Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis
| Basic data | |
|---|---|
| OCA1. Surname awarded to the assessed person | Kyselovič |
| OCA2. Name awarded to the assessed person | Ján |
| OCA3. Degrees awarded to the assessed person | Prof. , Pharm.D., CSc. |
| OCA4. Hyperlink to the entry of the person in the Register of university staff | https://www.portalvs.sk/regzam/detail/3738 |
| OCA5. Area of assessment | study programme pharmacy (joint study programme) · I. + II. degree |
| OCA6. Category of the research/artistic/other output | scientific output |
| OCA7. Year of publication of the research/artistic/other output | 2015 |
| OCA8. ID of the record in the Central Registry of Publication Activity (CRPA) or the Central Registry of Artistic Activity (CRAA) | 648819 |
| OCA9. Hyperlink to the record in CRPA or CRAA | https://app.crepc.sk/?fn=detailBiblioForm&sid=27093A0DF76D81AC9BBE12CCAD |
| Characteristics of the output that is not registered in CRPA or CRAA | |
| OCA10. Hyperlink to the record in another publicly accessible register, catalogue of research/ artistic/other outputs | |
| OCA11. Characteristics of the output in the format of the CRPA or the CRAA bibliographic record, if the output is not available in a publicly accessible register or catalogue of outputs | Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis |
| OCA12. Type of the output (if the output is not registered in CRPA or CRAA) | article |
| OCA13. Hyperlink to the webpage where the output is available (full text, other documentation, etc.) | |
| OCA14. Characteristics of the author's contribution | member of the international team |
| OCA15. Annotation of the output with contextual information concerning the description of creative process and the content of the research/artistic/other activity, etc. | Cardiomyopathy is a common human disorder that is characterized by contractile dysfunction and cardiac remodeling. Genetic mutations and altered expression of genes encoding many signaling molecules and contractile proteins are associated with cardiomyopathy; however, how cardiomyocytes sense pathophysiological stresses in order to then modulate cardiac remodeling remains poorly understood. Here, we have described a regulator in the heart that harmonizes the progression of cardiac hypertrophy and dilation. We determined that expression of the myocyte-enriched protein cardiac ISL1-interacting protein (CIP, also known as MLIP) is reduced in patients with dilated cardiomyopathy. As CIP is highly conserved between human and mouse, we evaluated the effects of CIP deficiency on cardiac remodeling in mice. Deletion of the CIP-encoding gene accelerated progress from hypertrophy to heart failure in several cardiomyopathy models. Conversely, transgenic and AAV-mediated CIP overexpression prevented pathologic remodeling and preserved cardiac function. CIP deficiency combined with lamin A/C deletion resulted in severe dilated cardiomyopathy and cardiac dysfunction in the absence of stress. Transcriptome analyses of CIP-deficient hearts revealed that the p53- and FOXO1-mediated gene networks related to homeostasis are disturbed upon pressure overload stress. Moreover, FOXO1 overexpression suppressed stress-induced cardiomyocyte hypertrophy in CIP-deficient cardiomyocytes. Our studies identify CIP as a key regulator of cardiomyopathy that has potential as a therapeutic target to attenuate heart failure progression. |
| Other data | |
