dai Z,Cai L,et al.Endothelial p110γPI3K mediates endothelial regeneration and vascular repair After inflammatory vascular injury[J].Circulation,2016,133:1093-1103.
[13] Manning BD,Toker A.AKT/PKB signaling:navigating the network[J].Cell,2017,169:381-405.
[14] Revathidevi S,Munirajan AK.Akt in cancer:mediator and more[J].Semin Cancer Biol,2019.doi:10.1016/j.semcancer.2019.06.002.
[15] Maack C.The cardiac re-AKT-ion to chronic volume overload[J].Eur J Heart Fail,2016,18:372-374.
[16] Roy R,Krenz M.Heterozygous deletion of AKT1 rescues cardiac contractility,but not hypertrophy,in a mouse model of noonan syndrome with multiple lentigines[J].J Mol Cell Cardiol,2017,112:83-90.
[17] Xu BC,Long HB,Luo KQ.Tert-butylhydroquinone lowers blood pressure in AngII-induced hypertension in mice via proteasome-PTEN-Akt-eNOS pathway[J].Sci Rep,2016,6:29589.doi:10.1038/srep29589.
[18] Laakkonen JP,Lappalainen JP,Theelen TL,et al.Differential regulation of angiogenic cellular processes and claudin-5 by histamine and VEGF via PI3K-signaling,transcription factor SNAI2 and interleukin-8[J].Angiogenesis,2017,20:109-124.
[19] Findley CM,Mitchell RG,Duscha BD,et al.Plasma levels of soluble Tie2 and vascular endothelial growth factor distinguish critical limb ischemia from intermittent claudication in patients with peripheral arterial disease[J].J Am Coll Cardiol,2008,52:387-393.
[20] Abhinand CS,Raju R,Soumya SJ,et al.VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis[J].J Cell Commun Signal,2016,10:347-354.
[21] Lu ZY,Li RL,Zhou HS,et al.Therapeutic ultrasound reverses peripheral ischemia in type 2 diabetic mice through PI3K-Akt-eNOS pathway[J].Am J Transl Res,2016,8:3666-3677.
[22] Lee MY,Gamez-Mendez A,Zhang J,et al.Endothelial cell autonomous role of Akt1:regulation of vascular tone and ischemia-induced arteriogenesis[J].Arterioscler Thromb Vasc Biol,2018,38:870-879.
[23] Linton MF,Moslehi JJ,Babaev VR.Akt signaling in macrophage polarization,survival,and atherosclerosis[J].Int J Mol Sci,2019,20:2703.doi:10.3390/ijms20112703.
[24] Wu HK,Zhang Y,Cao CM,et al.Glucose-sensitive myokine/cardiokine MG53 regulates systemic insulin response and metabolic homeostasis[J].Circulation,2019,139:901-914.
[25] Tan P,Wang YJ,Li S,et al.The PI3K/Akt/mTOR pathway regulates the replicative senescence of human VSMCs[J].Mol Cell Biochem,2016,422:1-10.
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