Gene delivery of sarcoplasmic reticulum calcium ATPase inhibits ventricular remodeling in ischemic mitral regurgitation
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Background—: Mitral regurgitation (MR) doubles mortality after myocardial infarction (MI). We have demonstrated that MR worsens remodeling after MI and that early correction reverses remodeling. Sarcoplasmic reticulum Ca +2 -ATPase (SERCA2a) is downregulated in this process. We hypothesized that upregulating SERCA2a might inhibit remodeling in a surgical model of apical MI (no intrinsic MR) with independent MR-type flow. Methods and Results—: In 12 sheep, percutaneous gene delivery was performed by using a validated protocol to perfuse both the left anterior descending and circumflex coronary arteries with occlusion of venous drainage. We administered adeno-associated virus 6 (AAV6) carrying SERCA2a under a Cytomegalovirus promoter control in 6 sheep and a reporter gene in 6 controls. After 2 weeks, a standardized apical MI was created, and a shunt was implanted between the left ventricle and left atrium, producing regurgitant fractions of ≈30%. Animals were compared at baseline and 1 and 3 months by 3D echocardiography, Millar hemodynamics, and biopsies. The SERCA2a group had a well-maintained preload-recruitable stroke work at 3 months (decrease by 8±10% vs 42±12% with reporter gene controls; P <0.001). Left ventricular dP/dt followed the same pattern (no change vs 55% decrease; P <0.001). Left ventricular end-systolic volume was lower with SERCA2a (82.6±9.6 vs 99.4±9.7 mL; P =0.03); left ventricular end-diastolic volume, reflecting volume overload, was not significantly different (127.8±6.2 vs 134.3±9.4 mL). SERCA2a sheep showed a 15% rise in antiapoptotic pAkt versus a 30% reduction with the reporter gene ( P <0.001). Prohypertrophic activated STAT3 was also 41% higher with SERCA2a than in controls ( P <0.001). Proapoptotic activated caspase-3 rose >5-fold during 1 month in both SERCA2a and control animals ( P =NS) and decreased by 19% at 3 months, remaining elevated in both groups. Conclusions—: In this controlled model, upregulating SERCA2a induced better function and lesser remodeling, with improved contractility, smaller volume, and activation of prohypertrophic/antiapoptotic pathways. Although caspase-3 remained activated in both groups, SERCA2a sheep had increased molecular antiremodeling “tone.” We therefore conclude that upregulating SERCA2a inhibits MR-induced post-MI remodeling in this model and thus may constitute a useful approach to reduce the vicious circle of remodeling in ischemic MR.
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Transduction of sheep myocardium with AAV vectors such as AAV-6 and AAV-2/1 has been successfully performed with techniques such as coronary infusion coupled with brief coronary and venous blockage and re-circulating systems.
“Transduction of sheep myocardium with AAV vectors (such as AAV-6 and AAV-2/1) have been successfully performed with techniques such as coronary infusion coupled with brief coronary and venous blockage (Beeri, et al., 2010) and re-circulating systems (Byrne, et al., 2008; J. D. White, et al., 2011) which target the myocardium directly and increase exposure time.”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Beeri, et al., 2010
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Zoghbi, W. A., Enriquez-Sarano, M. L., Foster, E., Grayburn, P. A., Kraft, C. D., Levine, R. A., Nihoyannopoulos, P., Otto, C. M., Quiñones, M. A., Rakowski, H., et al. (2003) · Journal of the American Society of Echocardiography · doi:10.1016/s0894-7317(03)00335-3 · Cited by 4,041 · see citing works
Self-citationPfeffer, M. A., & Braunwald, E. (1990) · Circulation · doi:10.1161/01.cir.81.4.1161 · Cited by 2,874 · see citing works
Cohn, J. N., Ferrari, R., & Sharpe, N. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00630-0 · Cited by 2,591 · see citing works
Glower, D. D., Spratt, J. A., Snow, N. D., Kabas, J. S., Davis, J. W., Olsen, C. O., Tyson, G. S., Sabiston, D. C., & Rankin, J. S. (1985) · Circulation · doi:10.1161/01.cir.71.5.994 · Cited by 857 · see citing works
Cytoplasmic signaling pathways that regulate cardiac hypertrophy.