| OCA16. Annotation of the output in English | Cardiomyopathy is a common human disorder that is characterized by contractile dysfunction and cardiac remodeling. Genetic mutations and altered expression of genes encoding many signaling molecules and contractile proteins are associated with cardiomyopathy; however, how cardiomyocytes sense pathophysiological stresses in order to then modulate cardiac remodeling remains poorly understood. Here, we have described a regulator in the heart that harmonizes the progression of cardiac hypertrophy and dilation. We determined that expression of the myocyte-enriched protein cardiac ISL1-interacting protein (CIP, also known as MLIP) is reduced in patients with dilated cardiomyopathy. As CIP is highly conserved between human and mouse, we evaluated the effects of CIP deficiency on cardiac remodeling in mice. Deletion of the CIP-encoding gene accelerated progress from hypertrophy to heart failure in several cardiomyopathy models. Conversely, transgenic and AAV-mediated CIP overexpression prevented pathologic remodeling and preserved cardiac function. CIP deficiency combined with lamin A/C deletion resulted in severe dilated cardiomyopathy and cardiac dysfunction in the absence of stress. Transcriptome analyses of CIP-deficient hearts revealed that the p53- and FOXO1-mediated gene networks related to homeostasis are disturbed upon pressure overload stress. Moreover, FOXO1 overexpression suppressed stress-induced cardiomyocyte hypertrophy in CIP-deficient cardiomyocytes. Our studies identify CIP as a key regulator of cardiomyopathy that has potential as a therapeutic target to attenuate heart failure progression. |
| OCA17. List of maximum 5 most significant citations corresponding to the output | 2021: Liu, N. - Kataoka, M. - Wang, Y. - Pu, L. - Dong, X. - Fu, X. - Zhang, F. - Gao, F. - Liang, T. - Pei, J. - Xiao, C. - Qiu, Q. - Hong, T. - Chen, Q. - Zhao, J. - Zhu, L. - He, J. - Hu, X. - Nie, Y. - Zhu, W. - Yu, H. - Cowan, D.B.- Hu, X. - Wang, J. - Wang, D.-Z. - Chen, J.: LncRNA LncHrt preserves cardiac metabolic homeostasis and heart function by modulating the LKB1-AMPK signaling pathway. In: Basic Research in Cardiology, vol. 116, no.1, 2021, art. no. 48 -- SCI ; SCOPUS 2022: Bermejo-Guerrero, L. - Arteche-López, A. - De Fuenmayor Fernández De La Hoz, C. - Hernández-Laín, A. - Martín, M.A. - Domínguez-González, C.: A novel MLIP truncating variant in an 80-year-old patient with late-onset progressiveweakness. In: Brain, vol. 145, no. 10, 2022, s. E99-E102 -- SCI ; SCOPUS 2023: Meng, Z. - Zhang, Z. - Zhao, J. - Liu, C. - Yao, P. - Zhang, L. - Xie, D. - Lau, W.B. - Tsukuda, J. - Christopher, T.A. - Lopez, B. - Zhu, D. - Liu, D. - Zhang, J.R. - Gao, E. - Ischiropoulos, H. - Koch, W. - Ma, X. - Wang, Y.: Nitrative Modification of Caveolin-3: A Novel Mechanism of Cardiac Insulin Resistance and a Potential Therapeutic Target Against Ischemic Heart Failure in Prediabetic Animals. In: Circulation, vol. 147, no. 15, 2023, s. 1162- 1179 -- SCI ; SCOPUS 2023: Zhu, X. - Li, Q. - George, V. - Spanoudis, C. - Gilkes, C. - Shrestha, N. - Liu, B. - Kong, L. - You, L. - Echeverri, C. - Li, L. - Wang, Z. - Chaturvedi, P. - Muniz, G.J. - Egan, J.O. - Rhode, P.R. - Wong, H.C.: Frontiers inImmunology, vol. 14, 2023, art. no. 1114802 -- SCI ; SCOPUS 2024: Wu, Y. - Zhu, X. - Jiang, W. - Li, J. - Li, H. - Zhang, K. - Yang, Y. - Qu, S. - Guan, X. - Bai, Y. - Guo, H. - Dai, L.: LMNA-related muscular dystrophy involving myoblast proliferation and apptosis through the FOXO1/GADD45Apathway. In: Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1870, no. 2, 2024, art. no. 166943 -- SCOPUS |
| OCA18. Characteristics of the output's impact on socio-economic practice | contribution of new knowledge to the issue |
| OCA19. Characteristics of the output and related activities' impact on the educational process | research in the field |