Skip to main content

Advertisement

SpringerLink
Log in

Silencing Survivin: a Key Therapeutic Strategy for Cardiac Hypertrophy

  • Original Article
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Cardiac hypertrophy, in its aspects of localized thickening of the interventricular septum and concentric increase of the left ventricle, constitutes a risk factor of heart failure. Myocardial hypertrophy, in the presence of different degree of myocardial fibrosis, is paralleled by significant molecular, cellular, and histological changes inducing alteration of cardiac extracellular matrix composition as well as sarcomeres and cytoskeleton remodeling. Previous studies indicate osteopontin (OPN) and more recently survivin (SURV) overexpression as the hallmarks of heart failure although SURV function in the heart is not completely clarified. In this study, we investigated the involvement of SURV in intracellular signaling of hypertrophic cardiomyocytes and the impact of its transcriptional silencing, laying the foundation for novel target gene therapy in cardiac hypertrophy. Oligonucleotide-based molecules, like theranostic optical nanosensors (molecular beacons) and siRNAs, targeting SURV and OPN mRNAs, were developed. Their diagnostic and therapeutic potential was evaluated in vitro in hypertrophic FGF23-induced human cardiomyocytes and in vivo in transverse aortic constriction hypertrophic mouse model. Engineered erythrocyte was used as shuttle to selectively target and transfer siRNA molecules into unhealthy cardiac cells in vivo. The results highlight how the SURV knockdown could negatively influence the expression of genes involved in myocardial fibrosis in vitro and restores structural, functional, and morphometric features in vivo. Together, these data suggested that SURV is a key factor in inducing cardiomyocytes hypertrophy, and its shutdown is crucial in slowing disease progression as well as reversing cardiac hypertrophy. In the perspective, targeted delivery of siRNAs through engineered erythrocytes can represent a promising therapeutic strategy to treat cardiac hypertrophy.

Graphical abstract

Theranostic SURV molecular beacon (MB-SURV), transfected into FGF23-induced hypertrophic human cardiomyocytes, significantly dampened SURV overexpression. SURV down–regulation determines the tuning down of MMP9, TIMP1 and TIMP4 extracellular matrix remodeling factors while induces the overexpression of the cardioprotective MCAD factor, which counterbalance the absence of pro-survival and anti-apoptotic SURV activity to protect cardiomyocytes from death. In transverse aortic constriction (TAC) mouse model, the SURV silencing restores the LV mass levels to values not different from the sham group and counteracts the progressive decline of EF, maintaining its values always higher with respect to TAC group. These data demonstrate the central role of SURV in the cardiac reverse remodeling and its therapeutic potential to reverse cardiac hypertrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

ANP:

Atrial natriuretic peptide

BBQ:

Blackberry Quencher 650

β-MHC:

Beta- myosin heavy chain

BNP:

Brain natriuretic peptide

CLSM:

Confocal laser scanning microscopy

CSA:

Cross-sectional area

EF:

Ejection fraction

EGR1:

Early growth response 1

EMHV:

Erythro-Magneto-Ha virosome

ERK:

Extracellular signal-regulated kinases

FGF23:

Fibroblast growth factor 23

FHA:

Filamentous hemagglutinin

FS:

Fractional shortening

GADPH:

Glyceraldehyde-3-phosphate dehydrogenase

HCM:

Human cardiomyocyte

HF:

Heart failure

HRP:

Horseradish peroxidase

HW:

Heart weight

IHC:

Immunohistochemistry

IVSTd :

Interventricular septum thickness, diastolic

LC:

Left carotid

LV:

Left ventricle

LVAD:

Left ventricular assist device

LVPWTd :

Left ventricle posterior wall thickness, diastolic

MB:

Molecular beacon

MCAD:

Medium-chain acyl-CoA dehydrogenase

MMP:

Matrix metalloproteinase

NO:

Nitric oxide

NOX4:

NADPH oxidase 4

OPN:

