ventricular myosins


Summary: Isoforms of MYOSIN TYPE II, specifically found in the ventricular muscle of the HEART. Defects in the genes encoding ventricular myosins result in FAMILIAL HYPERTROPHIC CARDIOMYOPATHY.

Top Publications

  1. Kolossov E, Lu Z, Drobinskaya I, Gassanov N, Duan Y, Sauer H, et al. Identification and characterization of embryonic stem cell-derived pacemaker and atrial cardiomyocytes. FASEB J. 2005;19:577-9 pubmed
    ..Thus, quantitation of the alpha-myosin heavy chain driven reporter gene expression allows identification and functional characterization of early cardiac subtypes. ..
  2. Ford S, Chandra M. Length-dependent effects on cardiac contractile dynamics are different in cardiac muscle containing ?- or ?-myosin heavy chain. Arch Biochem Biophys. 2013;535:3-13 pubmed publisher
    ..These data suggest a mechanism whereby greater cooperative/allosteric effects impart an enhanced length-sensitivity of XB cycling kinetics in fibers containing the slower cycling ?-MHC...
  3. Malmqvist U, Aronshtam A, Lowey S. Cardiac myosin isoforms from different species have unique enzymatic and mechanical properties. Biochemistry. 2004;43:15058-65 pubmed
    ..Thus, nature has adapted the function of cardiac myosin isoforms to optimize power output for hearts of a given species. ..
  4. Helmke S, Yen C, Cios K, Nunley K, Bristow M, Duncan M, et al. Simultaneous quantification of human cardiac alpha- and beta-myosin heavy chain proteins by MALDI-TOF mass spectrometry. Anal Chem. 2004;76:1683-9 pubmed
    ..This method is of general applicability, especially when isoform quantification is required. ..
  5. Herron T, Vandenboom R, Fomicheva E, Mundada L, Edwards T, Metzger J. Calcium-independent negative inotropy by beta-myosin heavy chain gene transfer in cardiac myocytes. Circ Res. 2007;100:1182-90 pubmed
    ..We conclude that beta-MyHC is a negative inotrope among the cardiac myofilament proteins. ..
  6. Lowey S, Lesko L, Rovner A, Hodges A, White S, Low R, et al. Functional effects of the hypertrophic cardiomyopathy R403Q mutation are different in an alpha- or beta-myosin heavy chain backbone. J Biol Chem. 2008;283:20579-89 pubmed publisher
    ..Thus, the functional consequences of the mutation are fundamentally changed depending upon the context of the cardiac MHC isoform. ..
  7. Rundell V, Geenen D, Buttrick P, de Tombe P. Depressed cardiac tension cost in experimental diabetes is due to altered myosin heavy chain isoform expression. Am J Physiol Heart Circ Physiol. 2004;287:H408-13 pubmed
    ..Given this, the depression of tension cost in this rodent model of diabetes could be fully explained by the altered myosin isoform distribution. ..
  8. Alpert N, Brosseau C, Federico A, Krenz M, Robbins J, Warshaw D. Molecular mechanics of mouse cardiac myosin isoforms. Am J Physiol Heart Circ Physiol. 2002;283:H1446-54 pubmed
    ..These residues are localized to both the motor domain and the rod. These differences in sequence and mechanical performance may be an evolutionary attempt to match a myosin's mechanical behavior to the heart's power requirements. ..
  9. Noguchi T, Camp P, Alix S, Gorga J, Begin K, Leavitt B, et al. Myosin from failing and non-failing human ventricles exhibit similar contractile properties. J Mol Cell Cardiol. 2003;35:91-7 pubmed
    ..These data suggest that the myosin isoform shift reported in human myocardial failure does not significantly contribute to the contractile deficit of this disease. ..

More Information


  1. McCloskey D, Turnbull L, Swigart P, Zambon A, Turcato S, Joho S, et al. Cardiac transgenesis with the tetracycline transactivator changes myocardial function and gene expression. Physiol Genomics. 2005;22:118-26 pubmed
    ..Furthermore, the results raise the possibility that the phenotype conferred by a target gene may be influenced by the modified genetic background of alphaMHC-tTA myocardium. ..
  2. Danzi S, Klein I. Thyroid hormone and the cardiovascular system. Minerva Endocrinol. 2004;29:139-50 pubmed
    ..Changes in serum T(3) levels in patients with chronic congestive heart failure are caused by alterations in thyroid hormone metabolism suggesting that patients may benefit from T(3) replacement in this setting. ..