Molkentin, J., & Dorn, G. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.391 · Cited by 760 · see citing works
Clinical Outcome of Mitral Regurgitation Due to Flail Leaflet
Ling, L. H., Enriquez-Sarano, M. L., Seward, J. B., Tajik, A. J., Schaff, H. V., Bailey, K. R., & Frye, R. L. (1996) · New England Journal of Medicine · doi:10.1056/nejm199611073351902 · Cited by 661 · see citing works
Otsuji, Y., Handschumacher, M. D., Schwammenthal, E., Jiang, L., Song, J., Guerrero, J., Vlahakes, G. J., & Levine, R. A. (1997) · Circulation · doi:10.1161/01.cir.96.6.1999 · Cited by 592 · see citing works
Self-citationMiyamoto, M. I., del Monte, F., Schmidt, U. H., DiSalvo, T. S., Kang, Z. B., Matsui, T., Guerrero, J. L., Gwathmey, J. K., Rosenzweig, A., & Hajjar, R. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.793 · Cited by 528 · see citing works
Self-citationdel Monte, F., Harding, S. E., Schmidt, U., Matsui, T., Kang, Z. B., Dec, G. W., Gwathmey, J. K., Rosenzweig, A., & Hajjar, R. J. (1999) · Circulation · doi:10.1161/01.cir.100.23.2308 · Cited by 502 · see citing works
Self-citationJaski, B. E., Jessup, M. L., Mancini, D. M., Cappola, T. P., Pauly, D. F., Greenberg, B., Borow, K., Dittrich, H., Zsebo, K. M., & Hajjar, R. J. (2009) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2009.01.013 · Cited by 457 · see citing works
Self-citationMechanism of Recurrent Ischemic Mitral Regurgitation After Annuloplasty
Hung, J., Papakostas, L., Tahta, S. A., Hardy, B. G., Bollen, B. A., Durán, C. M. G., & Levine, R. A. (2004) · Circulation · doi:10.1161/01.cir.0000138192.65015.45 · Cited by 444 · see citing works
Self-citationHasenfuss, G. P., Schillinger, W., Lehnart, S. E., Preuss, M. H., Pieske, B. M., Maier, L. S., Prestle, J., Minami, K., & Just, H. (1999) · Circulation · doi:10.1161/01.cir.99.5.641 · Cited by 409 · see citing works
del Monte, F., Williams, E., Lebeche, D., Schmidt, U., Rosenzweig, A., Gwathmey, J. K., Lewandowski, E. D., & Hajjar, R. J. (2001) · Circulation · doi:10.1161/hc3601.095574 · Cited by 382 · see citing works
Self-citationKawase, Y., Ly, H. Q., Prunier, F., Lebeche, D., Shi, Y., Jin, H., Hadri, L., Yoneyama, R., Hoshino, K., Takewa, Y., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.12.014 · Cited by 343 · see citing works
Self-citationOtsuji, Y., Handschumacher, M. D., Liel‐Cohen, N., Tanabe, H., Jiang, L., Schwammenthal, E., Guerrero, J., Nicholls, L. A., Vlahakes, G. J., & Levine, R. A. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)01134-7 · Cited by 311 · see citing works
Self-citationModulation of ventricular function through gene transfer in vivo
Hajjar, R. J., Schmidt, U. H., Matsui, T., Guerrero, J. L., Lee, K.-H., Gwathmey, J. K., DEC, G. W., Semigran, M. J., & Rosenzweig, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5251 · Cited by 294 · see citing works
Self-citationGwathmey, J. K., Slawsky, M., Hajjar, R. J., Briggs, G. M., & Morgan, J. P. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114611 · Cited by 271 · see citing works
Self-citationLiel‐Cohen, N., Guerrero, J. L., Otsuji, Y., Handschumacher, M. D., Rudski, L., Hunziker, P., Tanabe, H., Scherrer‐Crosbie, M., Sullivan, S. M., & Levine, R. A. (2000) · Circulation · doi:10.1161/01.cir.101.23.2756 · Cited by 233 · see citing works
Self-citationSchmidt, U., del Monte, F., Miyamoto, M. I., Matsui, T., Gwathmey, J. K., Rosenzweig, A., & Hajjar, R. J. (2000) · Circulation · doi:10.1161/01.cir.101.7.790 · Cited by 230 · see citing works
Self-citationdel Monte, F., Lebeche, D., Guerrero, J. L., Tsuji, T., Doye, A. A., Gwathmey, J. K., & Hajjar, R. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305778101 · Cited by 217 · see citing works
Self-citationAltered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy?
