Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy.

Autor: Donato M; Department of Pathology, Faculty of Medicine, Institute of Cardiovascular Pathophysiology, University of Buenos Aires, J. E. Uriburu 950, 2nd floor, C1114AAD, Buenos Aires, Argentina., Buchholz B; Department of Pathology, Faculty of Medicine, Institute of Cardiovascular Pathophysiology, University of Buenos Aires, J. E. Uriburu 950, 2nd floor, C1114AAD, Buenos Aires, Argentina., Morales C; Department of Pathology, Faculty of Medicine, Institute of Cardiovascular Pathophysiology, University of Buenos Aires, J. E. Uriburu 950, 2nd floor, C1114AAD, Buenos Aires, Argentina., Valdez L; School of Pharmacy and Biochemistry, Institute of Biochemistry and Molecular Medicine, University of Buenos Aires-CONICET, Buenos Aires, Argentina., Zaobornyj T; School of Pharmacy and Biochemistry, Institute of Biochemistry and Molecular Medicine, University of Buenos Aires-CONICET, Buenos Aires, Argentina., Baratta S; Institute of Cardiology and Cardiovascular Therapeutic, Austral Hospital, Buenos Aires, Argentina., Paez DT; Department of Pathology, Faculty of Medicine, Institute of Cardiovascular Pathophysiology, University of Buenos Aires, J. E. Uriburu 950, 2nd floor, C1114AAD, Buenos Aires, Argentina., Matoso M; Department of Pathology, Faculty of Medicine, Institute of Cardiovascular Pathophysiology, University of Buenos Aires, J. E. Uriburu 950, 2nd floor, C1114AAD, Buenos Aires, Argentina., Vaccarino G; Institute of Cardiology and Cardiovascular Therapeutic, Austral Hospital, Buenos Aires, Argentina., Chejtman D; Institute of Cardiology and Cardiovascular Therapeutic, Austral Hospital, Buenos Aires, Argentina., Agüero O; Institute of Cardiology and Cardiovascular Therapeutic, Austral Hospital, Buenos Aires, Argentina., Telayna J; Institute of Cardiology and Cardiovascular Therapeutic, Austral Hospital, Buenos Aires, Argentina., Navia J; Institute of Cardiology and Cardiovascular Therapeutic, Austral Hospital, Buenos Aires, Argentina., Hita A; Institute of Cardiology and Cardiovascular Therapeutic, Austral Hospital, Buenos Aires, Argentina., Boveris A; School of Pharmacy and Biochemistry, Institute of Biochemistry and Molecular Medicine, University of Buenos Aires-CONICET, Buenos Aires, Argentina., Gelpi RJ; Department of Pathology, Faculty of Medicine, Institute of Cardiovascular Pathophysiology, University of Buenos Aires, J. E. Uriburu 950, 2nd floor, C1114AAD, Buenos Aires, Argentina. rgelpi@fmed.uba.ar.
Jazyk: angličtina
Zdroj: Molecular and cellular biochemistry [Mol Cell Biochem] 2017 Aug; Vol. 432 (1-2), pp. 169-178. Date of Electronic Publication: 2017 Mar 18.
DOI: 10.1007/s11010-017-3007-z
Abstrakt: Transition from compensated to decompensated left ventricular hypertrophy (LVH) is accompanied by functional and structural changes. Here, the aim was to evaluate dystrophin expression in murine models and human subjects with LVH by transverse aortic constriction (TAC) and aortic stenosis (AS), respectively. We determined whether doxycycline (Doxy) prevented dystrophin expression and myocardial stiffness in mice. Additionally, ventricular function recovery was evaluated in patients 1 year after surgery. Mice were subjected to TAC and monitored for 3 weeks. A second group received Doxy treatment after TAC. Patients with AS were stratified by normal left ventricular end-diastolic wall stress (LVEDWS) and high LVEDWS, and groups were compared. In mice, LVH decreased inotropism and increased myocardial stiffness associated with a dystrophin breakdown and a decreased mitochondrial O 2 uptake (MitoMVO 2 ). These alterations were attenuated by Doxy. Patients with high LVEDWS showed similar results to those observed in mice. A correlation between dystrophin and myocardial stiffness was observed in both mice and humans. Systolic function at 1 year post-surgery was only recovered in the normal-LVEDWS group. In summary, mice and humans present diastolic dysfunction associated with dystrophin degradation. The recovery of ventricular function was observed only in patients with normal LVEDWS and without dystrophin degradation. In mice, Doxy improved MitoMVO 2 . Based on our results it is concluded that the LVH with high LVEDWS is associated to a degradation of dystrophin and increase of myocardial stiffness. At least in a murine model these alterations were attenuated after the administration of a matrix metalloprotease inhibitor.
Databáze: MEDLINE
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