Experimentally increasing titin compliance in a novel mouse model attenuates the frank-starling mechanism but has a beneficial effect on diastole

Circulation

Volumn 129, Issue 19, 2014, Pages 1924-1936

  Methawasin, Mei ^a   Hutchinson, Kirk R ^a   Lee, Eun Jeong ^a   Smith, John E ^a   Saripalli, Chandra ^a   Hidalgo, Carlos G ^a   Ottenheijm, Coen A C ^a,b   Granzier, Henk ^a  

^a UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Connectin; Diastole; Myocardial contraction; Myocytes cardiac; Physiology

Indexed keywords

CONNECTIN; RNA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; COMPLIANCE (PHYSICAL); CONTROLLED STUDY; DIASTOLE; DIASTOLIC STIFFNESS; DOPPLER ECHOCARDIOGRAPHY; EXERCISE TEST; FEMALE; GENE DELETION; GENE EXPRESSION; HEART FUNCTION; HEART LEFT VENTRICLE; HEART MUSCLE CELL; HEART MUSCLE FIBROSIS; HETEROZYGOTE; HOMOZYGOTE; MALE; MOUSE; MOUSE MODEL; NONHUMAN; PHENOTYPE; PRESSURE VOLUME CURVE; PRIORITY JOURNAL; REDUCTION; RIGIDITY; RNA RECOGNITION MOTIF; RNA SPLICING; RNA STRUCTURE; STARLING LAW; SYSTOLE; UPREGULATION;

CONNECTIN; DIASTOLE; MYOCARDIAL CONTRACTION; MYOCYTES, CARDIAC; PHYSIOLOGY;

ANIMALS; BIOMECHANICAL PHENOMENA; CONNECTIN; DIASTOLE; ECHOCARDIOGRAPHY, DOPPLER; ELASTICITY; HEART; HETEROZYGOTE; HOMOZYGOTE; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MODELS, ANIMAL; MYOCYTES, CARDIAC; VASCULAR STIFFNESS; VENTRICULAR FUNCTION, LEFT;

EID: 84901480223     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.113.005610     Document Type: Article

References (37)

