Developmental and sex differences in cardiac tolerance to ischemia–reperfusion injury: the role of mitochondria
Age and sex play an essential role in the cardiac tolerance to ischemia–reperfusion injury: cardiac resistance significantly decreases during postnatal maturation and the female heart is more tolerant than the male myocardium. It is widely accepted that mitochondrial dysfunction, and particularly mi...
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Published in | Canadian journal of physiology and pharmacology Vol. 97; no. 9; pp. 808 - 814 |
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Main Authors | , , , , , , |
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01.09.2019
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Abstract | Age and sex play an essential role in the cardiac tolerance to ischemia–reperfusion injury: cardiac resistance significantly decreases during postnatal maturation and the female heart is more tolerant than the male myocardium. It is widely accepted that mitochondrial dysfunction, and particularly mitochondrial permeability transition pore (MPTP) opening, plays a major role in determining the extent of cardiac ischemia–reperfusion injury. We have observed that the MPTP sensitivity to the calcium load differs in mitochondria isolated from neonatal and adult myocardium, as well as from adult male and female hearts. Neonatal and female mitochondria are more resistant both in the extent and in the rate of mitochondrial swelling induced by high calcium concentration. Our data further suggest that age- and sex-dependent specificity of the MPTP is not the result of different amounts of ATP synthase and cyclophilin D: neonatal and adult hearts, similarly as the male and female hearts, contain comparable amounts of MPTP and its regulatory protein cyclophilin D. We can speculate that the lower sensitivity of MPTP to the calcium-induced swelling may be related to the higher ischemic tolerance of both neonatal and female myocardium. |
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AbstractList | Age and sex play an essential role in the cardiac tolerance to ischemia–reperfusion injury: cardiac resistance significantly decreases during postnatal maturation and the female heart is more tolerant than the male myocardium. It is widely accepted that mitochondrial dysfunction, and particularly mitochondrial permeability transition pore (MPTP) opening, plays a major role in determining the extent of cardiac ischemia–reperfusion injury. We have observed that the MPTP sensitivity to the calcium load differs in mitochondria isolated from neonatal and adult myocardium, as well as from adult male and female hearts. Neonatal and female mitochondria are more resistant both in the extent and in the rate of mitochondrial swelling induced by high calcium concentration. Our data further suggest that age- and sex-dependent specificity of the MPTP is not the result of different amounts of ATP synthase and cyclophilin D: neonatal and adult hearts, similarly as the male and female hearts, contain comparable amounts of MPTP and its regulatory protein cyclophilin D. We can speculate that the lower sensitivity of MPTP to the calcium-induced swelling may be related to the higher ischemic tolerance of both neonatal and female myocardium. Age and sex play an essential role in the cardiac tolerance to ischemia–reperfusion injury: cardiac resistance significantly decreases during postnatal maturation and the female heart is more tolerant than the male myocardium. It is widely accepted that mitochondrial dysfunction, and particularly mitochondrial permeability transition pore (MPTP) opening, plays a major role in determining the extent of cardiac ischemia–reperfusion injury. We have observed that the MPTP sensitivity to the calcium load differs in mitochondria isolated from neonatal and adult myocardium, as well as from adult male and female hearts. Neonatal and female mitochondria are more resistant both in the extent and in the rate of mitochondrial swelling induced by high calcium concentration. Our data further suggest that age- and sex-dependent specificity of the MPTP is not the result of different amounts of ATP synthase and cyclophilin D: neonatal and adult hearts, similarly as the male and female hearts, contain comparable amounts of MPTP and its regulatory protein cyclophilin D. We can speculate that the lower sensitivity of MPTP to the calcium-induced swelling may be related to the higher ischemic tolerance of both neonatal and female myocardium.L’âge et le sexe jouent un rôle essentiel dans la tolérance du cœur aux lésions d’ischémie–reperfusion : la résistance du cœur diminue nettement pendant le mûrissement postnatal, et le cœur femelle est plus tolérant que le myocarde mâle. Il est largement accepté que le dysfonctionnement myocardique, et plus particulièrement l’ouverture des pores de transition de perméabilité mitochondriale (PTPM), joue un rôle majeur dans la détermination de l’étendue des lésions d’ischémie–reperfusion dans le cœur. Nous avons observé que la sensibilité des PTPM à la charge en calcium des mitochondries isolées de myocarde néonatal est différente de celle du myocarde adulte, ainsi qu’entre les cœurs mâles et femelles. Les mitochondries néonatales et femelles sont plus résistantes quant à l’ampleur et à la vitesse du gonflement mitochondrial provoqué par des concentrations élevées de calcium. Nos données laissent aussi entendre que la spécificité des PTPM en fonction de l’âge et du sexe n’est pas le résultat de différences quant aux quantités d’ATP synthase et de cyclophiline D : les cœurs néonataux comme adultes, de manière similaire aux cœurs mâles et femelles, contiennent des quantités comparables de PTPM et de cyclophiline D, leur protéine régulatrice. Nous sommes en mesure de spéculer que la plus faible sensibilité des PTPM au gonflement provoqué par le calcium pourrait être liée à la plus grande tolérance à l’ischémie du myocarde néonatal comme du myocarde femelle. [Traduit par la Rédaction] |
Author | Houstek, J. Drahota, Z. Kolar, F. Milerova, M. Hlavackova, M. Ostadal, B. Ostadalova, I. |
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SubjectTerms | Age ATP ATP synthase Calcium Gender differences Heart Ischemia Membrane permeability Mitochondria Mitochondrial permeability transition pore Myocardium Neonates Newborn babies Pharmacology Physiology Reperfusion Sensitivity Sex differences |
Title | Developmental and sex differences in cardiac tolerance to ischemia–reperfusion injury: the role of mitochondria |
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