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Myocardial Substrate Metabolic Remodeling in Heart Failure
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 5, Pages: 210-219(2020)
- 作者机构：
北京中医药大学 东直门医院 中医内科学教育部和北京市重点实验室，中西医结合气血研究实验室，北京 100700
- 作者简介：
- 基金信息：
DOI：10.13422/j.cnki.syfjx.20200108
CLC： R2-0; R22; R285.5; R284.1Received：27 June 2019，
Published Online：11 September 2019，
Published：05 March 2020
- 稿件说明：
移动端阅览
Wen-kun CHENG, Ming-jing ZHAO, Lei WANG, et al. Myocardial Substrate Metabolic Remodeling in Heart Failure[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(5): 210-219.
Wen-kun CHENG, Ming-jing ZHAO, Lei WANG, et al. Myocardial Substrate Metabolic Remodeling in Heart Failure[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(5): 210-219. DOI： 10.13422/j.cnki.syfjx.20200108.
摘要
心力衰竭后心肌底物代谢严重受损，对葡萄糖和脂肪酸等底物的选择和利用发生重构，心肌产能不足，可导致心功能障碍和进展性左心室重构。传统观念认为，心衰时心脏从脂肪酸代谢向葡萄糖代谢转化，但近年来有些研究结果与此观点相矛盾，关于心衰后心肌能量底物代谢的改变及其调控机制的研究结论尚未统一，心衰的代谢治疗发展缓慢，因此，探讨导致这些结论异质性的原因对明确心衰底物代谢模式和研发代谢靶向药物十分必要。该综述总结了正常心肌在生理条件下的代谢模式及调控机制，同时，从心衰的病因、严重程度、持续时间、研究的物种、动物模型和代谢检测方法等多个角度，重点阐述和比较了由缺血性心脏病、压力负荷、容量负荷及扩张型心肌病诱导的心衰中心脏底物代谢的异常，初步分析了不同研究中相关结论的一致性和差异性，并对代谢治疗的未来趋势展开论述，以期初步总结出心衰后葡萄糖代谢和脂肪酸代谢变化的规律及其分子机制，并为代谢靶向治疗的研究提供线索。
Abstract
Myocardial substrate metabolism is severely impaired after heart failure
and the selection and utilization of substrates
such as glucose and fatty acids
are remodeled
resulting in insufficient myocardial productivity
cardiac dysfunction and progressive left ventricular remodeling. It is believed traditionally that the heart changes from fatty acid metabolism to glucose metabolism during heart failure
which however is contradictory with some findings in recent years. No consistent conclusion can be drawn from studies on the changes of myocardial energy substrate metabolism and its regulatory mechanism after heart failure. Metabolic treatment for heart failure has developed slowly. Therefore
it is necessary to explore the reasons for heterogeneity of these conclusions for defining the metabolic patterns of heart failure substrates and developing metabolically targeted drugs. This review summarizes the metabolic patterns and regulatory mechanisms of normal myocardium under physiological conditions
focuses on the elaboration and comparison of myocardial substrates metabolic abnormalities in heart failure induced by ischemic heart disease
pressure load
volume load and dilated cardiomyopathy in such aspects as etiology
severity
duration of heart failure
species studied
animal models and metabolic detection methods
and makes a preliminary analysis on the consistency and differences of relevant conclusions in various studies
and discusses the future trend of metabolic treatment
with the aim to summarize the rules and molecular mechanism of glucose metabolism and fatty acid metabolism after heart failure and provide clues for the research of metabolic targeted therapy.
关键词
Keywords
references
E BERTERO , C MAACK . Metabolic remodelling in heart failure [J]. Nat Rev Cardiol , 2018 ， 15 ( 8 ): 457 - 470 .
A GUPTA , B HOUSTON . A comprehensive review of the bioenergetics of fatty acid and glucose metabolism in the healthy and failing heart in nondiabetic condition [J]. Heart Fail Rev , 2017 ， 22 ( 6 ): 825 - 842 .
N FILLMORE , J MORI , G D LOPASCHUK . Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy [J]. Br J Pharmacol , 2014 ， 171 ( 8 ): 2080 - 2090 .
S KAIMOTO , A HOSHINO , M ARIYOSHI , et al . Activation of PPAR- α in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure [J]. Am J Physiol Heart Circ Physiol , 2017 ， 312 ( 2 ): H305 - H313 .
