多胺在老年心血管疾病中的保护作用
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摘要
多胺(polyamines)主要包括腐胺(putrescine)、亚精胺(spermidine)和精胺(spermine),普遍存在于细胞和生物体中。多胺在细胞生长、发育、蛋白质/核酸合成和细胞信号传导等过程中发挥重要的作用。但是在衰老过程中,人体内的多胺水平逐渐降低。研究发现,老年人心血管系统中的多胺水平明显低于年轻人,而补充外源多胺能有效增加血液多胺水平,并且可以改善年龄相关的心血管疾病(cardiovasculardiseases,CVD)。因此,本文就多胺在老年CVD中的保护作用作一综述,以期为老年CVD的预防和治疗提供参考资料。
Polyamines(putrescine, spermidine and spermine) are a group of small aliphatic polycations derived from amino acids. It is ubiquitous in cells and organisms. Polyamines play an important role in cell growth, tissue development, protein/nucleic acid synthesis, and cell signaling. However, during the process of aging, the level of polyamines in the human body gradually decreases. Recent studies have found that the level of polyamines in the cardiovascular system of the elderly is significantly lower than that of the youth,and polyamine supplementation can effectively increase blood polyamines levels and benefit age-related cardiovascular diseases(CVD). Therefore, this article reviews the protective effects of polyamines in CVD in the elderly to provide helpful guidance for the prevention and treatment of aging-related CVD.
Polyamines(putrescine, spermidine and spermine) are a group of small aliphatic polycations derived from amino acids. It is ubiquitous in cells and organisms. Polyamines play an important role in cell growth, tissue development, protein/nucleic acid synthesis, and cell signaling. However, during the process of aging, the level of polyamines in the human body gradually decreases. Recent studies have found that the level of polyamines in the cardiovascular system of the elderly is significantly lower than that of the youth,and polyamine supplementation can effectively increase blood polyamines levels and benefit age-related cardiovascular diseases(CVD). Therefore, this article reviews the protective effects of polyamines in CVD in the elderly to provide helpful guidance for the prevention and treatment of aging-related CVD.
引文
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[41]Eisenberg T,Abdellatif M,Zimmermann A,et al.Dietary spermidine for lowering high blood pressure.Autophagy,2017,13(4):767-769
[42]Bollenbach A,Bakker SJL,Tsikas D.GC-MS measurement of biological N(G)-hydroxy-L-arginine,a stepmotherly investigated endogenous nitric oxide synthase substrate and arginase inhibitor.Amino Acids,2019,doi:10.1007/s00726-018-02695-x
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[46]Zhang H,Wang J,Li L,et al.Spermine and spermidine reversed age-related cardiac deterioration in rats.Oncotarget,2017,8(39):64793-64808
[47]Wei C,Wang Y,Li M,et al.Spermine inhibits endoplasmic reticulum stress-induced apoptosis:a new strategy to prevent cardiomyocyte apoptosis.Cell Physiol Biochem,2016,38(2):531-544
[48]Seiler N,Raul F.Polyamines and apoptosis.J Cell Mol Med,2005,9(3):623-642
[49]Chirino-Galindo G,Mejia-Zepeda R,Palomar-Morales M.Change in lipoperoxidation but not in scavenging enzymes activity during polyamine embryoprotection in rat embryo cultured in hyperglycemic media.In Vitro Cell Dev Biol Anim,2012,48(9):570-576
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[51]Zandalinas SI,Mittler R.ROS-induced ROS release in plant and animal cells.Free Radic Biol Med,2018,122:21-27
[52]Harold LK,Antoney J,Ahmed FH,et al.FAD-sequestering proteins protect mycobacteria against hypoxic and oxidative stress.J Biol Chem,2019,294(8):2903-2912
[53]Ron D,Walter P.Signal integration in the endoplasmic reticulum unfolded protein response.Nat Rev Mol Cell Biol,2007,8(7):519-529
[54]Woodall BP,Gustafsson AB.Autophagy-A key pathway for cardiac health and longevity.Acta Physiol(Oxf),2018,223(4):e13074
[55]Taneike M,Yamaguchi O,Nakai A,et al.Inhibition of autophagy in the heart induces age-related cardiomyopathy.Autophagy,2010,6(5):600-606
[56]Soda K,Kano Y,Sakuragi M,et al.Long-term oral polyamine intake increases blood polyamine concentrations.JNutr Sci Vitaminol(Tokyo),2009,55(4):361-366