  3. Sachinidis A, Gissel C, Nierhoff D, Hippler Altenburg R, Sauer H, Wartenberg M, et al. Identification of plateled-derived growth factor-BB as cardiogenesis-inducing factor in mouse embryonic stem cells under serum-free conditions. Cell Physiol Biochem. 2003;13:423-9 pubmed
    ..Similar results were obtained after stimulation of EBs with 5 microg/ml SPP. We established a serum-free protocol and identify PDGF-BB and SPP as potent factors promoting cardiogenesis in ES cells. ..
  4. Gaur M, Ritner C, Sievers R, Pedersen A, Prasad M, Bernstein H, et al. Timed inhibition of p38MAPK directs accelerated differentiation of human embryonic stem cells into cardiomyocytes. Cytotherapy. 2010;12:807-17 pubmed publisher
    ..The use of this inhibitor should improve our ability to generate hESC-derived hCM for cell-based therapy. ..
  5. Herron T, Devaney E, Mundada L, Arden E, Day S, Guerrero Serna G, et al. Ca2+-independent positive molecular inotropy for failing rabbit and human cardiac muscle by alpha-myosin motor gene transfer. FASEB J. 2010;24:415-24 pubmed publisher
    ..Our data provide evidence for a novel form of calcium-independent positive inotropy in failing cardiac myocytes by fast alpha-myosin motor protein gene transfer. ..
  6. Lowes B, Gilbert E, Abraham W, Minobe W, Larrabee P, Ferguson D, et al. Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents. N Engl J Med. 2002;346:1357-65 pubmed
    ..In idiopathic dilated cardiomyopathy, functional improvement related to treatment with beta-blockers is associated with changes in myocardial gene expression. ..
  7. Chandra M, Tschirgi M, Ford S, Slinker B, Campbell K. Interaction between myosin heavy chain and troponin isoforms modulate cardiac myofiber contractile dynamics. Am J Physiol Regul Integr Comp Physiol. 2007;293:R1595-607 pubmed
    ..At the myofilament level, coordinated expression of complementary regulatory contractile proteins produces a functional dynamic phenotype that allows the cardiovascular systems to function effectively at different heart rates. ..
  8. Rundell V, Manaves V, Martin A, de Tombe P. Impact of beta-myosin heavy chain isoform expression on cross-bridge cycling kinetics. Am J Physiol Heart Circ Physiol. 2005;288:H896-903 pubmed
    ..05 (ANOVA)] Thus cross-bridge cycling, under high strain, for alpha-MHC is three times higher than for beta-MHC. Furthermore, under isometric conditions, alpha-MHC and beta-MHC cross bridges hydrolyze ATP independently of one another. ..
  9. Danzi S, Klein S, Klein I. Differential regulation of the myosin heavy chain genes alpha and beta in rat atria and ventricles: role of antisense RNA. Thyroid. 2008;18:761-8 pubmed publisher
    ..This confirms a close positive relationship between T3 and beta-MHC AS RNA in both the atria and ventricles, while demonstrating for the first time that alpha- and beta-MHC expression is not coupled in the atria. ..
  10. Turnbull L, Zhou H, Swigart P, Turcato S, Karliner J, Conklin B, et al. Sustained preconditioning induced by cardiac transgenesis with the tetracycline transactivator. Am J Physiol Heart Circ Physiol. 2006;290:H1103-9 pubmed
    ..Furthermore, investigations of cardioprotection using the Tet system may be aberrantly influenced by sustained preconditioning induced by cardiac transgenesis with tTA. ..
  11. Palmer B, Fishbaugher D, Schmitt J, Wang Y, Alpert N, Seidman C, et al. Differential cross-bridge kinetics of FHC myosin mutations R403Q and R453C in heterozygous mouse myocardium. Am J Physiol Heart Circ Physiol. 2004;287:H91-9 pubmed
  12. Li B, Dedman J, Kaetzel M. Nuclear Ca2+/calmodulin-dependent protein kinase II in the murine heart. Biochim Biophys Acta. 2006;1763:1275-81 pubmed
    ..Our results suggest that absence of adequate Ca2+signaling through nuclear CaMKII regulated pathways leads to development of cardiac disease. ..
  13. Di Domenico M, Casadonte R, Ricci P, Santini M, Frati G, Rizzo A, et al. Cardiac and skeletal muscle expression of mutant ?-myosin heavy chains, degree of functional impairment and phenotypic heterogeneity in hypertrophic cardiomyopathy. J Cell Physiol. 2012;227:3471-6 pubmed publisher
  14. McKee L, Chen H, Regan J, Behunin S, Walker J, Walker J, et al. Sexually dimorphic myofilament function and cardiac troponin I phosphospecies distribution in hypertrophic cardiomyopathy mice. Arch Biochem Biophys. 2013;535:39-48 pubmed publisher
    ..In conclusion, female and male HCM mice display sex dimorphic myofilament function that is accompanied by a sex- and HCM-dependent distribution of sarcomeric proteins and cTnI phosphospecies. ..
