E009 – Cellular and Molecular Cardiology

Objectives

1.- Contribute to the development of future “precision” therapies for heart failure by studying the specific pathophysiological alterations that characterize the different phenotypes of patients with this pathology. Heart failure represents an important socio-sanitary problem due to its high prevalence, high hospitalization and mortality rates, and significant health costs. It comprises a heterogeneous group of syndromes with complex and not fully known pathophysiological mechanisms, and different clinical presentation and response to treatment. The specific objectives of our work include the analysis of the metabolic profiles of the cardiac tissue of patients with different phenotypes of heart failure, the identification of new metabolic and inflammatory pathophysiological mediators in these patients, and the in vivo and in vitro study of alterations in the metabolic pathways that characterize the different phenotypes of this disease, in order to help identify and validate new, more specific and adapted therapeutic targets.
2.-Investigate new effects at the cardiomyocyte and cardiometabolic level of the most promising drugs for the treatment of heart failure at present (inhibitors of sodium-glucose cotransporter type 2, stimulators of soluble guanylate cyclase and dual inhibitors of angiotensin II receptor and neprilysin).

Lines of research

1.-Study of mitochondrial dysfunction and changes in cardiac metabolism in heart failure.
2.-Possible new effects of the neprilysin and valsartan inhibitor LCZ696 on the regulation of viability and cardiomyocyte metabolism.
3.-Analysis of the effects of the SGLT2 inhibitor empagliflozin on the regulation of energy metabolism in cardiac, hepatic and visceral adipose tissue.

• Aragón-Herrera A, Feijóo-Bandín S, Moraña-Fernández S, Anido-Varela L, Roselló-Lletí E, Portolés M, Tarazón E, Lage R, Moscoso I, Barral L, Bani D, Bigazzi M, Gualillo O, González-Juanatey JR, Lago F. Relaxin has beneficial effects on liver lipidome and metabolic enzymes. FASEB J. 2021 Jul;35(7):e21737. doi: 10.1096/fj.202002620RR. PMID: 34143495.
• Feijóo-Bandín S, Aragón-Herrera A, Moraña-Fernández S, Anido-Varela L, Tarazón E, Roselló-Lletí E, Portolés M, Moscoso I, Gualillo O, González-Juanatey JR, Lago F. Adipokines and Inflammation: Focus on Cardiovascular Diseases. Int J Mol Sci. 2020 Oct 18;21(20):7711. doi: 10.3390/ijms21207711. PMID: 33081064; PMCID: PMC7589803.
• Pettinelli N, Rodríguez-Llamazares S, Bouza R, Barral L, Feijoo-Bandín S, Lago F. Carrageenan-based physically crosslinked injectable hydrogel for wound healing and tissue repairing applications. Int J Pharm. 2020 Nov 15;589:119828. doi: 10.1016/j.ijpharm.2020.119828. Epub 2020 Aug 29. PMID: 32871220.
• Pettinelli N, Rodríguez-Llamazares S, Farrag Y, Bouza R, Barral L, Feijoo- Bandín S, Lago F. Poly(hydroxybutyrate-co-hydroxyvalerate) microparticles embedded in κ-carrageenan/locust bean gum hydrogel as a dual drug delivery carrier. Int J Biol Macromol. 2020 Mar 1;146:110-118. doi: 10.1016/j.ijbiomac.2019.12.193. Epub 2019 Dec 24. PMID: 31881300.
• Aragón-Herrera A, Feijóo-Bandín S, Otero Santiago M, Barral L, Campos-Toimil M, Gil-Longo J, Costa Pereira TM, García-Caballero T, Rodríguez-Segade S, Rodríguez J, Tarazón E, Roselló-letí E, Portolés M, Gualillo O, González- Juanatey JR, Lago F. Empagliflozin reduces the levels of CD36 and cardiotoxic lipids while improving autophagy in the hearts of Zucker diabetic fatty rats. Biochem Pharmacol. 2019 Dec;170:113677. doi: 10.1016/j.bcp.2019.113677. Epub 2019 Oct 21. PMID: 31647926.
• Álvarez-Álvarez L, Barral L, Bouza R, Farrag Y, Otero-Espinar F, Feijóo- Bandín S, Lago F. Hydrocortisone loaded poly-(3-hydroxybutyrate- co-3-hydroxyvalerate) nanoparticles for topical ophthalmic administration: Preparation, characterization and evaluation of ophthalmic toxicity. Int J Pharm. 2019 Sep 10;5683A118519. doi: 10.1016/j.ijpharm.2019.118519. Epub 2019 Jul 13. PMID: 31310791.
• Aragón-Herrera A, Feijóo-Bandín S, Abella V, Álvarez L, Roselló-Lletí E, Portolés M, Tarazón E, Bigazzi M, Bani D, Gualillo O, González-Juanatey JR, Lago F. Serelaxin (recombinant human relaxin-2) treatment affects the endogenous synthesis of long chain poly-unsaturated fatty acids and induces substantial alterations of lipidome and metabolome profiles in rat cardiac tissue. Pharmacol Res. 2019 Jun;144:51-65. doi: 10.1016/j.phrs.2019.04.009. Epub 2019 Apr 5. PMID: 30954631.
• Pettinelli N, Rodríguez-Llamazares S, Abella V, Barral L, Bouza R, Farrag Y, Lago F. Entrapment of chitosan, pectin or κ-carrageenan within methacrylate based hydrogels: Effect on swelling and mechanical properties. Mater Sci Eng C Mater Biol Appl. 2019 Mar;96:583-590. doi: 10.1016/j.msec.2018.11.071. Epub 2018 Nov 29. PMID: 30606569.