S C KOLWICZ , D P OLSON , L C MARNEY , et al . Cardiac-specific deletion of acetyl CoA carboxylase 2 prevents metabolic remodeling during pressure-overload hypertrophy [J]. Circ Res , 2012 ， 111 ( 6 ): 728 - 38 .
J M BERTHIAUME , M E YOUNG , X CHEN , et al . Normalizing the metabolic phenotype after myocardial infarction: impact of subchronic high fat feeding [J]. J Mol Cell Cardiol , 2012 ， 53 ( 1 ): 125 - 33 .
S C KOLWICZ , S PUROHIT , R TIAN . Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes [J]. Circ Res , 2013 ， 113 ( 5 ): 603 - 616 .
T TUOMAINEN , P TAVI . The role of cardiac energy metabolism in cardiac hypertrophy and failure [J]. Exp Cell Res , 2017 ， 360 ( 1 ): 12 - 18 .
M A PETERZAN , C A LYGATE , S NEUBAUER , et al . Metabolic remodeling in hypertrophied and failing myocardium: a review [J]. Am J Physiol Heart Circ Physiol , 2017 ， 313 ( 3 ): H597 - H616 .
H NOORDALI , B L LOUDON , M P FRENNEAUX , et al . Cardiac metabolism-A promising therapeutic target for heart failure [J]. Pharmacol Ther , 2018 ， 182 : 95 - 114 .
W C STANLEY , F A RECCHIA , G D LOPASCHUK . Myocardial substrate metabolism in the normal and failing heart [J]. Physiol Rev , 2005 ， 85 ( 3 ): 1093 - 129 .
S NEUBAUER . The failing heart--an engine out of fuel [J]. N Engl J Med , 2007 ， 356 ( 11 ): 1140 - 1151 .
A REMONDINO , N Rosenblatt-Velin , C Montessuit , et al . Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction [J]. J Mol Cell Cardiol , 2000 ， 32 ( 11 ): 2025 - 2034 .
P A AMORIM , T D NGUYEN , Y SHINGU , et al . Myocardial infarction in rats causes partial impairment in insulin response associated with reduced fatty acid oxidation and mitochondrial gene expression [J]. J Thorac Cardiovasc Surg , 2010 ， 140 ( 5 ): 1160 - 1167 .
M P CHANDLER , J KERNER , H HUANG , et al . Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation [J]. Am J Physiol Heart Circ Physiol , 2004 ， 287 ( 4 ): H1538 - H1543 .
N ROSENBLATT-VELIN , C MONTESSUIT , I PAPAGEORGIOU , et al . Postinfarction heart failure in rats is associated with upregulation of GLUT-1 and downregulation of genes of fatty acid metabolism [J]. Cardiovasc Res , 2001 ， 52 ( 3 ): 407 - 416 .
L C HEATHER , M A COLE , C A LYGATE , et al . Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart [J]. Cardiovasc Res , 2006 ， 72 ( 3 ): 430 - 437 .
M E CHRISTE , R L RODGERS . Altered glucose and fatty acid oxidation in hearts of the spontaneously hypertensive rat [J]. J Mol Cell Cardiol , 1994 ， 26 ( 10 ): 1371 - 1375 .
M S DODD , D R BALL , M A SCHROEDER , et al . In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart [J]. Cardiovasc Res , 2012 ， 95 ( 1 ): 69 - 76 .
T KATO , S NIIZUMA , Y INUZUKA , et al . Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure [J]. Circ Heart Fail , 2010 ， 3 ( 3 ): 420 - 430 .
Y YONEKURA , A B BRILL , P SOM , et al . Regional myocardial substrate uptake in hypertensive rats: a quantitative autoradiographic measurement [J]. Science , 1985 ， 227 ( 4693 ): 1494 - 1496 .
H DEGENS , K F DE BROUWER , A J GILDE , et al . Cardiac fatty acid metabolism is preserved in the compensated hypertrophic rat heart [J]. Basic Res Cardiol , 2006 ， 101 ( 1 ): 17 - 26 .
L ZHANG , J S JASWAL , J R USSHER , et al . Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy [J]. Circ Heart Fail , 2013 ， 6 ( 5 ): 1039 - 1048 .