Sipido, K. R. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00470-9 · Cited by 214 · see citing works
Schmidt, U. H., Hajjar, R. J., Helm, P. A., Kim, C. S., Doye, A. A., & Gwathmey, J. K. (1998) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1998.0748 · Cited by 209 · see citing works
Self-citationLarge animal model of ischemic mitral regurgitation
Llaneras, M. R., Nance, M. L., Streicher, J. T., Lima, J. A. C., Savino, J. S., Bogen, D. K., Deac, R. F. P., Ratcliffe, M. B., & Edmunds, L. H. (1994) · The Annals of Thoracic Surgery · doi:10.1016/0003-4975(94)91012-x · Cited by 168 · see citing works
Handschumacher, M. D., Lethor, J. P., Siu, S. C., Mele, D., Rivera, J. M., Picard, M. H., Weyman, A. E., & Levine, R. A. (1993) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(93)90108-d · Cited by 161 · see citing works
Self-citationReverse Ventricular Remodeling Reduces Ischemic Mitral Regurgitation
Hung, J., Guerrero, J., Handschumacher, M. D., Supple, G. E., Sullivan, S. M., & Levine, R. A. (2002) · Circulation · doi:10.1161/01.cir.0000038363.83133.6d · Cited by 150 · see citing works
Self-citationRoles of Adeno-Associated Virus Rep Protein and Human Chromosome 19 in Site-Specific Recombination
Young, S., McCarty, D. M., Degtyareva, N. P., & Samulski, R. J. (2000) · Journal of Virology · doi:10.1128/jvi.74.9.3953-3966.2000 · Cited by 138 · see citing works
Efficiency of eight different AAV serotypes in transducing rat myocardium in vivo
Palomeque, J., Chemaly, E. R., Colosi, P., Wellman, J. A., Zhou, S. Z., del Monte, F., & Hajjar, R. J. (2007) · Gene Therapy · doi:10.1038/sj.gt.3302895 · Cited by 135 · see citing works
Self-citationSakata, S., Lebeche, D., Sakata, N., Sakata, Y., Chemaly, E. R., Liang, L. F., Tsuji, T., Takewa, Y., del Monte, F., PELUSO, R. W., et al. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.01.003 · Cited by 126 · see citing works
Self-citationSpinale, F. G., Ishihra, K., Zile, M. R., DeFryte, G., Crawford, F. A., & Carabello, B. A. (1993) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(19)33992-3 · Cited by 111 · see citing works
Infarct Size And Location Determine Development Of Mitral Regurgitation In The Sheep Model
Gorman, J. H., Gorman, R. C., Plappert, T. A., Jackson, B. M., Hiramatsu, Y., John-Sutton, M. G. S., & Edmunds, L. H. (1998) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(98)70326-5 · Cited by 109 · see citing works
Left ventricular function in experimental volume overload hypertrophy
Carabello, B. A., Nakano, K., Corin, W. J., Biederman, R. W., & Spann, J. F. (1989) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1989.256.4.h974 · Cited by 100 · see citing works
Ito, K. I., Yan, X., Tajima, M., Su, Z. G., Barry, W. H., & Lorell, B. H. (2000) · Circulation Research · doi:10.1161/01.res.87.7.588 · Cited by 94 · see citing works
Mitral Regurgitation Augments Post-Myocardial Infarction Remodeling
Beeri, R., Yosefy, C., Guerrero, J., Delling, F. N., Abedat, S., Chaput, M., del Monte, F., Handschumacher, M. D., Stroud, R. E., Sullivan, S. M., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.07.093 · Cited by 90 · see citing works
Self-citationChu, A. H., Dixon, M. C., Saito, A., Seiler, S. M., & Fleischer, S. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(88)57066-0 · Cited by 89 · see citing works