Osteopontin

PFS:

Pixel fluorescence signal

RC:

Right carotid

sk-α-actin:

Skeletal-alpha-actin

SPION:

Super-paramagnetic iron oxide nanoparticles

SURV:

Survivin

TAC:

Transverse aortic constriction

TIMP:

Tissue inhibitor of metalloproteinase

TL:

Tibia length

UHFUS:

Ultra high-frequency ultrasound

References

  1. Brilla, C. G., Janicki, J. S., & Weber, K. T. (1991). Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries. Circulation Research, 69, 107–115. https://doi.org/10.1161/01.res.69.1.107

    Article  CAS  PubMed  Google Scholar 

  2. Ho, C. Y., López, B., Coelho-Filho, O. R., Lakdawala, N. K., Cirino, A. L., Jarolim, P., Kwong, R., González, A., Colan, S. D., Seidman, J. G., Díez, J., & Seidman, C. E. (2010). Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy. New England Journal of Medicine, 363, 552–563. https://doi.org/10.1056/NEJMoa1002659

    Article  CAS  Google Scholar 

  3. Sadoshima, J., & Izumo, S. (1997). The cellular and molecular response of cardiac myocytes to mechanical stress. Annual Review of Physiology, 59, 551–571. https://doi.org/10.1146/annurev.physiol.59.1.551

    Article  CAS  PubMed  Google Scholar 

  4. Kim, H. J., Park, M., Park, H. C., Jeong, J. C., Kim, D. K., Joo, K. W., Hwang, Y.-H., Yang, J., Ahn, C., & Oh, K.-H. (2016). Baseline Fgf23 is associated with cardiovascular outcome in incident Pd patients. Peritoneal Dialysis International, 36, 26–32. https://doi.org/10.3747/pdi.2013.00343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Saito, A., Onuki, T., Echida, Y., Otsubo, S., & Nitta, K. (2014). Fibroblast growth factor 23 and left ventricular hypertrophy in hemodialysis patients. International Journal of Clinical Medicine, 05, 1102–1110. https://doi.org/10.4236/ijcm.2014.517141

    Article  CAS  Google Scholar 

  6. Silswal, N., Touchberry, C. D., Daniel, D. R., McCarthy, D. L., Zhang, S., Andresen, J., Stubbs, J. R., & Wacker, M. J. (2014). FGF23 directly impairs endothelium-dependent vasorelaxation by increasing superoxide levels and reducing nitric oxide bioavailability. American Journal of Physiology Endocrinology and Metabolism, 307, E426–E436. https://doi.org/10.1152/ajpendo.00264.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Faul, C., Amaral, A. P., Oskouei, B., Hu, M.-C., Sloan, A., Isakova, T., Gutiérrez, O. M., Aguillon-Prada, R., Lincoln, J., Hare, J. M., Mundel, P., Morales, A., Scialla, J., Fischer, M., Soliman, E. Z., Chen, J., Go, A. S., Rosas, S. E., Nessel, L., … Wolf, M. (2011). FGF23 induces left ventricular hypertrophy. The Journal of Clinical Investigation, 121, 4393–4408. https://doi.org/10.1172/JCI46122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Touchberry, C. D., Green, T. M., Tchikrizov, V., Mannix, J. E., Mao, T. F., Carney, B. W., Girgis, M., Vincent, R. J., Wetmore, L. A., Dawn, B., Bonewald, L. F., Stubbs, J. R., & Wacker, M. J. (2013). FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy. American Journal of Physiology Endocrinology and Metabolism, 304, E863–E873. https://doi.org/10.1152/ajpendo.00596.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Datta, R., Bansal, T., Rana, S., Datta, K., Datta Chaudhuri, R., Chawla-Sarkar, M., & Sarkar, S. (2017). Myocyte-derived Hsp90 modulates collagen upregulation via biphasic activation of STAT-3 in fibroblasts during cardiac hypertrophy. Molecular and Cellular Biology, 37, e00611-e616. https://doi.org/10.1128/MCB.00611-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bendall, J. K., Heymes, C., Ratajczak, P., & Samuel, J. L. (2002). Extracellular matrix and cardiac remodelling. Archives des Maladies du Coeur et des Vaisseaux, 95, 1226–1229.