  15. Hengstenberg C, Erdmann J, Charron P. Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac beta-myosin gene mutations: prediction of clinical status--is molecular genetics a new tool for the management of hypertrophic cardiomyopathy in . Cardiovasc Res. 2003;57:298-301 pubmed
  16. Wang J, Li A, Wang Z, Feng X, Olson E, Schwartz R. Myocardin sumoylation transactivates cardiogenic genes in pluripotent 10T1/2 fibroblasts. Mol Cell Biol. 2007;27:622-32 pubmed
    ..Thus, SUMO modification acted as a molecular switch to promote myocardin's role in cardiogenic gene expression. ..
  17. England J, Pang K, Parnall M, Haig M, Loughna S. Cardiac troponin T is necessary for normal development in the embryonic chick heart. J Anat. 2016;229:436-49 pubmed publisher
    ..From these studies, we suggest TNNT2 is a gene worthy of screening for those with a congenital heart defect, particularly atrial septal defects and ventricular diverticula. ..
  18. Wirth M, Wahle P. Biolistic transfection of organotypic cultures of rat visual cortex using a handheld device. J Neurosci Methods. 2003;125:45-54 pubmed
    ..We achieve a high degree of co-expression of independent plasmids coated on the same particles. The expression of the neurotrophin plasmids is demonstrated on mRNA and protein level. ..
  19. Thompson R, Buvoli M, Buvoli A, Leinwand L. Myosin filament assembly requires a cluster of four positive residues located in the rod domain. FEBS Lett. 2012;586:3008-12 pubmed publisher
    ..Our findings show that a novel assembly element with a distinct charge profile is present at the C-terminus of sarcomeric myosins. ..
  20. Ojamaa K, Kenessey A, Shenoy R, Klein I. Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat. Am J Physiol Endocrinol Metab. 2000;279:E1319-24 pubmed
  21. Hoh J, Kang L, Sieber L, Lim J, Zhong W. Myosin isoforms and fibre types in jaw-closing muscles of Australian marsupials. J Comp Physiol B. 2006;176:685-95 pubmed
  22. Kang J, Lee D, Paeng J, Lee J, Kim Y, Lee Y, et al. Development of a sodium/iodide symporter (NIS)-transgenic mouse for imaging of cardiomyocyte-specific reporter gene expression. J Nucl Med. 2005;46:479-83 pubmed
    ..The transgenic mouse can be used as an imaging model for cardiomyocyte-specific reporter gene expression and cellular differentiation into cardiomyocytes after cardiac stem or progenitor cell transplantation. ..
  23. Elsherif L, Wang X, Grachoff M, Wolska B, Geenen D, O Bryan J. Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury. PLoS ONE. 2012;7:e30129 pubmed publisher
    ..Thus, further study of the ?-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury. ..
  24. Kang S, Chemaly E, Hajjar R, Lebeche D. Resistin promotes cardiac hypertrophy via the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathways. J Biol Chem. 2011;286:18465-73 pubmed publisher
    ..These data demonstrate that resistin induces cardiac hypertrophy and myocardial insulin resistance, possibly via the AMPK/mTOR/p70(S6K) and apoptosis signal-regulating kinase 1/JNK/IRS1 pathways. ..
  25. Spitkovsky D, Sasse P, Kolossov E, Böttinger C, Fleischmann B, Hescheler J, et al. Activity of complex III of the mitochondrial electron transport chain is essential for early heart muscle cell differentiation. FASEB J. 2004;18:1300-2 pubmed
    ..We postulate that mitochondrial complex III activity is necessary for these Ca++ oscillations, which in turn are a prerequisite for cardiomyocyte differentiation. ..
  26. Velculescu V, Kinzler K. Gene expression analysis goes digital. Nat Biotechnol. 2007;25:878-80 pubmed
  27. Tirone A, Arteaga E, Pereira A, Krieger J, Buck P, Ianni B, et al. [Research of markers for the genes of the heavy chain of cardiac beta-myosin and myosin binding protein C in relatives of patients with hypertrophic cardiomyopathy]. Arq Bras Cardiol. 2005;84:467-72 pubmed
    ..In our environment, other genes, different from those described in the literature, may prevail, or there are other genetic differences related to the origin of our population and/or environmental factors. ..
