Targeting Mitochondria for Cardiovascular Disorders: Therapeutic Potential and Obstacles

Overview

Journal Nat Rev Cardiol

Specialty Cardiology & Vascular Diseases

Date 2018 Sep 5

PMID 30177752

Citations 105

Authors

Massimo Bonora

Mariusz R Wieckowski

David A Sinclair

Guido Kroemer

Paolo Pinton

Lorenzo Galluzzi

Affiliations

Soon will be listed here.

Abstract

A large body of evidence indicates that mitochondrial dysfunction has a major role in the pathogenesis of multiple cardiovascular disorders. Over the past 2 decades, extraordinary efforts have been focused on the development of agents that specifically target mitochondria for the treatment of cardiovascular disease. Despite such an intensive wave of investigation, no drugs specifically conceived to modulate mitochondrial functions are currently available for the clinical management of cardiovascular disease. In this Review, we discuss the therapeutic potential of targeting mitochondria in patients with cardiovascular disease, examine the obstacles that have restrained the development of mitochondria-targeting agents thus far, and identify strategies that might empower the full clinical potential of this approach.

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References

Zhou H, Swanson R, Simonis U, Ma X, Cecchini G, Gray M . Poly(ADP-ribose) polymerase-1 hyperactivation and impairment of mitochondrial respiratory chain complex I function in reperfused mouse hearts. Am J Physiol Heart Circ Physiol. 2006; 291(2):H714-23. DOI: 10.1152/ajpheart.00823.2005. View

Jiang X, Li L, Ying Z, Pan C, Huang S, Li L . A Small Molecule That Protects the Integrity of the Electron Transfer Chain Blocks the Mitochondrial Apoptotic Pathway. Mol Cell. 2016; 63(2):229-239. DOI: 10.1016/j.molcel.2016.06.016. View

Choi S, Reddy P . Current and emerging strategies for the prevention of graft-versus-host disease. Nat Rev Clin Oncol. 2014; 11(9):536-47. PMC: 4151470. DOI: 10.1038/nrclinonc.2014.102. View

Brown D, Hale S, Baines C, Del Rio C, Hamlin R, Yueyama Y . Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia. J Cardiovasc Pharmacol Ther. 2013; 19(1):121-32. PMC: 4103197. DOI: 10.1177/1074248413508003. View

Sandanger O, Ranheim T, Vinge L, Bliksoen M, Alfsnes K, Finsen A . The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia-reperfusion injury. Cardiovasc Res. 2013; 99(1):164-74. DOI: 10.1093/cvr/cvt091. View

Schmidt O, Pfanner N, Meisinger C . Mitochondrial protein import: from proteomics to functional mechanisms. Nat Rev Mol Cell Biol. 2010; 11(9):655-67. DOI: 10.1038/nrm2959. View

Rusnak F, Mertz P . Calcineurin: form and function. Physiol Rev. 2000; 80(4):1483-521. DOI: 10.1152/physrev.2000.80.4.1483. View

Piquereau J, Caffin F, Novotova M, Prola A, Garnier A, Mateo P . Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload. Cardiovasc Res. 2012; 94(3):408-17. PMC: 3863708. DOI: 10.1093/cvr/cvs117. View

Ruiz M, Labarthe F, Fortier A, Bouchard B, Legault J, Bolduc V . Circulating acylcarnitine profile in human heart failure: a surrogate of fatty acid metabolic dysregulation in mitochondria and beyond. Am J Physiol Heart Circ Physiol. 2017; 313(4):H768-H781. DOI: 10.1152/ajpheart.00820.2016. View

10.

Kanamori H, Takemura G, Goto K, Maruyama R, Ono K, Nagao K . Autophagy limits acute myocardial infarction induced by permanent coronary artery occlusion. Am J Physiol Heart Circ Physiol. 2011; 300(6):H2261-71. DOI: 10.1152/ajpheart.01056.2010. View

11.

Ong S, Subrayan S, Lim S, Yellon D, Davidson S, Hausenloy D . Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation. 2010; 121(18):2012-22. DOI: 10.1161/CIRCULATIONAHA.109.906610. View

12.

Lopez-Crisosto C, Pennanen C, Vasquez-Trincado C, Morales P, Bravo-Sagua R, Quest A . Sarcoplasmic reticulum-mitochondria communication in cardiovascular pathophysiology. Nat Rev Cardiol. 2017; 14(6):342-360. DOI: 10.1038/nrcardio.2017.23. View

13.

Hu X, Fu L, Li Y, Lin Z, Liu X, Wang J . The Cardioprotective Effect of Vitamin E (Alpha-Tocopherol) Is Strongly Related to Age and Gender in Mice. PLoS One. 2015; 10(9):e0137405. PMC: 4557942. DOI: 10.1371/journal.pone.0137405. View

14.

Weinlich R, Oberst A, Beere H, Green D . Necroptosis in development, inflammation and disease. Nat Rev Mol Cell Biol. 2016; 18(2):127-136. DOI: 10.1038/nrm.2016.149. View

15.

Singh R, Wander G, Rastogi A, Shukla P, Mittal A, Sharma J . Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction. Cardiovasc Drugs Ther. 1998; 12(4):347-53. DOI: 10.1023/a:1007764616025. View

16.

Kristen A, Ackermann K, Buss S, Lehmann L, Schnabel P, Haunstetter A . Inhibition of apoptosis by the intrinsic but not the extrinsic apoptotic pathway in myocardial ischemia-reperfusion. Cardiovasc Pathol. 2013; 22(4):280-6. DOI: 10.1016/j.carpath.2013.01.004. View

17.

Tian L, Neuber-Hess M, Mewburn J, Dasgupta A, Dunham-Snary K, Wu D . Ischemia-induced Drp1 and Fis1-mediated mitochondrial fission and right ventricular dysfunction in pulmonary hypertension. J Mol Med (Berl). 2017; 95(4):381-393. PMC: 5390778. DOI: 10.1007/s00109-017-1522-8. View

18.

Krech J, Tong G, Wowro S, Walker C, Rosenthal L, Berger F . Moderate therapeutic hypothermia induces multimodal protective effects in oxygen-glucose deprivation/reperfusion injured cardiomyocytes. Mitochondrion. 2017; 35:1-10. DOI: 10.1016/j.mito.2017.04.001. View

19.

Disatnik M, Ferreira J, Campos J, Gomes K, Dourado P, Qi X . Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction. J Am Heart Assoc. 2013; 2(5):e000461. PMC: 3835263. DOI: 10.1161/JAHA.113.000461. View

20.

Burte F, Carelli V, Chinnery P, Yu-Wai-Man P . Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat Rev Neurol. 2014; 11(1):11-24. DOI: 10.1038/nrneurol.2014.228. View