  11. Carreño, J. E., Apablaza, F., Ocaranza, M. P., & Jalil, J. E. (2006). Cardiac hypertrophy: Molecular and cellular events. Rev Española Cardiol English Ed, 59, 473–486. https://doi.org/10.1016/S1885-5857(06)60796-2

  12. Gerdes, A., & Capasso, J. (1995). Structural remodeling and mechanical dysfunction of cardiac myocytes in heart failure. Journal of Molecular and Cellular Cardiology, 27, 849–856. https://doi.org/10.1016/0022-2828(95)90000-4

    Article  CAS  PubMed  Google Scholar 

  13. Kuo, P.-L., Lee, H., Bray, M.-A., Geisse, N. A., Huang, Y.-T., Adams, W. J., Sheehy, S. P., & Parker, K. K. (2012). Myocyte shape regulates lateral registry of sarcomeres and contractility. American Journal of Pathology, 181, 2030–2037. https://doi.org/10.1016/j.ajpath.2012.08.045

    Article  CAS  Google Scholar 

  14. Sawada, K., & Kawamura, K. (1991). Architecture of myocardial cells in human cardiac ventricles with concentric and eccentric hypertrophy as demonstrated by quantitative scanning electron microscopy. Heart and Vessels, 6, 129–142. https://doi.org/10.1007/BF02058278

    Article  CAS  PubMed  Google Scholar 

  15. Bernardo, B. C., Weeks, K. L., Pretorius, L., & McMullen, J. R. (2010). Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies. Pharmacology & Therapeutics, 128, 191–227. https://doi.org/10.1016/j.pharmthera.2010.04.005

    Article  CAS  Google Scholar 

  16. Frey, N., Katus, H. A., Olson, E. N., & Hill, J. A. (2004). Hypertrophy of the heart: A new therapeutic target? Circulation, 109, 1580–1589. https://doi.org/10.1161/01.CIR.0000120390.68287.BB

    Article  PubMed  Google Scholar 

  17. Li, Y. Y., McTiernan, C. F., & Feldman, A. M. (2000). Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovascular Research, 46, 214–224. https://doi.org/10.1016/s0008-6363(00)00003-1

    Article  CAS  PubMed  Google Scholar 

  18. Parthasarathy, A., Gopi, V., Umadevi, S., Simna, A., Sheik, M. J. Y., Divya, H., & Vellaichamy, E. (2013). Suppression of atrial natriuretic peptide/natriuretic peptide receptor-A-mediated signaling upregulates angiotensin-II-induced collagen synthesis in adult cardiac fibroblasts. Molecular and Cellular Biochemistry, 378, 217–228. https://doi.org/10.1007/s11010-013-1612-z

    Article  CAS  PubMed  Google Scholar 

  19. Singh, M., Dalal, S., & Singh, K. (2014). Osteopontin: At the cross-roads of myocyte survival and myocardial function. Life Sciences, 118, 1–6. https://doi.org/10.1016/j.lfs.2014.09.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Singh, M., Foster, C. R., Dalal, S., & Singh, K. (2010). Role of osteopontin in heart failure associated with aging. Heart Failure Reviews, 15, 487–494. https://doi.org/10.1007/s10741-010-9158-6

