Evidence that tirzepatide protects against diabetes-related cardiac damages
Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-024-02203-4 |
| _version_ | 1797233835249762304 |
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| author | Fatemeh Taktaz Lucia Scisciola Rosaria Anna Fontanella Ada Pesapane Puja Ghosh Martina Franzese Giovanni Tortorella Armando Puocci Eduardo Sommella Giuseppe Signoriello Fabiola Olivieri Michelangela Barbieri Giuseppe Paolisso |
| author_facet | Fatemeh Taktaz Lucia Scisciola Rosaria Anna Fontanella Ada Pesapane Puja Ghosh Martina Franzese Giovanni Tortorella Armando Puocci Eduardo Sommella Giuseppe Signoriello Fabiola Olivieri Michelangela Barbieri Giuseppe Paolisso |
| author_sort | Fatemeh Taktaz |
| collection | DOAJ |
| description | Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. Methods A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. Results Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40–0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure. Conclusion Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT. Graphical Abstract |
| first_indexed | 2024-04-24T16:22:29Z |
| format | Article |
| id | doaj.art-84a24c088642420db1de6f8e5cb9fb78 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-24T16:22:29Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-84a24c088642420db1de6f8e5cb9fb782024-03-31T11:10:01ZengBMCCardiovascular Diabetology1475-28402024-03-0123111510.1186/s12933-024-02203-4Evidence that tirzepatide protects against diabetes-related cardiac damagesFatemeh Taktaz0Lucia Scisciola1Rosaria Anna Fontanella2Ada Pesapane3Puja Ghosh4Martina Franzese5Giovanni Tortorella6Armando Puocci7Eduardo Sommella8Giuseppe Signoriello9Fabiola Olivieri10Michelangela Barbieri11Giuseppe Paolisso12Department of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Department of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Department of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Department of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Department of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Department of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Department of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Department of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Department of Pharmacy, University of SalernoDepartment of Mental Health and Public Medicine, Section of Statistic, University of CampaniaDepartment of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle MarcheDepartment of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Department of Advanced Medical and Surgical Sciences, University of Campania ‘‘Luigi Vanvitelli’’Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. Methods A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. Results Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40–0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure. Conclusion Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT. Graphical Abstracthttps://doi.org/10.1186/s12933-024-02203-4TirzepatideHeart failureAC16 cell lineHigh glucoseGIP receptorGLP-1 receptor. |
| spellingShingle | Fatemeh Taktaz Lucia Scisciola Rosaria Anna Fontanella Ada Pesapane Puja Ghosh Martina Franzese Giovanni Tortorella Armando Puocci Eduardo Sommella Giuseppe Signoriello Fabiola Olivieri Michelangela Barbieri Giuseppe Paolisso Evidence that tirzepatide protects against diabetes-related cardiac damages Cardiovascular Diabetology Tirzepatide Heart failure AC16 cell line High glucose GIP receptor GLP-1 receptor. |
| title | Evidence that tirzepatide protects against diabetes-related cardiac damages |
| title_full | Evidence that tirzepatide protects against diabetes-related cardiac damages |
| title_fullStr | Evidence that tirzepatide protects against diabetes-related cardiac damages |
| title_full_unstemmed | Evidence that tirzepatide protects against diabetes-related cardiac damages |
| title_short | Evidence that tirzepatide protects against diabetes-related cardiac damages |
| title_sort | evidence that tirzepatide protects against diabetes related cardiac damages |
| topic | Tirzepatide Heart failure AC16 cell line High glucose GIP receptor GLP-1 receptor. |
| url | https://doi.org/10.1186/s12933-024-02203-4 |
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