[2]Diaz M,Degens H,Vanhees L,et al.The effects of resveratrol on aging vessels.Exp Gerontol,2016,85:41-47
[3]Bhatnagar P,Wickramasinghe K,Williams J,et al.The epidemiology of cardiovascular disease in the UK 2014.Heart,2015,101(15):1182-1189
[4]Pegg AE.Functions of polyamines in mammals.J Biol Chem,2016,291(29):14904-14912
[5]Ou Y,Wang SJ,Li D,et al.Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses.Proc Natl Acad Sci USA,2016,113(44):E6806-E6812
[6]Enot DP,Niso-Santano M,Durand S,et al.Metabolomic analyses reveal that anti-aging metabolites are depleted by palmitate but increased by oleate in vivo.Cell Cycle,2015,14(15):2399-2407
[7]Stegehake D,Kurosinski MA,Schurmann S,et al.Polyamine-independent expression of Caenorhabditis elegans antizyme.J Biol Chem,2015,290(29):18090-18101
[8]Eisenberg T,Abdellatif M,Schroeder S,et al.Cardioprotection and lifespan extension by the natural polyamine spermidine.Nat Med,2016,22(12):1428-1438
[9]Madeo F,Eisenberg T,Pietrocola F,et al.Spermidine in health and disease.Science,2018,359(6374):eaan2788
[10]Martinez-Gonzalez MA,Ros E,Estruch R.Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts.NEngl J Med,2018,379(14):1388-1389
[11]Favero G,Franceschetti L,Buffoli B,et al.Melatonin:protection against age-related cardiac pathology.Ageing Res Rev,2017,35:336-349
[12]Horn MA,Trafford AW.Aging and the cardiac collagen matrix:novel mediators of fibrotic remodelling.J Mol Cell Cardiol,2016,93:175-185
[13]Keller KM,Howlett SE.Sex differences in the biology and pathology of the aging heart.Can J Cardiol,2016,32(9):1065-1073
[14]Strait JB,Lakatta EG.Aging-associated cardiovascular changes and their relationship to heart failure.Heart Fail Clin,2012,8(1):143-164
[15]Wang WJ,Xu ZL,Yu C,et al.Effects of aflatoxin B1 on mitochondrial respiration,ROS generation and apoptosis in broiler cardiomyocytes.Anim Sci J,2017,88(10):1561-1568
[16]Bergmann O,Bhardwaj RD,Bernard S,et al.Evidence for cardiomyocyte renewal in humans.Science,2009,324(5923):98-102
[17]Nishida K,Otsu K.Autophagy during cardiac remodeling.J Mol Cell Cardiol,2016,95:11-18
[18]North BJ,Sinclair DA.The intersection between aging and cardiovascular disease.Circ Res,2012,110(8):1097-1108
[19]LaRocca TJ,Gioscia-Ryan RA,Hearon CM Jr,et al.The autophagy enhancer spermidine reverses arterial aging.Mech Ageing Dev,2013,134(7-8):314-320
[20]Brandes RP,Fleming I,Busse R.Endothelial aging.Cardiovasc Res,2005,66(2):286-294
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[22]Bress AP,Colantonio LD,Cooper RS,et al.Potential cardiovascular disease events prevented with adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline.Circulation,2019,139(1):24-36
[23]Wo Y,Brisbois EJ,Bartlett RH,et al.Recent advances in thromboresistant and antimicrobial polymers for biomedical applications:just say yes to nitric oxide(NO).Biomater Sci,2016,4(8):1161-1183
[24]Sachdev U,Lotze MT.Perpetual change:autophagy,the endothelium,and response to vascular injury.J Leukoc Biol,2017,102(2):221-235
[25]Guo F,Li X,Peng J,et al.Autophagy regulates vascular endothelial cell eNOS and ET-1 expression induced by laminar shear stress in an ex vivo perfused system.Ann Biomed Eng,2014,42(9):1978-1988
[26]Liu K,Zhao Q,Liu P,et al.ATG3-dependent autophagy mediates mitochondrial homeostasis in pluripotency acquirement and maintenance.Autophagy,2016,12(11):2000-2008
[27]Chen JY,Ye ZX,Wang XF,et al.Nitric oxide bioavailability dysfunction involves in atherosclerosis.Biomed Pharmacother,2018,97:423-428
[28]Madeo F,Bauer MA,Carmona-Gutierrez D,et al.Spermidine:a physiological autophagy inducer acting as an anti-aging vitamin in humans?Autophagy,2019,15(1):165-168
[29]Eisenberg T,Knauer H,Schauer A,et al.Induction of autophagy by spermidine promotes longevity.Nat Cell Biol,2009,11(11):1305-1314
[30]Nambeesan S,Datsenka T,Ferruzzi MG,et al.Overexpression of yeast spermidine synthase impacts ripening,senescence and decay symptoms in tomato.Plant J,2010,63(5):836-847