Davia, K., Bernobich, E., Ranu, H., del Monte, F., Terracciano, C. M., MacLeod, K. T., Adamson, D. L., Chaudhri, B. B., Hajjar, R. J., & Harding, S. E. (2001) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2001.1368 · Cited by 89 · see citing works
Self-citationSakata, Y., Masuyama, T., Yamamoto, K., Nishikawa, N., Yamamoto, H., Kondo, H., Ono, K., Otsu, K., Kuzuya, T., Miwa, T., et al. (2000) · Circulation · doi:10.1161/01.cir.102.18.2269 · Cited by 84 · see citing works
Moainie, S. L., Guy, T. S., Gorman, J. H., Plappert, T. A., Jackson, B. M., John-Sutton, M. G. S., Edmunds, L. H., & Gorman, R. C. (2002) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(02)03747-5 · Cited by 75 · see citing works
Na/Ca Exchange in Heart Failure
Pogwizd, S. M., & Bers, D. M. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04775.x · Cited by 73 · see citing works
Sakata, S., Lebeche, D., Sakata, Y., Sakata, N., Chemaly, E. R., Liang, L., Nakajima‐Takenaka, C., Tsuji, T., Konishi, N., del Monte, F., et al. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00892.2006 · Cited by 71 · see citing works
Self-citationNew Efficient Catheter-Based System for Myocardial Gene Delivery
Beeri, R., Guerrero, J. L., Supple, G. E., Sullivan, S. M., Levine, R. A., & Hajjar, R. J. (2002) · Circulation · doi:10.1161/01.cir.0000035240.92015.e4 · Cited by 70 · see citing works
Self-citationSERCA2a in Heart Failure: Role and Therapeutic Prospects
Gianni, D., Chan, J., Gwathmey, J. K., del Monte, F., & Hajjar, R. J. (2005) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-005-9474-z · Cited by 65 · see citing works
Self-citationEarly Repair of Moderate Ischemic Mitral Regurgitation Reverses Left Ventricular Remodeling
Beeri, R., Yosefy, C., Guerrero, J., Abedat, S., Handschumacher, M. D., Stroud, R. E., Sullivan, S. M., Chaput, M., Gilon, D., Vlahakes, G. J., et al. (2007) · Circulation · doi:10.1161/circulationaha.106.681114 · Cited by 64 · see citing works
Self-citationPapillary muscle–left ventricular wall “complex”
Komeda, M., Glasson, J. R., Bolger, A. F., Daughters, G. T., Ingels, N. B., & Miller, D. C. (1997) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(97)70326-x · Cited by 55 · see citing works
Kinetics of Recombinant Adeno-Associated Virus-Mediated Gene Transfer
Malik, A. K., Monahan, P. E., Allen, D. L., Chen, B.-G., Samulski, R. J., & Kurachi, K. (2000) · Journal of Virology · doi:10.1128/jvi.74.8.3555-3565.2000 · Cited by 48 · see citing works
Ernst Schering Research Foundation Workshop
Lessl, M., & Chwalisż, K. (2010) · Cited by 41 · see citing works
Faulk, E. A., McCully, J. D., Tsukube, T., Hadlow, N. C., Krukenkamp, I. B., & Levitsky, S. (1995) · The Annals of Thoracic Surgery · doi:10.1016/0003-4975(95)00446-r · Cited by 37 · see citing works
Sakata, S., Lebeche, D., Sakata, N., Sakata, Y., Chemaly, E. R., Liang, L. F., Takewa, Y., Jeong, D., Park, W. J., Kawase, Y., et al. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01310.2006 · Cited by 36 · see citing works
Self-citationSandalon, Z., Bruckheimer, E. M., Lustig, K., Rogers, L. C., PELUSO, R. W., & Burstein, H. (2004) · Journal of Virology · doi:10.1128/jvi.78.22.12355-12365.2004 · Cited by 34 · see citing works
Enriquez-Sarano, M. L., Loulmet, D. F., & Burkhoff, D. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.09.046 · Cited by 27 · see citing works
