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Adaptive and Maladaptive Cardiac Hypertrophy: What Is the Effective Role of Heat Shock Transcription Factor 1?

2007; Lippincott Williams & Wilkins; Volume: 100; Issue: 3 Linguagem: Inglês

10.1161/01.res.0000259102.33446.65

1524-4571

Piercarlo Ballo, Arianna Bocelli, Sergio Mondillo,

Cardiomyopathy and Myosin Studies

HomeCirculation ResearchVol. 100, No. 3Adaptive and Maladaptive Cardiac Hypertrophy: What Is the Effective Role of Heat Shock Transcription Factor 1? Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBAdaptive and Maladaptive Cardiac Hypertrophy: What Is the Effective Role of Heat Shock Transcription Factor 1? Piercarlo Ballo, Arianna Bocelli and Sergio Mondillo Piercarlo BalloPiercarlo Ballo Cardiology Operative Unit, S. Andrea Hospital, La Spezia;, Meyer Hospital, University of Florence;, Department of Cardiovascular Diseases, University of Siena, Italy , Arianna BocelliArianna Bocelli Cardiology Operative Unit, S. Andrea Hospital, La Spezia;, Meyer Hospital, University of Florence;, Department of Cardiovascular Diseases, University of Siena, Italy and Sergio MondilloSergio Mondillo Cardiology Operative Unit, S. Andrea Hospital, La Spezia;, Meyer Hospital, University of Florence;, Department of Cardiovascular Diseases, University of Siena, Italy Originally published16 Feb 2007https://doi.org/10.1161/01.RES.0000259102.33446.65Circulation Research. 2007;100:e45–e46To the Editor:In the recent interesting article by Sakamoto et al,1 the authors found that rats undergoing exercise training showed lower degree of left ventricular (LV) hypertrophy, higher expression and activity of heat shock transcription factor 1 (HSF1), and preserved LV systolic function in comparison with rats exposed to sustained pressure overload by surgical constriction of the transverse aorta (TAC). They also observed that transgenic mice expressing constitutively active HSF1 showed less evident hypertrophic response and better systolic function than their wild-type littermates 5 weeks after TAC. Conversely, HSF1-deficient mice showed similar degree of LV hypertrophy but worse systolic function in comparison with their wild-type littermates after 4 weeks of exercise or 1 week after TAC. These data support the intriguing hypothesis that HSF1 upregulation in cardiac myocytes may play a key role in preventing LV systolic impairment in the exercise-induced hypertrophy model, and in determining the adaptive or maladaptive nature of the hypertrophic response.An important issue in the interpretation of these findings derives from the method used for the assessment of LV systolic performance. The use of unadjusted echocardiographic indices measured at the level of endocardium, such as the M-mode-derived fractional shortening used by the authors, overestimates the real performance of circumferentially oriented LV fibers, that are mostly distributed within the midwall layers.2,3 Determination of fractional shortening at the midwall is a more reliable method to explore effective LV systolic function, particularly in the presence of LV hypertrophy or altered LV geometry, and its feasibility in mice has been previously validated.4,5 Also, because of the negative effect of LV afterload on systolic shortening and ejection,6 particularly relevant when pharmacological or surgical manipulation of hemodynamic status is performed, eg, by TAC, adjustment to end-systolic LV wall stress is required to provide a load-independent index of LV systolic performance.7 This point may represent a major drawback for the main message of the study. For instance, the authors reported lower fractional shortening in pressure-overloaded (41.20±2.33%) than exercised rats (53.42±0.94%), but it should be considered that blood pressure, a major determinant of LV afterload, was considerably higher in the former (144.6±9.0 mm Hg) than in the latter group (84.4±4.3 mm Hg). Similar considerations can be made for the differences in fractional