1. LeWinter MM, Granzier H. Cardiac titin: a multifunctional giant. Circulation. 2010;121:2137-2145.
2. Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S. The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circ Res. 2001;89:1065-1072.
3. Guo W, Schafer S, Greaser ML, Radke MH, Liss M, Govindarajan T, Maatz H, Schulz H, Li S, Parrish AM, Dauksaite V, Vakeel P, Klaassen S, Gerull B, Thierfelder L, Regitz-Zagrosek V, Hacker TA, Saupe KW, Dec GW, Ellinor PT, MacRae CA, Spallek B, Fischer R, Perrot A, Özcelik C, Saar K, Hubner N, Gotthardt M. RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. Nat Med. 2012;18:766-773.
4. Lahmers S, Wu Y, Call DR, Labeit S, Granzier H. Developmental control of titin isoform expression and passive stiffness in fetal and neonatal myocardium. Circ Res. 2004;94:505-513.
5. Opitz CA, Leake MC, Makarenko I, Benes V, Linke WA. Developmentally regulated switching of titin size alters myofibrillar stiffness in the perinatal heart. Circ Res. 2004;94:967-975.
6. Fukuda N, Granzier HL, Ishiwata S, Kurihara S. Physiological functions of the giant elastic protein titin in mammalian striated muscle. J Physiol Sci. 2008;58:151-159.
7. LeWinter MM, Granzier HL. Titin is a major human disease gene. Circulation. 2013;127:938-944.
8. Makarenko I, Opitz CA, Leake MC, Neagoe C, Kulke M, Gwathmey JK, del Monte F, Hajjar RJ, Linke WA. Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts. Circ Res. 2004;95:708-716.
9. Nagueh SF, Shah G, Wu Y, Torre-Amione G, King NM, Lahmers S, Witt CC, Becker K, Labeit S, Granzier HL. Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy. Circulation. 2004;110:155-162.
10. Borbély A, Falcao-Pires I, van Heerebeek L, Hamdani N, Edes I, Gavina C, Leite-Moreira AF, Bronzwaer JG, Papp Z, van der Velden J, Stienen GJ, Paulus WJ. Hypophosphorylation of the Stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium. Circ Res. 2009;104:780-786.
11. van Heerebeek L, Franssen CP, Hamdani N, Verheugt FW, Somsen GA, Paulus WJ. Molecular and cellular basis for diastolic dysfunction. Curr Heart Fail Rep. 2012;9:293-302.
12. Chung CS, Hutchinson KR, Methawasin M, Saripalli C, Smith JE 3rd, Hidalgo CG, Luo X, Labeit S, Guo C, Granzier HL. Shortening of the elastic tandem immunoglobulin segment of titin leads to diastolic dysfunction. Circulation. 2013;128:19-28.
13. King NM, Methawasin M, Nedrud J, Harrell N, Chung CS, Helmes M, Granzier H. Mouse intact cardiac myocyte mechanics: cross-bridge and titin-based stress in unactivated cells. J Gen Physiol. 2011;137:81-91.
14. Lee EJ, Nedrud J, Schemmel P, Gotthardt M, Irving TC, Granzier HL. Calcium sensitivity and myofilament lattice structure in titin N2B KO mice. Arch Biochem Biophys. 2013;535:76-83.
15. Stienen GJ, Zaremba R, Elzinga G. ATP utilization for calcium uptake and force production in skinned muscle fibres of Xenopus laevis. J Physiol. 1995;482 (pt 1):109-122.
16. Granzier HL, Radke MH, Peng J, Westermann D, Nelson OL, Rost K, King NM, Yu Q, Tschöpe C, McNabb M, Larson DF, Labeit S, Gotthardt M. Truncation of titin's elastic PEVK region leads to cardiomyopathy with diastolic dysfunction. Circ Res. 2009;105:557-564.
17. Ottenheijm CA, Knottnerus AM, Buck D, Luo X, Greer K, Hoying A, Labeit S, Granzier H. Tuning passive mechanics through differential splicing of titin during skeletal muscle development. Biophys J. 2009;97:2277-2286.
18. Cheng H, Zheng M, Peter AK, Kimura K, Li X, Ouyang K, Shen T, Cui L, Frank D, Dalton ND, Gu Y, Frey N, Peterson KL, Evans SM, Knowlton KU, Sheikh F, Chen J. Selective deletion of long but not short Cypher isoforms leads to late-onset dilated cardiomyopathy. Hum Mol Genet. 2011;20:1751-1762.
19. Anderson ME, Brown JH, Bers DM. CaMKII in myocardial hypertrophy and heart failure. J Mol Cell Cardiol. 2011;51:468-473.
20. Ohno M, Cheng CP, Little WC. Mechanism of altered patterns of left ventricular filling during the development of congestive heart failure. Circulation. 1994;89:2241-2250.
21. Layland J, Kentish JC. Positive force- and [Ca2+]i-frequency relationships in rat ventricular trabeculae at physiological frequencies. Am J Physiol. 1999;276(1 pt 2):H9-H18.
22. Allen DG, Kurihara S. The effects of muscle length on intracellular calcium transients in mammalian cardiac muscle. J Physiol. 1982;327:79-94.
23. Castillo A, Nowak R, Littlefield KP, Fowler VM, Littlefield RS. A nebulin ruler does not dictate thin filament lengths. Biophys J. 2009;96:1856-1865.
24. Granzier HL, Akster HA, Ter Keurs HE. Effect of thin filament length on the force-sarcomere length relation of skeletal muscle. Am J Physiol. 1991;260(5 pt 1):C1060-C1070.
25. Li D, Morales A, Gonzalez-Quintana J, Norton N, Siegfried JD, Hofmeyer M, Hershberger RE. Identification of novel mutations in RBM20 in patients with dilated cardiomyopathy. Clin Transl Sci. 2010;3:90-97.
26. Watanabe K, Nair P, Labeit D, Kellermayer MS, Greaser M, Labeit S, Granzier H. Molecular mechanics of cardiac titin's PEVK and N2B spring elements. J Biol Chem. 2002;277:11549-11558.
27. Radke MH, Peng J, Wu Y, McNabb M, Nelson OL, Granzier H, Gotthardt M. Targeted deletion of titin N2B region leads to diastolic dysfunction and cardiac atrophy. Proc Natl Acad Sci U S A. 2007;104:3444-3449.
28. Brenner B. The cross-bridge cycle in muscle. Mechanical, biochemical, and structural studies on single skinned rabbit psoas fibers to characterize cross-bridge kinetics in muscle for correlation with the actomyosin- ATPase in solution. Basic Res Cardiol. 1986;81(suppl 1):1-15.
29. Irving T, Wu Y, Bekyarova T, Farman GP, Fukuda N, Granzier H. Thick- filament strain and interfilament spacing in passive muscle: effect of titin-based passive tension. Biophys J. 2011;100:1499-1508.
30. Cazorla O, Lacampagne A. Regional variation in myofilament length- dependent activation. Pflugers Arch. 2011;462:15-28.
31. Lujan HL, Janbaih H, Feng HZ, Jin JP, DiCarlo SE. Myocardial ischemia, reperfusion, and infarction in chronically instrumented, intact, conscious, and unrestrained mice. Am J Physiol Regul Integr Comp Physiol. 2012;302:R1384-R1400.
32. Joho S, Ishizaka S, Sievers R, Foster E, Simpson PC, Grossman W. Left ventricular pressure-volume relationship in conscious mice. Am J Physiol Heart Circ Physiol. 2007;292:H369-H377.
33. Helmes M, Trombitás K, Granzier H. Titin develops restoring force in rat cardiac myocytes. Circ Res. 1996;79:619-626.
34. Lujan HL, Janbaih H, Feng HZ, Jin JP, DiCarlo SE. Ventricular function during exercise in mice and rats. Am J Physiol Regul Integr Comp Physiol. 2012;302:R68-R74.
35. Krüger M, Kötter S, Grützner A, Lang P, Andresen C, Redfield MM, Butt E, dos Remedios CG, Linke WA. Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs. Circ Res. 2009;104:87-94.
36. Yamasaki R, Wu Y, McNabb M, Greaser M, Labeit S, Granzier H. Protein kinase A phosphorylates titin's cardiac-specific N2B domain and reduces passive tension in rat cardiac myocytes. Circ Res. 2002;90:1181-1188.
37. Redfield MM, Chen HH, Borlaug BA, Semigran MJ, Lee KL, Lewis G, LeWinter MM, Rouleau JL, Bull DA, Mann DL, Deswal A, Stevenson LW, Givertz MM, Ofili EO, O'Connor CM, Felker GM, Goldsmith SR, Bart BA, McNulty SE, Ibarra JC, Lin G, Oh JK, Patel MR, Kim RJ, Tracy RP, Velazquez EJ, Anstrom KJ, Hernandez AF, Mascette AM, Braunwald E; RELAX Trial. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA. 2013;309:1268-1277.