Picard, M. H., WILKINS, G. T., Ray, P. A., & Weyman, A. E. (1992) · American Heart Journal · doi:10.1016/0002-8703(92)90916-j · Cited by 24 · see citing works
AAV Vectors, the Future Workhorse of Human Gene Therapy
Samulski, R. J. (2003) · Springer eBooks · doi:10.1007/978-3-662-05352-2_3 · Cited by 19 · see citing works
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- [33]Kawase Y Ly HQ Prunier F Lebeche D Shi Y Jin H Hadri L Yoneyama R Hoshino K Takewa Y Sakata S Peluso R Zsebo K Gwathmey JK Tardif JC Tanguay JF Hajjar RJ Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure J Am Coll Cardiol 2008 51 1112 1119 18342232
- [43]del Monte F Williams E Lebeche D Schmidt U Rosenzweig A Gwathmey JK Lewandowski ED Hajjar RJ Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase in a rat model of heart failure Circulation 2001 104 1424 1429 11560860 PMC1249503
- [48]Sakata S Lebeche D Sakata N Sakata Y Chemaly ER Liang LF Takewa Y Jeong D Park WJ Kawase Y Hajjar RJ Targeted gene transfer increases contractility and decreases oxygen cost of contractility in normal rat hearts Am J Physiol Heart Circ Physiol 2007 292 H2356 2363 17220178
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Self-citationWinter, J., Brack, K. E., & Ng, G. A. (2011) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfr042 · Cited by 26 · see citing works
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Cui, X., Guo, J., Yuan, P., Dai, Y., Du, P., Yu, F., Sun, Z., Zhang, J., Cheng, K., & Tang, J. (2024) · ACS Nano · doi:10.1021/acsnano.3c07878 · Cited by 27 · see citing works
Nagai, T., & Komuro, I. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00130.2012 · Cited by 23 · see citing works
Experimental Models of Cardiovascular Diseases: Overview
Oh, J. G., & Ishikawa, K. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8597-5_1 · Cited by 23 · see citing works
Mazurek, R., Tharakan, S., Mavropoulos, S. A., Singleton, D. T., Bikou, O., Sakata, T., Kariya, T., Yamada, K. P., Kohlbrenner, E., Liang, L., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54635-x · Cited by 21 · see citing works
Self-citationVinogradova, T. M., Tagirova, S., & Lakatta, E. G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082173 · Cited by 21 · see citing works
Gene Therapy for Heart Failure: Where Do We Stand?
Naim, C., Yerevanian, A. I., & Hajjar, R. J. (2013) · Current Cardiology Reports · doi:10.1007/s11886-012-0333-3 · Cited by 20 · see citing works
Self-citationChaanine, A. H., Kalman, J., & Hajjar, R. J. (2010) · Seminars in Thoracic and Cardiovascular Surgery · doi:10.1053/j.semtcvs.2010.09.009 · Cited by 19 · see citing works
Self-citationPotential targets of gene therapy in the treatment of heart failure
Rosik, J., Szostak, B., Machaj, F., & Pawlik, A. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1514012 · Cited by 18 · see citing works
Bonsu, K. O., Owusu, I. K., Buabeng, K. O., Reidpath, D. D., & Kadirvelu, A. (2016) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s106065 · Cited by 16 · see citing works
Bobe, E. R. C. R. (2013) · Journal of Cardiovascular Diseases & Diagnosis · doi:10.4172/2329-9517.1000113 · Cited by 16 · see citing works
Does Taurine Prolong Lifespan by Improving Heart Function?
