Academic Journal
Confirmation of the Cardioprotective Effect of MitoGamide in the Diabetic Heart.
| Τίτλος: | Confirmation of the Cardioprotective Effect of MitoGamide in the Diabetic Heart. |
|---|---|
| Συγγραφείς: | Park M; Department of Medicine, University of Cambridge, Cambridge, UK., Nishimura T; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.; Takeda Pharmaceutical Ltd, Tokyo, Japan., Baeza-Garza CD; WestCHEM School of Chemistry, University of Glasgow, Glasgow, UK., Caldwell ST; WestCHEM School of Chemistry, University of Glasgow, Glasgow, UK., Pun PBL; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK., Prag HA; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK., Young T; Department of Medicine, University of Cambridge, Cambridge, UK., Sauchanka O; Department of Medicine, University of Cambridge, Cambridge, UK., Logan A; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK., Forkink M; Department of Medicine, University of Cambridge, Cambridge, UK., Gruszczyk AV; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK., Prime TA; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK., Arndt S; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK., Naudi A; Department Of Experimental Medicine, University of Lleida, Lleida Institute for Biomedical Research, Lleida, Spain., Pamplona R; Department Of Experimental Medicine, University of Lleida, Lleida Institute for Biomedical Research, Lleida, Spain., Coughlan MT; Department of Diabetes, Monash University, Melbourne, Australia., Tate M; Department of Diabetes, Monash University, Melbourne, Australia.; Baker Heart and Diabetes Institute, Melbourne, Australia., Ritchie RH; Department of Diabetes, Monash University, Melbourne, Australia.; Baker Heart and Diabetes Institute, Melbourne, Australia., Caicci F; Department of Biology, University of Padova, Padua, Italy., Kaludercic N; Neuroscience Institute, National Research Council of Italy (CNR), Pisa, Italy., Di Lisa F; Department of Biomedical Sciences, University of Padova, Padua, Italy., Smith RAJ; Department of Chemistry, University of Otago, Otago, New Zealand., Hartley RC; WestCHEM School of Chemistry, University of Glasgow, Glasgow, UK., Murphy MP; Department of Medicine, University of Cambridge, Cambridge, UK.; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK., Krieg T; Department of Medicine, University of Cambridge, Cambridge, UK. tk382@medschl.cam.ac.uk. |
| Πηγή: | Cardiovascular drugs and therapy [Cardiovasc Drugs Ther] 2020 Dec; Vol. 34 (6), pp. 823-834. Date of Electronic Publication: 2020 Sep 26. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Kluwer Academic For The International Society For Cardiovascular Pharmacotherapy Country of Publication: United States NLM ID: 8712220 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7241 (Electronic) Linking ISSN: 09203206 NLM ISO Abbreviation: Cardiovasc Drugs Ther Subsets: MEDLINE |
| Imprint Name(s): | Publication: Norwell Ma : Kluwer Academic For The International Society For Cardiovascular Pharmacotherapy Original Publication: [Norwell, MA] : Martinus Nijhoff Pub., [c1987- |
| Ιατρικοί όροι (MeSH): | Benzamides/*pharmacology , Cardiovascular Agents/*pharmacology , Diabetic Cardiomyopathies/*prevention & control , Heart Failure/*prevention & control , Stroke Volume/*drug effects , Ventricular Dysfunction, Left/*prevention & control , Ventricular Function, Left/*drug effects, Diabetic Cardiomyopathies/metabolism ; Diabetic Cardiomyopathies/physiopathology ; Glycation End Products, Advanced/metabolism ; Heart Failure/metabolism ; Heart Failure/physiopathology ; Mitochondria, Heart/drug effects ; Mitochondria, Heart/metabolism ; Ventricular Dysfunction, Left/metabolism ; Ventricular Dysfunction, Left/physiopathology ; Animals ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Mice, Mutant Strains |