    Article  CAS  PubMed  Google Scholar 

  21. Dalal, S., Zha, Q., Singh, M., & Singh, K. (2016). Osteopontin-stimulated apoptosis in cardiac myocytes involves oxidative stress and mitochondrial death pathway: Role of a pro-apoptotic protein BIK. Molecular and Cellular Biochemistry, 418, 1–11. https://doi.org/10.1007/s11010-016-2725-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li, Y., Li, X., Guo, S., Chu, S., Gao, P., Zhu, D., Niu, W., & Jia, N. (2013). Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin II-induced cardiac diastolic dysfunction in mice. Acta Pharmacologica Sinica, 34, 352–359. https://doi.org/10.1038/aps.2012.164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Stawowy, P., Blaschke, F., Pfautsch, P., Goetze, S., Lippek, F., Wollert-Wulf, B., Fleck, E., & Graf, K. (2002). Increased myocardial expression of osteopontin in patients with advanced heart failure. European Journal of Heart Failure, 4, 139–146. https://doi.org/10.1016/s1388-9842(01)00237-9

    Article  CAS  PubMed  Google Scholar 

  24. Li, J., Yousefi, K., Ding, W., Singh, J., & Shehadeh, L. A. (2017). Osteopontin RNA aptamer can prevent and reverse pressure overload-induced heart failure. Cardiovascular Research, 113, 633–643. https://doi.org/10.1093/cvr/cvx016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tsang, T.-J., Hsueh, Y.-C., Wei, E. I., Lundy, D. J., Cheng, B., Chen, Y.-T., Wang, S.-S., & Hsieh, P. C. H. (2017). Subcellular localization of survivin determines its function in cardiomyocytes. Theranostics, 7, 4577–4590. https://doi.org/10.7150/thno.20005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bo, L., Zhu, X.-S., Zheng, Z., Hu, X.-P., & Chen, P.-Y. (2017). Research on the function and mechanism of survivin in heart failure mice model. European Review for Medical and Pharmacological Sciences, 21, 3699–3704. https://doi.org/10.26355/eurrev_201708_13287

    Article  CAS  PubMed  Google Scholar 

  27. Si, R., Tao, L., Zhang, H. F., Yu, Q. J., Zhang, R., Lv, A. L., Zhou, N., Cao, F., Guo, W. Y., Ren, J., Wang, H. C., & Gao, F. (2011). Survivin: A novel player in insulin cardioprotection against myocardial ischemia/reperfusion injury. Journal of Molecular and Cellular Cardiology, 50, 16–24. https://doi.org/10.1016/j.yjmcc.2010.08.017

    Article  CAS  PubMed  Google Scholar 

  28. Levkau, B., Schäfers, M., Wohlschlaeger, J., von Wnuck, L. K., Keul, P., Hermann, S., Kawaguchi, N., Kirchhof, P., Fabritz, L., Stypmann, J., Stegger, L., Flögel, U., Schrader, J., Fischer, J. W., Hsieh, P., Ou, Y.-L., Mehrhof, F., Tiemann, K., Ghanem, A., … Baba, H. A. (2008). Survivin determines cardiac function by controlling total cardiomyocyte number. Circulation, 117, 1583–1593. https://doi.org/10.1161/CIRCULATIONAHA.107.734160

    Article  CAS  PubMed  Google Scholar 

  29. Wohlschlaeger, J., Meier, B., Schmitz, K. J., Takeda, A., Takeda, N., Vahlhaus, C., Levkau, B., Stypmann, J., Schmid, C., Schmid, K. W., & Baba, H. A. (2010). Cardiomyocyte survivin protein expression is associated with cell size and DNA content in the failing human heart and is reversibly regulated after ventricular unloading. J Heart Lung Transplant, 29, 1286–1292. https://doi.org/10.1016/j.healun.2010.06.015

    Article  PubMed  Google Scholar 

  30. Wohlschlaeger, J., Schmitz, K. J., Schmid, C., Schmid, K. W., Keul, P., Takeda, A., Weis, S., Levkau, B., & Baba, H. A. (2005). Reverse remodeling following insertion of left ventricular assist devices (LVAD): A review of the morphological and molecular changes. Cardiovascular Research, 68, 376–386. https://doi.org/10.1016/j.cardiores.2005.06.030