A AKKI , K SMITH , A M SEYMOUR . Compensated cardiac hypertrophy is characterised by a decline in palmitate oxidation [J]. Mol Cell Biochem , 2008 ， 311 ( 1-2 ): 215 - 224 .
Y KAGAYA , Y KANNO , D TAKEYAMA , et al . Effects of long-term pressure overload on regional myocardial glucose and free fatty acid uptake in rats. A quantitative autoradiographic study [J]. Circulation , 1990 ， 81 ( 4 ): 1353 - 1361 .
T DOENST , G PYTEL , A SCHREPPER , et al . Decreased rates of substrate oxidation ex vivo predict the onset of heart failure and contractile dysfunction in rats with pressure overload [J]. Cardiovasc Res , 2010 ， 86 ( 3 ): 461 - 470 .
P ZHABYEYEV , M GANDHI , J MORI , et al . Pressure-overload-induced heart failure induces a selective reduction in glucose oxidation at physiological afterload [J]. Cardiovasc Res , 2013 ， 97 ( 4 ): 676 - 685 .
J MORI , O A ALROB , C S WAGG , et al . ANG Ⅱ causes insulin resistance and induces cardiac metabolic switch and inefficiency: a critical role of PDK4 [J]. Am J Physiol Heart Circ Physiol , 2013 ， 304 ( 8 ): H1103 - H1113 .
J MORI , R BASU , B A MCLEAN , et al . Agonist-induced hypertrophy and diastolic dysfunction are associated with selective reduction in glucose oxidation: a metabolic contribution to heart failure with normal ejection fraction [J]. Circ Heart Fail , 2012 ， 5 ( 4 ): 493 - 503 .
W DHAHRI , J COUET , É ROUSSEL ， et al . Fenofibrate reduces cardiac remodeling and improves cardiac function in a rat model of severe left ventricle volume overload [J]. Life Sci , 2013 ， 92 ( 1 ): 26 - 34 .
D LACHANCE , W DHAHRI , M C DROLET , et al . Endurance training or beta-blockade can partially block the energy metabolism remodeling taking place in experimental chronic left ventricle volume overload [J]. BMC Cardiovasc Disord , 2014 ， 14 : 190 .
A A BOUCHARD-THOMASSIN , D LACHANCE , M C DROLET , et al . A high-fructose diet worsens eccentric left ventricular hypertrophy in experimental volume overload [J]. Am J Physiol Heart Circ Physiol , 2011 ， 300 ( 1 ): H125 - H134 .
E ROUSSEL , M C DROLET , E WALSH-WILKINSON , et al . Transcriptional changes associated with long-term left ventricle volume overload in rats: impact on Enzymes related to myocardial energy metabolism [J]. Biomed Res Int , 2015 ， doi: 10.1155/2015/949624 http://dx.doi.org/10.1155/2015/949624 .
T MIYAMOTO , Y TAKEISHI , S TAZAWA , et al . Fatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded hearts [J]. Eur J Clin Invest , 2004 ， 34 ( 3 ): 176 - 181 .
J BENES , L KAZDOVA , Z DRAHOTA , et al . Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats [J]. Clin Sci (Lond) , 2011 ， 121 ( 1 ): 29 - 41 .
V G DÁVILA-ROMÁN , G VEDALA , P HERRERO , et al . Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy [J]. J Am Coll Cardiol , 2002 ， 40 ( 2 ): 271 - 7 .
D NEGLIA , A DE CATERINA , P MARRACCINI , et al . Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy [J]. Am J Physiol Heart Circ Physiol , 2007 ， 293 ( 6 ): H3270 - H3278 .
K C BEDI , N W SNYDER , J BRANDIMARTO , et al . Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure [J]. Circulation , 2016 ， 133 ( 8 ): 706 - 716 .
L A NIKOLAIDIS , A STURZU , C STOLARSKI , et al . The development of myocardial insulin resistance in conscious dogs with advanced dilated cardiomyopathy [J]. Cardiovasc Res , 2004 ， 61 ( 2 ): 297 - 306 .
F A RECCHIA , P I MCCONNELL , R D BERNSTEIN , et al . Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing-induced heart failure in the conscious dog [J]. Circ Res , 1998 ， 83 ( 10 ): 969 - 979 .