[31]Pucciarelli S,Moreschini B,Micozzi D,et al.Spermidine and spermine are enriched in whole blood of nona/centenarians.Rejuvenation Res,2012,15(6):590-595
[32]Minois N.Molecular basis of the'anti-aging'effect of spermidine and other natural polyamines-a mini-review.Gerontology,2014,60(4):319-326
[33]Soda K,Kano Y,Chiba F,et al.Increased polyamine intake inhibits age-associated alteration in global DNAmethylation and 1,2-dimethylhydrazine-induced tumorigenesis.PLoS One,2013,8(5):e64357
[34]Morselli E,Marino G,Bennetzen MV,et al.Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.J Cell Biol,2011,192(4):615-629
[35]Bhukel A,Madeo F,Sigrist SJ.Spermidine boosts autophagy to protect from synapse aging.Autophagy,2017,13(2):444-445
[36]Sigrist SJ,Carmona-Gutierrez D,Gupta VK,et al.Spermidine-triggered autophagy ameliorates memory during aging.Autophagy,2014,10(1):178-179
[37]Shirakabe A,Ikeda Y,Sciarretta S,et al.Aging and autophagy in the heart.Circ Res,2016,118(10):1563-1576
[38]Vellai T,Takacs-Vellai K,Sass M,et al.The regulation of aging:does autophagy underlie longevity?Trends Cell Biol,2009,19(10):487-494
[39]Soda K.Polyamine metabolism and gene methylation in conjunction with one-carbon metabolism.Int J Mol Sci,2018,19(10):e3106
[40]Mancia G,Giannattasio C.Diagnostic and therapeutic problems of isolated systolic hypertension.J Hypertens,2015,33(1):33-43
[41]Eisenberg T,Abdellatif M,Zimmermann A,et al.Dietary spermidine for lowering high blood pressure.Autophagy,2017,13(4):767-769
[42]Bollenbach A,Bakker SJL,Tsikas D.GC-MS measurement of biological N(G)-hydroxy-L-arginine,a stepmotherly investigated endogenous nitric oxide synthase substrate and arginase inhibitor.Amino Acids,2019,doi:10.1007/s00726-018-02695-x
[43]Hou E,Sun N,Zhang F,et al.Malate and aspartate increase L-arginine and nitric oxide and attenuate hypertension.Cell Rep,2017,19(8):1631-1639
[44]Yoon S,Kim M,Min HK,et al.Inhibition of heat shock protein 70 blocks the development of cardiac hypertrophy by modulating the phosphorylation of histone deacetylase 2.Cardiovasc Res,2018,doi:10.1093/cvr/cvy317
[45]Ky B,French B,May Khan A,et al.Ventricular-arterial coupling,remodeling,and prognosis in chronic heart failure.J Am Coll Cardiol,2013,62(13):1165-1172
[46]Zhang H,Wang J,Li L,et al.Spermine and spermidine reversed age-related cardiac deterioration in rats.Oncotarget,2017,8(39):64793-64808
[47]Wei C,Wang Y,Li M,et al.Spermine inhibits endoplasmic reticulum stress-induced apoptosis:a new strategy to prevent cardiomyocyte apoptosis.Cell Physiol Biochem,2016,38(2):531-544
[48]Seiler N,Raul F.Polyamines and apoptosis.J Cell Mol Med,2005,9(3):623-642
[49]Chirino-Galindo G,Mejia-Zepeda R,Palomar-Morales M.Change in lipoperoxidation but not in scavenging enzymes activity during polyamine embryoprotection in rat embryo cultured in hyperglycemic media.In Vitro Cell Dev Biol Anim,2012,48(9):570-576
[50]Li D,Liu M,Tao TQ,et al.Panax quinquefolium saponin attenuates cardiomyocyte apoptosis and opening of the mitochondrial permeability transition pore in a rat model of ischemia/reperfusion.Cell Physiol Biochem,2014,34(4):1413-1426
[51]Zandalinas SI,Mittler R.ROS-induced ROS release in plant and animal cells.Free Radic Biol Med,2018,122:21-27
[52]Harold LK,Antoney J,Ahmed FH,et al.FAD-sequestering proteins protect mycobacteria against hypoxic and oxidative stress.J Biol Chem,2019,294(8):2903-2912
[53]Ron D,Walter P.Signal integration in the endoplasmic reticulum unfolded protein response.Nat Rev Mol Cell Biol,2007,8(7):519-529
[54]Woodall BP,Gustafsson AB.Autophagy-A key pathway for cardiac health and longevity.Acta Physiol(Oxf),2018,223(4):e13074
[55]Taneike M,Yamaguchi O,Nakai A,et al.Inhibition of autophagy in the heart induces age-related cardiomyopathy.Autophagy,2010,6(5):600-606
[56]Soda K,Kano Y,Sakuragi M,et al.Long-term oral polyamine intake increases blood polyamine concentrations.JNutr Sci Vitaminol(Tokyo),2009,55(4):361-366