Schaffer, S. W., Ramila, K. C., Jong, C. J., Shetewy, A., Shimada, K., Ito, T., Azuma, J., & Cioffi, E. A. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-15126-7_45 · Cited by 15 · see citing works
The cardiotoxic effects of acute and chronic grayanotoxin-III in rats
Doğanyiğit, Z., Kaymak, E., & Sılıcı, S. (2019) · Human & Experimental Toxicology · doi:10.1177/0960327119889668 · Cited by 12 · see citing works
Model‐specific selection of molecular targets for heart failure gene therapy
Katz, M. G., Fargnoli, A. S., Tomasulo, C. E., Pritchette, L. A., & Bridges, C. R. (2011) · The Journal of Gene Medicine · doi:10.1002/jgm.1610 · Cited by 11 · see citing works
Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases
Bera, A., & Sen, D. (2017) · Heart Failure Reviews · doi:10.1007/s10741-017-9622-7 · Cited by 10 · see citing works
Sarcoendoplasmic Reticulum Calcium Transport ATPase 2a
Papolos, A., & Frishman, W. H. (2012) · Cardiology in Review · doi:10.1097/crd.0b013e3182749cdb · Cited by 9 · see citing works
Farraha, M., Barry, M. A., Lu, J., Pouliopoulos, J., Le, T. Y. L., Igoor, S., Rao, R., Kok, C., Chong, J. J. H., & Kizana, E. (2019) · Gene Therapy · doi:10.1038/s41434-019-0097-0 · Cited by 8 · see citing works
Gene therapy for heart disease: molecular targets, vectors and modes of delivery to myocardium
Scimia, M. C., Cannavò, A., & Koch, W. J. (2013) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.2013.818813 · Cited by 8 · see citing works
Wang, J., Jonker, T., Cervera-Barea, A., Dong, Z., Visser, R. N., Birza, E. E., Boender, A., Klerk, M., Yang, Y., Visser, J., et al. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101532 · Cited by 8 · see citing works
Changes in cardiac structure and function in a modified rat model of myocardial hypertrophy
Dai, W., Dong, Q., Chen, M., Zhao, L., Chen, A., Li, Z., & Liu, S. (2016) · Cardiovascular journal of South Africa/Cardiovascular journal of Southern Africa · doi:10.5830/cvja-2015-053 · Cited by 7 · see citing works
AAV-mediated gene therapy for heart failure: enhancing contractility and calcium handling
Zouein, F. A., & Booz, G. W. (2013) · F1000Prime Reports · doi:10.12703/p5-27 · Cited by 7 · see citing works
Status of Therapeutic Gene Transfer to Treat Cardiovascular Disease in Dogs and Cats
Sleeper, M. M. (2017) · Veterinary Clinics of North America Small Animal Practice · doi:10.1016/j.cvsm.2017.04.005 · Cited by 7 · see citing works
Alterations in cardiac structure and function in a modified rat model of myocardial hypertrophy
Dai, W., Dong, Q., Chen, M., Zhao, L., Chen, A., Li, Z., & Liu, S. (2014) · Journal of Huazhong University of Science and Technology [Medical Sciences] · doi:10.1007/s11596-014-1328-7 · Cited by 5 · see citing works
Rapti, K., Hajjar, R. J., & Weber, T. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-891-7_12 · Cited by 4 · see citing works
Self-citationGene Therapy in Cardiovascular Disease
Reyes-Juárez, J. L., & Zarain‐Herzberg, Á. (2011) · InTech eBooks · doi:10.5772/17429 · Cited by 2 · see citing works
Apilarnil protects the LPS induced endotoxemic heart
Okan, A., Kaymak, E., Üner, A. K., Sılıcı, S., & Doğanyiğit, Z. (2022) · Turkish Bulletin of Hygiene and Experimental Biology · doi:10.5505/turkhijyen.2022.78200 · Cited by 2 · see citing works
Anticipating the Vicious Circle of Postinfarction Mitral Regurgitation
Dal‐Bianco, J. P., Bartko, P. E., & Levine, R. A. (2016) · Circulation Cardiovascular Imaging · doi:10.1161/circimaging.116.005070 · Cited by 2 · see citing works
Self-citationTranscatheter Mitral Valve Therapies
Schwartzenberg, S., Yosefy, C., & Sagie, A. (2021) · doi:10.1002/9781119763741.ch4 · Cited by 2 · see citing works
Self-citationBiologics for cardiovascular diseases: from bench to bedside
Sun, X., Wang, X., Jia, R., Tang, J., Zeng, X. Y., Zhao, F., Zeng, F., Huang, N., Li, J., & Cui, K. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02673-w · Cited by 2 · see citing works
Gene Therapy for Cardiovascular Diseases
Weber, T., Zangi, L., & Hajjar, R. J. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801888-0.00029-1 · Cited by 1 · see citing works
Self-citationGene- and Cell-Based Therapy for Cardiovascular Disease
Marı́n-Garcı́a, J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-404599-6.00023-8 · Cited by 1 · see citing works
Circulation: Heart Failure Editors' Picks
Kociol, R. D. (2012) · Circulation Heart Failure · doi:10.1161/circheartfailure.112.967463 · Cited by 1 · see citing works
Probing cardiac calcium regulation using time-resolved optical spectroscopy.