    Article  CAS  PubMed  Google Scholar 

  31. Cinti, C., Taranta, M., Naldi, I., & Grimaldi, S. (2011). Newly engineered magnetic erythrocytes for sustained and targeted delivery of anti-cancer therapeutic compounds. PLoS ONE, 6, e17132. https://doi.org/10.1371/journal.pone.0017132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Grifantini, R., Taranta, M., Gherardini, L., Naldi, I., Parri, M., Grandi, A., Giannetti, A., Tombelli, S., Lucarini, G., Ricotti, L., Campagnoli, S., De Camilli, E., Pelosi, G., Baldini, F., Menciassi, A., Viale, G., Pileri, P., & Cinti, C. (2018). Magnetically driven drug delivery systems improving targeted immunotherapy for colon-rectal cancer. Journal of Controlled Release, 280, 76–86. https://doi.org/10.1016/j.jconrel.2018.04.052

    Article  CAS  PubMed  Google Scholar 

  33. Lande, C., Cecchettini, A., Tedeschi, L., Taranta, M., Naldi, I., Citti, L., Trivella, M. G., Grimaldi, S., & Cinti, C. (2012). Innovative erythrocyte-based carriers for gene delivery in porcine vascular smooth muscle cells: Basis for local therapy to prevent restenosis. Cardiovascular & Hematological Disorders: Drug Targets, 12, 68–75. https://doi.org/10.2174/187152912801823101

    Article  CAS  Google Scholar 

  34. Lucarini, G., Sbaraglia, F., Vizzoca, A., Cinti, C., Ricotti, L., & Menciassi, A. (2020). Design of an innovative platform for the treatment of cerebral tumors by means of erythro-magneto-HA-virosomes. Biomed Phys Eng Express, 6, 45005. https://doi.org/10.1088/2057-1976/ab89f1

    Article  Google Scholar 

  35. Naldi, I., Taranta, M., Gherardini, L., Pelosi, G., Viglione, F., Grimaldi, S., Pani, L., & Cinti, C. (2014). Novel epigenetic target therapy for prostate cancer: A preclinical study. PLoS ONE, 9, e98101. https://doi.org/10.1371/journal.pone.0098101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Carpi, S., Fogli, S., Giannetti, A., Adinolfi, B., Tombelli, S., Da Pozzo, E., Vanni, A., Martinotti, E., Martini, C., Breschi, M. C., Pellegrino, M., Nieri, P., & Baldini, F. (2014). Theranostic properties of a survivin-directed molecular beacon in human melanoma cells. PLoS ONE, 9, e114588. https://doi.org/10.1371/journal.pone.0114588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nitin, N., Santangelo, P. J., Kim, G., Nie, S., & Bao, G. (2004). Peptide-linked molecular beacons for efficient delivery and rapid mRNA detection in living cells. Nucleic Acids Research, 32, e58. https://doi.org/10.1093/nar/gnh063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Langford, D. J., Bailey, A. L., Chanda, M. L., Clarke, S. E., Drummond, T. E., Echols, S., Glick, S., Ingrao, J., Klassen-Ross, T., Lacroix-Fralish, M. L., Matsumiya, L., Sorge, R. E., Sotocinal, S. G., Tabaka, J. M., Wong, D., van den Maagdenberg, A. M. J. M., Ferrari, M. D., Craig, K. D., & Mogil, J. S. (2010). Coding of facial expressions of pain in the laboratory mouse. Nature Methods, 7, 447–449. https://doi.org/10.1038/nmeth.1455