  28. Edwards J. Cardiac MHC gene expression: more complexity and a step forward. Am J Physiol Heart Circ Physiol. 2008;294:H14-5 pubmed
  29. Garriock R, Meadows S, Krieg P. Developmental expression and comparative genomic analysis of Xenopus cardiac myosin heavy chain genes. Dev Dyn. 2005;233:1287-93 pubmed
    ..Comparative genomic analysis has allowed the detection of a mammalian MHC gene (MyH15) that appears to be the orthologue of vMHC, but evidence suggests that this gene is no longer active. ..
  30. Desai M, Jackson V, Zhai W, Suman S, Nair M, Beach C, et al. Proteome basis of pale, soft, and exudative-like (PSE-like) broiler breast (Pectoralis major) meat. Poult Sci. 2016;95:2696-2706 pubmed
    ..05) in normal meat. Thus, results indicated that differences in proteome abundance could be related to the meat quality differences between normal and PSE-like broiler breast meat. ..
  31. Carotenuto F, Costa A, Albertini M, Rocchi M, Rudov A, Coletti D, et al. Dietary Flaxseed Mitigates Impaired Skeletal Muscle Regeneration: in Vivo, in Vitro and in Silico Studies. Int J Med Sci. 2016;13:206-19 pubmed publisher
    ..Thus, dietary flaxseed and ALA may serve as a useful strategy for treating patients with muscle dystrophies. ..
  32. Allegra S, Bouazza L, Benetollo C, Li J, Langlois D. A 7.1 kbp beta-myosin heavy chain promoter, efficient for green fluorescent protein expression, probably induces lethality when overexpressing a mutated transforming growth factor-beta type II receptor in transgenic mice. Transgenic Res. 2005;14:69-80 pubmed
    ..Analysis of the consequences of the blocking of the TGFbeta signalling pathway in the heart will require the use of tissue specific means of conditional gene invalidation. ..
  33. Song X, Jia L, Cui W, Zhang M, Chen W, Yuan Z, et al. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats. Toxicol Appl Pharmacol. 2014;281:101-8 pubmed publisher
  34. Lowey S, Bretton V, Gulick J, Robbins J, Trybus K. Transgenic mouse ?- and ?-cardiac myosins containing the R403Q mutation show isoform-dependent transient kinetic differences. J Biol Chem. 2013;288:14780-7 pubmed publisher
    ..These transient kinetic studies on mouse cardiac myosins provide strong evidence that the functional impact of an FHC mutation on myosin depends on the isoform backbone. ..
  35. Hinton R, Michelfelder E, Marino B, Bove K, Ware S. A fetus with hypertrophic cardiomyopathy, restrictive, and single-ventricle physiology, and a beta-myosin heavy chain mutation. J Pediatr. 2010;157:164-6 pubmed publisher
    ..We describe a patient with a pathogenic familial beta-myosin heavy chain mutation who was prenatally diagnosed with left ventricular hypoplasia and restrictive diastolic physiology. ..
  36. Peterson J, Nassar R, Anderson P, Alpert N. Altered cross-bridge characteristics following haemodynamic overload in rabbit hearts expressing V3 myosin. J Physiol. 2001;536:569-82 pubmed
    ..Our findings support the likelihood that differences among other thick and thin filament proteins underlie these XBr alterations. ..
  37. Lv H, Havari E, Pinto S, Gottumukkala R, Cornivelli L, Raddassi K, et al. Impaired thymic tolerance to ?-myosin directs autoimmunity to the heart in mice and humans. J Clin Invest. 2011;121:1561-73 pubmed publisher
    ..These results thus support a role for T cell-specific therapies for myocarditis. ..
  38. Deacon J, Bloemink M, Rezavandi H, Geeves M, Leinwand L. Identification of functional differences between recombinant human ? and ? cardiac myosin motors. Cell Mol Life Sci. 2012;69:2261-77 pubmed publisher
    ..Overall, the cycle times are ten-fold faster for ?-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. Sequence analysis points to regions that might underlie the basis for this finding. ..
  39. Haddad F, Qin A, Bodell P, Jiang W, Giger J, Baldwin K. Intergenic transcription and developmental regulation of cardiac myosin heavy chain genes. Am J Physiol Heart Circ Physiol. 2008;294:H29-40 pubmed
    ..This novel observation provides more complexity to the cooperative regulation of the two genes, suggesting the involvement of epigenetic processes in the regulation of cardiac MHC gene locus. ..