shortening observed between transgenic and wild-type mice, even considering that blood pressure was not significantly different in the 2 groups, and between HSF1-deficient and wild-type mice, as in both comparisons the potential discrepancies in LV afterload related to different end-systolic LV diameter and wall thicknesses have not been taken into account. Adjustment to wall stress is therefore necessary to exclude that any observed reduction in LV shortening might be a pure reflection of increased afterload.8 Moreover, heart rate may act as an additional confounding factor, particularly when relatively fast frequencies are analyzed.6 To date, stress- and rate-adjusted extent or velocity of midwall shortening is often used in clinical research as an echocardiographic measure of effective circumferential LV myocardial contractility.9 In this view, a study aimed at exploring the role of HSF1 in modulating LV myocardial contractility, rather than LV fractional shortening, in exercise-induced and pressure overload hypertrophy could provide new insights into the mechanisms of cardiac adaptation to different types of overload. Considering the potential importance of HSF1 in cardiac stress response,10 even in the chronic stage of myocardial hypertrophy, such analysis might also help clarifying our previous finding that increasing levels of LV afterload in a population of hypertensive humans with LV hypertrophy were associated with more evident reduction in LV myocardial contractility than in highly trained subjects with physiologic LV hypertrophy.11Additionally, it should be taken into account that circumferential systolic indices do not provide a complete description of LV systolic dynamics. Tissue Doppler imaging and strain analysis of long-axis myocardial velocities have recently gained ground as reliable methods to assess longitudinal LV systolic function,12 and their feasibility in mice has been recently demonstrated.13,14 An impairment in longitudinal LV systolic function is often found despite normality of circumferential performance,15 and has been shown to allow early detection of contractile dysfunction and prediction of mortality in mice exposed to drug-induced cardiac injury better than circumferential indices.16 Furthermore, recent evidences obtained by cardiac MRI in humans suggest that longitudinal left atrioventricular plane excursion is the most important determinant of LV pump function, as it accounts for approximately 60% of the total LV stroke volume.17 Based on these considerations, the nice study by Sakamoto et al suggests a potential involvement of HSF1 in determining the different hypertrophic response to exercise and chronic pressure overload, but further studies are needed to investigate its effective role in affecting LV systolic function and in characterizing the adaptive or maladaptive nature of LV hypertrophy in these conditions.1 Sakamoto M, Minamino T, Toko H, Kayama Y, Zou Y, Sano M, Takaki E, Aoyagi T, Tojo K, Tajima N, Nakai A, Aburatani H, Komuro I. Upregulation of heat shock transcription factor 1 plays a critical role in adaptive cardiac hypertrophy. Circ Res. 2006; 99: 1411–1418.LinkGoogle Scholar2 De Simone G, Devereux RB, Volpe M, Camargo MJ, Wallerson DC, Laragh JH Midwall LV mechanics in rats with or without renovascular hypertension: effect of different Na+ intakes. Am J Physiol. 1996; 270: H628–H637.CrossrefMedlineGoogle Scholar3 Ballo P, Mondillo S, Galderisi M. Determinants of discrepancy between left ventricular chamber systolic performance and effective myocardial contractility in subjects with hypertension. J Hum Hypertens. 2006; 20: 701–703.CrossrefMedlineGoogle Scholar4 Ding B, Price RL, Goldsmith EC, Borg TK, Yan X, Douglas PS, Weinberg EO, Bartunek J, Thielen T, Didenko VV, Lorell BH. Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure. Circulation. 