    Article  CAS  PubMed  Google Scholar 

  39. Cinti C, Lisi A, Grimaldi S (2010) Patent N. WO 2010/070620

  40. Long, C. S., Ordahl, C. P., & Simpson, P. C. (1989). Alpha 1-adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells. The Journal of Clinical Investigation, 83, 1078–1082. https://doi.org/10.1172/JCI113951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Adachi, S., Ito, H., Tamamori, M., Tanaka, M., Marumo, F., & Hiroe, M. (1998). Skeletal and smooth muscle alpha-actin mRNA in endomyocardial biopsy samples of dilated cardiomyopathy patients. Life Sciences, 63, 1779–1791. https://doi.org/10.1016/s0024-3205(98)00452-4

    Article  CAS  PubMed  Google Scholar 

  42. Heineke, J., & Molkentin, J. D. (2006). Regulation of cardiac hypertrophy by intracellular signalling pathways. Nature Reviews Molecular Cell Biology, 7, 589–600. https://doi.org/10.1038/nrm1983

    Article  CAS  PubMed  Google Scholar 

  43. Hewett, T. E., Grupp, I. L., Grupp, G., & Robbins, J. (1994). Alpha-skeletal actin is associated with increased contractility in the mouse heart. Circulation Research, 74, 740–746. https://doi.org/10.1161/01.res.74.4.740

    Article  CAS  PubMed  Google Scholar 

  44. Liew, C.-C., & Dzau, V. J. (2004). Molecular genetics and genomics of heart failure. Nature Reviews Genetics, 5, 811–825. https://doi.org/10.1038/nrg1470

    Article  CAS  PubMed  Google Scholar 

  45. Zhao, Q. D., Viswanadhapalli, S., Williams, P., Shi, Q., Tan, C., Yi, X., Bhandari, B., & Abboud, H. E. (2015). NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating Akt/mTOR and NFκB signaling pathways. Circulation, 131, 643–655. https://doi.org/10.1161/CIRCULATIONAHA.114.011079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Barger, P. M., & Kelly, D. P. (1999). Fatty acid utilization in the hypertrophied and failing heart: Molecular regulatory mechanisms. American Journal of the Medical Sciences, 318, 36–42. https://doi.org/10.1097/00000441-199907000-00006

    Article  CAS  Google Scholar 

  47. Schulz, R. (2007). Intracellular targets of matrix metalloproteinase-2 in cardiac disease: Rationale and therapeutic approaches. Annual Review of Pharmacology and Toxicology, 47, 211–242. https://doi.org/10.1146/annurev.pharmtox.47.120505.105230

    Article  CAS  PubMed  Google Scholar 

  48. Adinolfi, B., Pellegrino, M., Giannetti, A., Tombelli, S., Trono, C., Sotgiu, G., Varchi, G., Ballestri, M., Posati, T., Carpi, S., Nieri, P., & Baldini, F. (2017). Molecular beacon-decorated polymethylmethacrylate core-shell fluorescent nanoparticles for the detection of survivin mRNA in human cancer cells. Biosensors & Bioelectronics, 88, 15–24. https://doi.org/10.1016/j.bios.2016.05.102

    Article  CAS  Google Scholar 

  49. Bernardo, B. C., Weeks, K. L., Pongsukwechkul, T., Gao, X., Kiriazis, H., Cemerlang, N., Boey, E. J. H., Tham, Y. K., Johnson, C. J., Qian, H., Du, X.-J., Gregorevic, P., & McMullen, J. R. (2018). Gene delivery of medium chain acyl-coenzyme A dehydrogenase induces physiological cardiac hypertrophy and protects against pathological remodelling. Clinical Science (London, England), 132, 381–397. https://doi.org/10.1042/CS20171269

    Article  CAS  Google Scholar 

  50. Patten, R. D., & Hall-Porter, M. R. (2009). Small animal models of heart failure: Development of novel therapies, past and present. Circulation. Heart Failure, 2, 138–144. https://doi.org/10.1161/CIRCHEARTFAILURE.108.839761

    Article  PubMed  Google Scholar 

  51. Faul, C. (2017). Cardiac actions of fibroblast growth factor 23. Bone, 100, 69–79. https://doi.org/10.1016/j.bone.2016.10.001