  40. Konno T, Ino H, Fujino N, Hayashi K, Yamagishi M. [Restrictive cardiomyopathy associated with heart failure]. Nihon Rinsho. 2007;65 Suppl 5:430-7 pubmed
  41. Bo J, Yu W, Zhang Y, DeMayo F, Wei L. Cardiac-specific and ligand-inducible target gene expression in transgenic mice. J Mol Cell Cardiol. 2005;38:685-91 pubmed
    ..The level of the transgene returned to the basal level within 7 days after withdrawal of RU486. This system can be used to control cardiac-specific expression of transgene in a time- and dose-dependent manner. ..
  42. Knelangen J, Kurz R, Schagdarsurengin U, Fischer B, Navarrete Santos A. Short-time glucose exposure of embryonic carcinoma cells impairs their function as terminally differentiated cardiomyocytes. Biochem Biophys Res Commun. 2012;420:230-5 pubmed publisher
    ..Our data indicate that a short time glucose stress during embryonic cell determination leads to lasting effects in terminally differentiated cell function. ..
  43. Ai J, Zhang R, Gao X, Niu H, Wang N, Xu Y, et al. Overexpression of microRNA-1 impairs cardiac contractile function by damaging sarcomere assembly. Cardiovasc Res. 2012;95:385-93 pubmed publisher
    ..Our study provides the first evidence that miRNAs cause adverse structural remodelling of the heart. ..
  44. Semsarian C, Ahmad I, Giewat M, Georgakopoulos D, Schmitt J, McConnell B, et al. The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. J Clin Invest. 2002;109:1013-20 pubmed
  45. Borejdo J, Szczesna Cordary D, Muthu P, Calander N. Familial hypertrophic cardiomyopathy can be characterized by a specific pattern of orientation fluctuations of actin molecules . Biochemistry. 2010;49:5269-77 pubmed publisher
  46. Poutanen T, Tikanoja T, Jääskeläinen P, Jokinen E, Silvast A, Laakso M, et al. Diastolic dysfunction without left ventricular hypertrophy is an early finding in children with hypertrophic cardiomyopathy-causing mutations in the beta-myosin heavy chain, alpha-tropomyosin, and myosin-binding protein C genes. Am Heart J. 2006;151:725.e1-725.e9 pubmed
    ..In children with HCM-causing mutations, signs of diastolic dysfunction are found in about half of the cases, as LVH is present only in small percentage of these children. ..
  47. Tatsuguchi M, Hiratsuka E, Machida S, Nishikawa T, Imamura S, Shimizu S, et al. Swimming exercise in infancy has beneficial effect on the hearts in cardiomyopathic Syrian hamsters. J Muscle Res Cell Motil. 2004;25:69-76 pubmed
    ..6. ..
  48. Rupp H, Wahl R, Maisch B, Hansen M. Characterization of sucrose-induced changes in cardiac phenotype. Pflugers Arch. 2002;445:32-9 pubmed
    ..The data show that adrenergic activity and metabolic signals are important for an increase in myosin V1 in sucrose-fed rats, which can be associated with an unaltered SR Ca(2+) uptake rate. ..
  49. Vracar Grabar M, Russell B. Creatine kinase is an alpha myosin heavy chain 3'UTR mRNA binding protein. J Muscle Res Cell Motil. 2004;25:397-404 pubmed
  50. Charron P, Heron D, Gargiulo M, Feingold J, Oury J, Richard P, et al. Prenatal molecular diagnosis in hypertrophic cardiomyopathy: report of the first case. Prenat Diagn. 2004;24:701-3 pubmed
    ..To the best of our knowledge, this is the first report of a prenatal molecular diagnosis performed in the context of HCM. ..
  51. Chow M, Shaffer J, Harris S, Dawson J. Altered interactions between cardiac myosin binding protein-C and ?-cardiac actin variants associated with cardiomyopathies. Arch Biochem Biophys. 2014;550-551:28-32 pubmed publisher
    ..These results also provide clues regarding the binding site of the C0C2 fragment of cMyBP-C on F-actin. ..
  52. Spudich J, Aksel T, Bartholomew S, Nag S, Kawana M, Yu E, et al. Effects of hypertrophic and dilated cardiomyopathy mutations on power output by human β-cardiac myosin. J Exp Biol. 2016;219:161-7 pubmed publisher
  53. Lyn D, Liu X, Bennett N, Emmett N. Gene expression profile in mouse myocardium after ischemia. Physiol Genomics. 2000;2:93-100 pubmed
    ..Altogether, these findings indicate that expression of genes associated with a fetal transcription program may be involved with the post ischemic remodeling process in heart ventricles...