The Impact of Melatonin Supplementation and NLRP3 Inflammasome Deletion on Age-Accompanied Cardiac Damage
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AuteurSayed, Ramy K. A.; Fernández Ortiz, Marisol; Fernández Martínez, José; Aranda Martínez, Paula; Rusanova Rusanova, Iryna; Martínez Ruiz, Laura; Escames Rosa, Germaine; Acuña Castroviejo, Darío
Sayed, R.K.A... [et al.]. The Impact of Melatonin Supplementation and NLRP3 Inflammasome Deletion on Age-Accompanied Cardiac Damage. Antioxidants 2021, 10, 1269. [https://doi.org/10.3390/antiox10081269]
PatrocinadorInstituto de Salud Carlos III (European Regional Development Fund/European Social Fund "Investing in your future") PI13-981 PI16-00519 PI19-01372 CB/10/00238; Junta de Andalucia CTS-101; Sohag University; German Research Foundation (DFG)
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 beta-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-1 alpha, IL-6, and TNF alpha, 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 beta-MHC expression of cardiac hypertrophy. In addition, melatonin recovered mitochondrial architecture, reduced apoptosis and multivesicular bodies' formation, and decreased expressions of beta-MHC, IL-1 alpha, 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.