    Article  CAS  PubMed  Google Scholar 

  52. Hammond, H. K., Penny, W. F., Traverse, J. H., Henry, T. D., Watkins, M. W., Yancy, C. W., Sweis, R. N., Adler, E. D., Patel, A. N., Murray, D. R., Ross, R. S., Bhargava, V., Maisel, A., Barnard, D. D., Lai, N. C., Dalton, N. D., Lee, M. L., Narayan, S. M., Blanchard, D. G., & Gao, M. H. (2016). Intracoronary gene transfer of adenylyl cyclase 6 in patients with heart failure: A randomized clinical trial. JAMA Cardiol, 1, 163–171. https://doi.org/10.1001/jamacardio.2016.0008

    Article  PubMed  PubMed Central  Google Scholar 

  53. Miyamoto, M. I., del Monte, F., Schmidt, U., DiSalvo, T. S., Kang, Z. B., Matsui, T., Guerrero, J. L., Gwathmey, J. K., Rosenzweig, A., & Hajjar, R. J. (2000). Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proc Natl Acad Sci U S A, 97, 793–798. https://doi.org/10.1073/pnas.97.2.793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Tevaearai, H. T., Walton, G. B., Keys, J. R., Koch, W. J., & Eckhart, A. D. (2005). Acute ischemic cardiac dysfunction is attenuated via gene transfer of a peptide inhibitor of the beta-adrenergic receptor kinase (betaARK1). The Journal of Gene Medicine, 7, 1172–1177. https://doi.org/10.1002/jgm.770

    Article  CAS  PubMed  Google Scholar 

  55. Kieserman, J. M., Myers, V. D., Dubey, P., Cheung, J. Y., & Feldman, A. M. (2019). Current landscape of heart failure gene therapy. Journal of the American Heart Association, 8, e012239. https://doi.org/10.1161/JAHA.119.012239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Silvia Burchielli for supporting animal protocol preparation and internal ethical committee.

Funding

This work was supported by National Flagship project NANOMAX-ENCODER of the Italian Ministry of Education, University and Research.

Author information

Authors and Affiliations

  1. Institute of Clinical Physiology (IFC), National Research Council of Italy (CNR), via Moruzzi 1, 56124, Pisa, Italy

    Claudia Kusmic, Monia Taranta, Lorena Tedeschi, Lisa Gherardini, Gualtiero Pelosi, Claudio Domenici, Maria Giovanna Trivella & Caterina Cinti

  2. Institute of Organic Synthesis and Photoreactivity (ISOF), National Research Council of Italy (CNR), Via Gobetti 101, 40129, Bologna, Italy

    Alessio Vizzoca & Caterina Cinti

  3. Institute of Applied Physics, Nello Carrara”(IFAC), National Research Council of Italy (CNR), Florence, Italy

    Ambra Giannetti, Sara Tombelli & Francesco Baldini

  4. Institute of Translational Pharmacology (IFT), National Research Council of Italy (CNR), Rome, Italy

    Settimio Grimaldi

Authors
  1. Claudia Kusmic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessio Vizzoca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monia Taranta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lorena Tedeschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lisa Gherardini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gualtiero Pelosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ambra Giannetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sara Tombelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Settimio Grimaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Francesco Baldini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Claudio Domenici
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Maria Giovanna Trivella
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Caterina Cinti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Maria Giovanna Trivella or Caterina Cinti.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

No human studies were carried out by the authors for this article. All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees.

Additional information

Communicated by Associate Editor Junjie Xiao oversaw the review of this article.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 6206 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kusmic, C., Vizzoca, A., Taranta, M. et al. Silencing Survivin: a Key Therapeutic Strategy for Cardiac Hypertrophy. J. of Cardiovasc. Trans. Res. 15, 391–407 (2022). https://doi.org/10.1007/s12265-021-10165-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-021-10165-1

Keywords

Search

Navigation