B LEI , V LIONETTI , M E YOUNG , et al . Paradoxical downregulation of the glucose oxidation pathway despite enhanced flux in severe heart failure [J]. J Mol Cell Cardiol , 2004 ， 36 ( 4 ): 567 - 576 .
J C OSORIO , W C STANLEY , A LINKE , et al . Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid X receptor-alpha in pacing-induced heart failure [J]. Circulation , 2002 ， 106 ( 5 ): 606 - 612 .
F MOUQUET , D ROUSSEAU , V DOMERGUE-DUPONT , et al . Effects of trimetazidine, a partial inhibitor of fatty acid oxidation, on ventricular function and survival after myocardial infarction and reperfusion in the rat [J]. Fundam Clin Pharmacol , 2010 ， 24 ( 4 ): 469 - 476 .
E E MORGAN , M E YOUNG , T A MCELFRESH , et al . Chronic treatment with trimetazidine reduces the upregulation of atrial natriuretic peptide in heart failure [J]. Fundam Clin Pharmacol , 2006 ， 20 ( 5 ): 503 - 505 .
V H LAM , L ZHANG , A HUQI , et al . Activating PPAR α prevents post-ischemic contractile dysfunction in hypertrophied neonatal hearts [J]. Circ Res , 2015 ， 117 ( 1 ): 41 - 51 .
P LI , S LUO , C PAN , et al . Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate [J]. Mol Med Rep , 2015 ， 12 ( 6 ): 7899 - 7906 .
Y S CHOI , A B DE MATTOS , D SHAO , et al . Preservation of myocardial fatty acid oxidation prevents diastolic dysfunction in mice subjected to angiotensin Ⅱ infusion [J]. J Mol Cell Cardiol , 2016 ， 100 : 64 - 71 .
王臻 ， 李洁白 ， 董昕 ， 等 . 补阳还五汤对舒张性心衰大鼠心肌线粒体能量代谢及AMPK/PPAR α 信号通路的影响 [J]. 中国实验方剂学杂志 ， 2019 ， 25 ( 9 ): 12 - 17 .
方焕松 ， 刘友章 ， 邱俊 ， 等 . 四君子汤对慢性心衰大鼠心肌组织蛋白质组学影响的研究 [J]. 中国实验方剂学杂志 ， 2017 ， 23 ( 5 ): 152 - 156 .
X ZHENG , S WANG , X ZOU , et al . Ginsenoside Rb1 improves cardiac function and remodeling in heart failure [J]. Exp Anim , 2017 ， 66 ( 3 ): 217 - 228 .
于永慧 ， 张佩 ， 刘剑刚 ， 等 . 气血并治方有效组分干预H/R损伤心肌细胞AMPK相关糖脂代谢通路的分析 [J]. 中国实验方剂学杂志 ， 2018 ， 24 ( 6 ): 89 - 95 .
J WANG , Z LI , Y WANG , et al . Qiliqiangxin enhances cardiac glucose metabolism and improves diastolic function in spontaneously hypertensive rats [J]. Evid Based Complement Alternat Med , 2017 ， doi: 10.1155/2017/3197320 http://dx.doi.org/10.1155/2017/3197320 .
S SHEN , H JIANG , Y BEI , et al . Qiliqiangxin attenuates adverse cardiac remodeling after myocardial infarction in ovariectomized mice via activation of PPAR γ [J]. Cell Physiol Biochem , 2017 ， 42 ( 3 ): 876 - 888 .
Q ZHANG , M SHAO , X ZHANG , et al . The effect of Chinese medicine on lipid and glucose metabolism in acute myocardial infarction through PPAR γ pathway [J]. Front Pharmacol , 2018 ， 9 : 1209 .
张晓华 ， 刘淑荣 ， 钱锋 ， 等 . 强心康颗粒对慢性心衰大鼠心肌细胞病理形态学腺苷酸转位酶，PGC-1 α mRNA表达的影响 [J]. 中国实验方剂学杂志 ， 2018 ， 24 ( 9 ): 121 - 126 .
杨禹晗 ， 陈超英 ， 袁占鹏 . 玉竹提取物对心肌缺血再灌注损伤大鼠心肌细胞线粒体损伤及凋亡的保护作用 [J]. 中国实验方剂学杂志 ， 2018 ， 24 ( 16 ): 136 - 140 .
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