2000; 101: 2854–2862.CrossrefMedlineGoogle Scholar5 Mori T, Chen YF, Feng JA, Hayashi T, Oparil S, Perry GJ. Volume overload results in exaggerated cardiac hypertrophy in the atrial natriuretic peptide knockout mouse. Cardiovasc Res. 2004; 61: 771–779.CrossrefMedlineGoogle Scholar6 Takimoto E, Soergel DG, Janssen PM, Stull LB, Kass DA, Murphy AM. Frequency- and afterload-dependent cardiac modulation in vivo by troponin I with constitutively active protein kinase A phosphorylation sites. Circ Res. 2004; 94: 496–504.LinkGoogle Scholar7 Williams RV, Lorenz JN, Witt SA, Hellard DT, Khoury PR, Kimball TR. End-systolic stress-velocity and pressure-dimension relationships by transthoracic echocardiography in mice. Am J Physiol. 1998; 274: H1828–H1835.MedlineGoogle Scholar8 Connelly KA, Prior DL, Kelly DJ, Feneley MP, Krum H, Gilbert RE. Load-sensitive measures may overestimate global systolic function in the presence of left ventricular hypertrophy: a comparison with load-insensitive measures. Am J Physiol Heart Circ Physiol. 2006; 290: H1699–H1705.CrossrefMedlineGoogle Scholar9 Ballo P, Mondillo S, Motto A, Faraguti SA. Left ventricular midwall mechanics in subjects with aortic stenosis and normal systolic chamber function. J Heart Valve Dis. 2006; 15: 639–650.MedlineGoogle Scholar10 Kim YK, Suarez J, Hu Y, McDonough PM, Boer C, Dix DJ, Dillmann WH. Deletion of the inducible 70-kDa heat shock protein genes in mice impairs cardiac contractile function and calcium handling associated with hypertrophy. Circulation. 2006; 113: 2589–2597.LinkGoogle Scholar11 Ballo P, Mondillo S, Guerrini F, Barbati R, Picchi A, Focardi M. Midwall mechanics in physiologic and hypertensive concentric hypertrophy. J Am Soc Echocardiogr. 2004; 17: 418–427.CrossrefMedlineGoogle Scholar12 Mondillo S, Galderisi M, Ballo P, Marino PN; Study Group of Echocardiography of the Italian Society of Cardiology. Left ventricular systolic longitudinal function: comparison among simple M-mode, pulsed, and M-mode color tissue Doppler of mitral annulus in healthy individuals. J Am Soc Echocardiogr. 2006; 19: 1085–1091.CrossrefMedlineGoogle Scholar13 Klein G, Schaefer A, Hilfiker-Kleiner D, Oppermann D, Shukla P, Quint A, Podewski E, Hilfiker A, Schroder F, Leitges M, Drexler H. Increased collagen deposition and diastolic dysfunction but preserved myocardial hypertrophy after pressure overload in mice lacking PKCepsilon. Circ Res. 2005; 96: 748–755.LinkGoogle Scholar14 Sebag IA, Handschumacher MD, Ichinose F, Morgan JG, Hataishi R, Rodrigues AC, Guerrero JL, Steudel W, Raher MJ, Halpern EF, Derumeaux G, Bloch KD, Picard MH, Scherrer-Crosbie M. Quantitative assessment of regional myocardial function in mice by tissue Doppler imaging: comparison with hemodynamics and sonomicrometry. Circulation. 2005; 111: 2611–2616.LinkGoogle Scholar15 Ballo P, Quatrini I, Giacomin E, Motto A, Mondillo S. Circumferential versus longitudinal function in patients with hypertension: a nonlinear relation. J Am Soc Echocard. 2007. In press.Google Scholar16 Neilan TG, Jassal DS, Perez-Sanz TM, Raher MJ, Pradhan AD, Buys ES, Ichinose F, Bayne DB, Halpern EF, Weyman AE, Derumeaux G, Bloch KD, Picard MH, Scherrer-Crosbie M. Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury. Eur Heart J. 2006; 27: 1868–1875.CrossrefMedlineGoogle Scholar17 Carlsson M, Ugander M, Mosen H, Buhre T, Arheden H Atrioventricular plane displacement is the major contributor to left ventricular pumping in healthy adults, athletes and patients with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol. 2006 Nov 10. In press.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Kumari R, Ray A, Mukherjee D, Chander V, Kar D, Kumar U, Bharadwaj P.V.P. D, Banerjee S, Konar A and Bandyopadhyay A (2022) Downregulation of PTEN Promotes Autophagy via Concurrent Reduction in Apoptosis in Cardiac Hypertrophy in PPAR α−/− Mice, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2022.798639, 9 February 16, 2007Vol 100, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/01.RES.0000259102.33446.65PMID: 17307965 Originally publishedFebruary 16, 2007 PDF download Advertisement