| Περίληψη: | Purpose: HFpEF (heart failure with preserved ejection fraction) is a major consequence of diabetic cardiomyopathy with no effective treatments. Here, we have characterized Akita mice as a preclinical model of HFpEF and used it to confirm the therapeutic efficacy of the mitochondria-targeted dicarbonyl scavenger, MitoGamide. Methods and Results: A longitudinal echocardiographic analysis confirmed that Akita mice develop diastolic dysfunction with reduced E peak velocity, E/A ratio and extended isovolumetric relaxation time (IVRT), while the systolic function remains comparable with wild-type mice. The myocardium of Akita mice had a decreased ATP/ADP ratio, elevated mitochondrial oxidative stress and increased organelle density, compared with that of wild-type mice. MitoGamide, a mitochondria-targeted 1,2-dicarbonyl scavenger, exhibited good stability in vivo, uptake into cells and mitochondria and reactivity with dicarbonyls. Treatment of Akita mice with MitoGamide for 12 weeks significantly improved the E/A ratio compared with the vehicle-treated group. Conclusion: Our work confirms that the Akita mouse model of diabetes replicates key clinical features of diabetic HFpEF, including cardiac and mitochondrial dysfunction. Furthermore, in this independent study, MitoGamide treatment improved diastolic function in Akita mice. |
| References: | J Lipid Res. 2011 Aug;52(8):1483-93. (PMID: 21606463) Basic Res Cardiol. 2018 Aug 17;113(5):39. (PMID: 30120595) J Am Coll Cardiol. 2019 Feb 12;73(5):602-611. (PMID: 30732715) Aging Cell. 2014 Oct;13(5):828-37. (PMID: 25052291) Eur J Heart Fail. 2018 Sep;20(9):1303-1311. (PMID: 29877602) Antioxid Redox Signal. 2019 Jan 20;30(3):354-374. (PMID: 29160087) Circ Res. 2016 Jun 24;119(1):159-76. (PMID: 27340274) Am J Physiol Heart Circ Physiol. 2009 Dec;297(6):H2096-108. (PMID: 19801494) Drugs. 2010 Dec 3;70(17):2229-45. (PMID: 21080740) J Am Coll Cardiol. 2013 Jul 23;62(4):263-71. (PMID: 23684677) J Biol Chem. 2003 Sep 12;278(37):34757-63. (PMID: 12815061) Diabetes. 2015 Jan;64(1):257-65. (PMID: 24848072) Diabetologia. 2005 Aug;48(8):1590-603. (PMID: 15988580) Front Endocrinol (Lausanne). 2017 Jul 17;8:160. (PMID: 28769873) Am J Physiol Renal Physiol. 2010 Mar;298(3):F788-95. (PMID: 20042456) Amino Acids. 2013 Feb;44(2):361-71. (PMID: 22722543) Diabetes. 2008 Nov;57(11):2924-32. (PMID: 18678617) Aging Cell. 2008 Mar;7(2):260-9. (PMID: 18221415) Biochim Biophys Acta. 2014 Feb;1840(2):923-30. (PMID: 23726990) Semin Cell Dev Biol. 2011 May;22(3):309-17. (PMID: 21335095) Free Radic Biol Med. 2014 Feb;67:437-50. (PMID: 24316194) Diabetes. 2015 Jan;64(1):266-78. (PMID: 25187362) Nature. 2001 Dec 13;414(6865):813-20. (PMID: 11742414) Clin Sci (Lond). 1994 Jul;87(1):21-9. (PMID: 8062515) Biochem Pharmacol. 2009 Jun 1;77(11):1709-16. (PMID: 19428325) Antioxid Redox Signal. 2011 Dec 15;15(12):3021-38. (PMID: 21395490) Nat Rev Cardiol. 2012 Mar 27;9(6):347-59. (PMID: 22450126) Diabetologia. 2012 Sep;55(9):2513-21. (PMID: 22572804) Cardiovasc Drugs Ther. 2019 Dec;33(6):669-674. (PMID: 31654171) Diabetes. 2009 Sep;58(9):1986-97. (PMID: 19542201) |
| Grant Information: | 110158/Z/15/Z United Kingdom WT_ Wellcome Trust; MC_U105663142 United Kingdom MRC_ Medical Research Council; PG/15/84/31670 United Kingdom BHF_ British Heart Foundation |
| Contributed Indexing: | Keywords: Advanced glycation endproducts (AGE); Akita mice; Diabetes; Heart failure with preserved ejection fraction (HFpEF); Mitochondria |
| Substance Nomenclature: | 0 (Benzamides) 0 (Cardiovascular Agents) 0 (Glycation End Products, Advanced) 0 (MitoGamide) |
| Entry Date(s): | Date Created: 20200926 Date Completed: 20210608 Latest Revision: 20250530 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7674384 |
| DOI: | 10.1007/s10557-020-07086-7 |
| PMID: | 32979176 |
| Βάση Δεδομένων: | MEDLINE |
καταχωρήστε σχόλιο πρώτοι!