Mitochondrial function as a therapeutic target in heart failure

被引：582

作者：

Brown, David A. ^{[2
]}

Perry, Justin B. ^{[2
]}

Allen, Mitchell E. ^{[2
]}

Sabbah, Hani N. ^{[3
]}

Stauffer, Brian L. ^{[4
]}

Shaikh, Saame Raza ^{[5
]}

Cleland, John G. F. ^{[6
,7
]}

Colucci, Wilson S. ^{[8
,9
]}

Butler, Javed ^{[10
]}

Voors, Adriaan A. ^{[11
]}

Anker, Stefan D. ^{[12
]}

Pitt, Bertram ^{[13
]}

Pieske, Burkert ^{[14
,15
]}

Filippatos, Gerasimos ^{[16
]}

Greene, Stephen J. ^{[17
]}

Gheorghiade, Mihai ^{[1
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 201 East Huron,Galter 3-150, Chicago, IL 60611 USA

[2] Virginia Tech, Dept Human Nutr Foods & Exercise, 1035 Integrated Life Sci Bldg,1981 Kraft Dr, Blacksburg, VA 24060 USA

[3] Henry Ford Hosp, Dept Med, Div Cardiovasc Med, 2799 W Grand Blvd, Detroit, MI 48202 USA

[4] Univ Colorado Denver, Dept Med, Div Cardiol, 12700 East 19th Ave,B139, Aurora, CO 80045 USA

[5] East Carolina Univ, Brody Sch Med, East Carolina Diabet & Obes Inst, Dept Biochem & Mol Biol, 115 Heart Dr, Greenville, NC 27834 USA

[6] Imperial Coll, Natl Heart & Lung Inst, Natl Inst Hlth Res, Cardiovasc Biomed Res Unit,Royal Brompton Hosp, London, England

[7] Imperial Coll, Natl Heart & Lung Inst, Natl Inst Hlth Res, Cardiovasc Biomed Res Unit,Harefield Hosp, London, England

[8] Boston Univ, Sch Med, Cardiovasc Med Sect, 88 East Newton St,C-8, Boston, MA 02118 USA

[9] Boston Med Ctr, 88 East Newton St,C-8, Boston, MA 02118 USA

[10] SUNY Stony Brook, Hlth Sci Ctr, Div Cardiol, T-16 Room 080, Stony Brook, NY 11794 USA

[11] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 GZ Groningen, Netherlands

[12] Univ Med Ctr Gottingen UMG, Dept Innovat Clin Trials, Robert Koch Str, D-37075 Gottingen, Germany

[13] Univ Michigan, Sch Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA

[14] Charite, Campus Virchow Klinikum, Dept Cardiol, Augustenburger Pl 1, D-13353 Berlin, Germany

[15] German Heart Ctr Berlin, Augustenburger Pl 1, D-13353 Berlin, Germany

[16] Natl & Kopodistrian Univ Athens, Athens Univ Hosp Attikon, Sch Med, Heart Failure Unit,Dept Cardiol, Rimini 1, Athens 12462, Greece

[17] Duke Univ, Med Ctr, Div Cardiol, 2301 Erwin Rd Suite 7400, Durham, NC 27705 USA

来源：

NATURE REVIEWS CARDIOLOGY | 2017年 / 14卷 / 04期

关键词：

ACTIVATOR OMECAMTIV MECARBIL; PRESERVED EJECTION FRACTION; FATTY-ACID OXIDATION; MAGNETIC-RESONANCE-SPECTROSCOPY; RECEPTOR-STIMULATED APOPTOSIS; ENERGY PHOSPHATE METABOLITES; RAT VENTRICULAR MYOCYTES; CARDIAC MYOSIN ACTIVATOR; FAILING HUMAN MYOCARDIUM; CORONARY-ARTERY-DISEASE;

D O I：

10.1038/nrcardio.2016.203

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Heart failure is a pressing worldwide public-health problem with millions of patients having worsening heart failure. Despite all the available therapies, the condition carries a very poor prognosis. Existing therapies provide symptomatic and clinical benefit, but do not fully address molecular abnormalities that occur in cardiomyocytes. This shortcoming is particularly important given that most patients with heart failure have viable dysfunctional myocardium, in which an improvement or normalization of function might be possible. Although the pathophysiology of heart failure is complex, mitochondrial dysfunction seems to be an important target for therapy to improve cardiac function directly. Mitochondrial abnormalities include impaired mitochondrial electron transport chain activity, increased formation of reactive oxygen species, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. In this Consensus Statement, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.

引用

页码：238 / 250

页数：13

共 250 条

[61]

Cardiac Metabolism in Heart Failure Implications Beyond ATP Production [J].