RT Journal Article
T1 The Impact of Melatonin Supplementation and NLRP3 Inflammasome Deletion on Age-Accompanied Cardiac Damage.
A1 Sayed, Ramy K A
A1 Fernández-Ortiz, Marisol
A1 Rahim, Ibtissem
A1 Fernández-Martínez, José
A1 Aranda-Martínez, Paula
A1 Rusanova, Iryna
A1 Martínez-Ruiz, Laura
A1 Alsaadawy, Reem M
A1 Escames, Germaine
A1 Acuña-Castroviejo, Darío
K1 CSA
K1 NLRP3 inflammasome
K1 autophagosome
K1 cardiomyocytes
K1 melatonin
K1 mitochondria
K1 sarcopenia
K1 ultrastructure
K1 β-MHC
AB To investigate the role of NLRP3 inflammasome in cardiac aging, we evaluate here morphological and ultrastructural age-related changes of cardiac muscles fibers in wild-type and NLRP3-knockout mice, as well as studying the beneficial effect of melatonin therapy. The results clarified the beginning of the cardiac sarcopenia at the age of 12 months, with hypertrophy of cardiac myocytes, increased expression of β-MHC, appearance of small necrotic fibers, decline of cadiomyocyte number, destruction of mitochondrial cristae, appearance of small-sized residual bodies, and increased apoptotic nuclei ratio. These changes were progressed in the cardiac myocytes of 24 old mice, accompanied by excessive collagen deposition, higher expressions of IL-1α, IL-6, and TNFα, complete mitochondrial vacuolation and damage, myofibrils disorganization, multivesicular bodies formation, and nuclear fragmentation. Interestingly, cardiac myocytes of NLRP3-/- mice showed less detectable age-related changes compared with WT mice. Oral melatonin therapy preserved the normal cardiomyocytes structure, restored cardiomyocytes number, and reduced β-MHC expression of cardiac hypertrophy. In addition, melatonin recovered mitochondrial architecture, reduced apoptosis and multivesicular bodies' formation, and decreased expressions of β-MHC, IL-1α, and IL-6. Fewer cardiac sarcopenic changes and highly remarkable protective effects of melatonin treatment detected in aged cardiomyocytes of NLRP3-/- mice compared with aged WT animals, confirming implication of the NLRP3 inflammasome in cardiac aging. Thus, NLRP3 suppression and melatonin therapy may be therapeutic approaches for age-related cardiac sarcopenia.
SN 2076-3921
YR 2021
FD 2021-08-10
LK https://hdl.handle.net/10668/26095
UL https://hdl.handle.net/10668/26095
LA en
DS RISalud
RD Apr 7, 2025