Li, J. (2012) · University of Minnesota Digital Conservancy (University of Minnesota) · Cited by 1 · see citing works
Gene Transfer of the Sarcoplasmic Reticulum Pump in the Treatment of Heart Failure
Hasenfuss, G. P. (2011) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfr008
SERCA2a Gene Therapy for Heart Failure
Chaanine, A. H., Yaroshinsky, A., & Hajjar, R. J. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801888-0.00030-8
Self-citationRecombinant Adeno-Associated Virus for Cardiac Gene Therapy
Kok, C., Ravindran, D., & Kizana, E. (2022) · Springer eBooks · doi:10.1007/978-3-030-86140-7_9
Valvular Heart Disease in Circulation and the Circulation Subspecialty Journals
Editors, T. (2012) · Circulation · doi:10.1161/circulationaha.112.115501
Circulation: Heart Failure Editors' Picks
Editors, T. (2011) · Circulation · doi:10.1161/circulationaha.111.046425
TBHEB 2022-4 Vol 79 Full Printed Journal
ERCÖMERT, U. (2022) · Turkish Bulletin of Hygiene and Experimental Biology · doi:10.5505/turkhijyen.2022.81226
Adeno-associated virus (AAV)-TBX18 does not generate biological pacemaker activity, unlike AAV-Hcn2Preprint
Wang, J., Rivaud, M. R., Klerk, M., Boender, A., Visser, R. N., Sparrius, R., Lee, H., van Duijvenboden, K., Yang, Y., Kramer, E. J. M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.11.672351
Singh, I., Kumar, A., Chaudhary, A. K., Dalal, J. S., Sharma, A., Sharma, J., Ratn, A., Dhakad, M. S., & Sharma, D. (2026) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/14703203261437332
- Authors
- Beeri, R., Chaput, M., Guerrero, J. L., Kawase, Y., Yosefy, C., Abedat, S., Karakikes, I., Morel, C., Tisosky, A., Sullivan, S., Handschumacher, M. D., Gilon, D., Vlahakes, G. J., Hajjar, R. J., & Levine, R. A.
- Affiliations
- From the Cardiac Ultrasound Laboratory and Cardiac Surgery Department (R.B., M.C., J.L.G., Y.K., C.Y., S.S., M.D.H., G.J.V., R.A.L.), Heart Center, Massachusetts General Hospital, Boston, Mass; Cardiovascular Research Center (R.B., S.A., D.G.), Heart Institute, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; and the Cardiovascular Research Center (J.K., C.M., A.T., R.J.H.), Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY.
- Mount Sinai Hospital (US)
- ORCID
- Venue
- Circulation: Heart Failure
- Published
- 2010-09
- Volume
- 3
- Issue
- 5
- Pages
- 627-634
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- PMC
- PMC2939951
- OpenAlex
- W2080482562
- Cited by
- 69
- References
- 51
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2022: 3 · 2021: 1 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 10 · 2012: 9
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01 HL72265, K24HL067434, R01HL080498, K24 HL67434, R01HL072265, R01HL078731, R01HL083156)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Surgery › Cardiac Structural Anomalies and Repair
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Keywords
- SERCA2a, sarcoplasmic reticulum calcium ATPase, ventricular remodeling, ischemic mitral regurgitation, gene therapy, myocardial infarction, left ventricular remodeling, apoptosis, caspase-3, STAT3, pAKT, sheep model, left ventricular function, myocardial fibrosis, cardiomyocyte hypertrophy
- MeSH terms
- Dependovirus, Analysis of Variance, Animals, Cytomegalovirus, Disease Models, Animal, Male, Mitral Valve Insufficiency, Promoter Regions, Genetic, Sheep, Genetic Therapy, Up-Regulation, Gene Expression Regulation, Enzymologic, Myocardial Ischemia, Genes, Reporter, Gene Transfer Techniques, Echocardiography, Doppler, Color, Ventricular Remodeling, Sarcoplasmic Reticulum Calcium-Transporting ATPases
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