Fat and cardiotoxicity in hereditary pulmonary hypertension

American Journal of Respiratory and Critical Care Medicine

Volumn 189, Issue 3, 2014, Pages 247-249

  Tuder, Rubin M ^a   Robinson, Jeffrey C ^a   Graham, Brian B ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACYLCARNITINE; ADIPOSE TRIACYLGLYCEROL LIPASE; ALBUMIN; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; CARNITINE PALMITOYLTRANSFERASE I; CD36 ANTIGEN; CERAMIDE; CHYLOMICRON; FAT; FAT DROPLET; FATTY ACID; FATTY ACID TRANSPORTER; GLUCOSE; LIPOPROTEIN LIPASE; LONG CHAIN FATTY ACID COENZYME A LIGASE; LOW DENSITY LIPOPROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PROTEIN P42; PROTEIN P44; RECEPTOR FOR ACTIVATED C KINASE 1; SMAD 1 PROTEIN; SMAD 5 PROTEIN; SMAD 8 PROTEIN; SMAD PROTEIN; SYNAPTOPHYSIN; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1; TRIACYLGLYCEROL; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG;

ACTIVE TRANSPORT; AEROBIC METABOLISM; ANGIOGRAPHY; APOPTOSIS; CARDIOMYOPATHY; CARDIOTOXICITY; CATABOLISM; CELL METABOLISM; ENERGY TRANSFER; EXERCISE; FATTY ACID OXIDATION; FATTY ACID SYNTHESIS; FATTY ACID TRANSPORT; FATTY LIVER; GENE MUTATION; GENETIC DISORDER; GLUCOSE OXIDATION; GLUCOSE TRANSPORT; GLYCOLYSIS; HEART AFTERLOAD; HEART FAILURE; HEART INFARCTION; HEART LEFT VENTRICLE; HEART LEFT VENTRICLE FAILURE; HEART MUSCLE; HEART MUSCLE CELL; HEART MUSCLE FIBROSIS; HEART RIGHT VENTRICLE; HEART RIGHT VENTRICLE FAILURE; HOMEOBOX; HYPOXIA; LETHALITY; LIPID STORAGE; LIPOLYSIS; LIPOTOXICITY; LUNG ARTERY PRESSURE; LUNG CIRCULATION; METABOLIC SYNDROME X; MITOCHONDRION; MUSCLE CELL; MUSCLE CONTRACTILITY; NONHUMAN; OBESITY; ONCOGENE SRC; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; OXYGEN CONSUMPTION; OXYGEN SUPPLY; PERFUSION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PULMONARY ARTERY; PULMONARY HYPERTENSION; QUALITY OF LIFE; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; SYSTOLIC BLOOD PRESSURE; VASCULAR LESION; WILD TYPE;

ANIMALS; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; CERAMIDES; HUMANS; HYPERTENSION, PULMONARY; HYPERTROPHY, RIGHT VENTRICULAR; LIPOLYSIS; TRIGLYCERIDES;

EID: 84893607431     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201312-2240ED     Document Type: Review

References (27)

1. Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, Dupuis J, Long CS, Rubin LJ, Smart FW, et al.; National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 2006;114:1883-1891.
2. Stacher E, Graham BB, Hunt JM, Gandjeva A, Groshong SD, McLaughlin VV, Jessup M, Grizzle WE, Aldred MA, Cool CD, et al. Modern age pathology of pulmonary arterial hypertension. Am J Respir Crit Care Med 2012;186:261-272.
3. Bogaard HJ, Natarajan R, Mizuno S, Abbate A, Chang PJ, Chau VQ, Hoke NN, Kraskauskas D, Kasper M, Salloum FN, et al. Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med 2010;182:652-660.
4. Mahmud M, Champion HC. Right ventricular failure complicating heart failure: pathophysiology, significance, and management strategies. Curr Cardiol Rep 2007;9:200-208.
5. Piao L, Marsboom G, Archer SL. Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure. J Mol Med (Berl) 2010;88: 1011-1020.
6. Gomez-Arroyo J, Mizuno S, Szczepanek K, Van Tassell B, Natarajan R, dos Remedios CG, Drake JI, Farkas L, Kraskauskas D, Wijesinghe DS, et al. Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension. Circ Heart Fail 2013;6:136-144.
7. Hemnes AR, Brittain EL, Trammell AW, Fessel JP, Austin ED, Penner N, Maynard KB, Gleaves L, Talati M, Absi T, et al. Evidence for right ventricular lipotoxicity in heritable pulmonary arterial hypertension. Am J Respir Crit Care Med 2014;189:325-334.
8. Goldberg IJ, Trent CM, Schulze PC. Lipid metabolism and toxicity in the heart. Cell Metab 2012;15:805-812.
9. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA III, Loyd JE, Nichols WC, Trembath RC; International PPH Consortium. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 2000;26:81-84.
10. West J, Harral J, Lane K, Deng Y, Ickes B, Crona D, Albu S, Stewart D, Fagan K. Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions. Am J Physiol Lung Cell Mol Physiol 2008;295:L744-L755.
11. Shi Y, Katsev S, Cai C, Evans S. BMP signaling is required for heart formation in vertebrates. Dev Biol 2000;224:226-237.
12. Beppu H, Malhotra R, Beppu Y, Lepore JJ, Parmacek MS, Bloch KD. BMP type II receptor regulates positioning of outflow tract and remodeling of atrioventricular cushion during cardiogenesis. Dev Biol 2009;331:167-175.
13. Morrell NW, Yang X, Upton PD, Jourdan KB, Morgan N, Sheares KK, Trembath RC. Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins. Circulation 2001;104:790-795.
14. Glazer NL, Macy EM, Lumley T, Smith NL, Reiner AP, Psaty BM, King GL, Tracy RP, Siscovick DS. Transforming growth factor beta-1 and incidence of heart failure in older adults: the Cardiovascular Health Study. Cytokine 2012;60:341-345.
15. Zakharova L, Nural-Guvener H, Nimlos J, Popovic S, Gaballa MA. Chronic heart failure is associated with transforming growth factor beta-dependent yield and functional decline in atrial explant-derived c-Kit1 cells. J Am Heart Assoc 2013;2:e000317.
16. van der Vusse GJ, van Bilsen M, Glatz JF. Cardiac fatty acid uptake and transport in health and disease. Cardiovasc Res 2000;45: 279-293.
17. Tuder RM, Davis LA, Graham BB. Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension. Am J Respir Crit Care Med 2012;185:260-266.
18. Foster DW. The role of the carnitine system in human metabolism. Ann N Y Acad Sci 2004;1033:1-16.
19. Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, Han X, Gross RW, Kozak R, Lopaschuk GD, et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 2002;109:121-130.
20. Chiu HC, Kovacs A, Blanton RM, Han X, Courtois M, Weinheimer CJ, Yamada KA, Brunet S, Xu H, Nerbonne JM, et al. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res 2005;96:225-233.
21. Stanley CA. New genetic defects in mitochondrial fatty acid oxidation and carnitine deficiency. Adv Pediatr 1987;34:59-88.
22. Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev 2008;88:389-419.
23. Listenberger LL, Schaffer JE. Mechanisms of lipoapoptosis: implications for human heart disease. Trends Cardiovasc Med 2002; 12:134-138.
24. Petrache I, Natarajan V, Zhen L, Medler TR, Richter AT, Cho C, Hubbard WC, Berdyshev EV, Tuder RM. Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice. Nat Med 2005;11:491-498.
25. Drosatos K, Schulze PC. Cardiac lipotoxicity: molecular pathways and therapeutic implications. Curr Heart Fail Rep 2013;10: 109-121.
26. Randle PJ. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev 1998; 14:263-283.
27. Sutendra G, Bonnet S, Rochefort G, Haromy A, Folmes KD, Lopaschuk GD, Dyck JR, Michelakis ED. Fatty acid oxidation and malonyl-CoA decarboxylase in the vascular remodeling of pulmonary hypertension. Sci Transl Med 2010;2:44ra58.