Key result
Aging impairs Ca2+-handling proteins and LV function without increasing susceptibility to ischemia-reperfusion injury.
Why the study?
During aging, heart structure and function gradually deteriorate, increasing susceptibility to ischemia-reperfusion, but the age-dependent role of Ca2+-handling proteins requires clarification.
Absolute Event Rate: 843.7% vs 1506.4%
p-value: p=<0.001
Aging decreases the abundance and function of Ca2+-handling proteins in the heart, but does not increase susceptibility to ischemia-reperfusion-induced damage.
During aging, heart structure and function gradually deteriorate, which subsequently increases susceptibility to ischemia–reperfusion (IR). Maintenance of Ca2+ homeostasis is critical for cardiac contractility. We used Langendorff’s model to monitor the susceptibility of aging (6-, 15-, and 24-month-old) hearts to IR, with a specific focus on Ca2+-handling proteins. IR, but not aging itself, triggered left ventricular changes when the maximum rate of pressure development decreased in 24-month-olds, and the maximum rate of relaxation was most affected in 6-month-old hearts. Aging caused a deprivation of Ca2+-ATPase (SERCA2a), Na+/Ca2+ exchanger, mitochondrial Ca2+ uniporter, and ryanodine receptor contents. IR-induced damage to ryanodine receptor stimulates Ca2+ leakage in 6-month-old hearts and elevated phospholamban (PLN)-to-SERCA2a ratio can slow down Ca2+ reuptake seen at 2–5 μM Ca2+. Total and monomeric PLN mirrored the response of overexpressed SERCA2a after IR in 24-month-old hearts, resulting in stable Ca2+-ATPase activity. Upregulated PLN accelerated inhibition of Ca2+-ATPase activity at low free Ca2+ in 15-month-old after IR, and reduced SERCA2a content subsequently impairs the Ca2+-sequestering capacity. In conclusion, our study suggests that aging is associated with a significant decrease in the abundance and function of Ca2+-handling proteins. However, the IR-induced damage was not increased during aging.
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Bencúrová et al. (2023) studied Myocardial ischemia-reperfusion injury (n=45). Ischemia-reperfusion vs. Control-perfused hearts was evaluated on Maximum rate of pressure development (LV +dP/dt) in 24-month-old hearts (p=<0.001). Aging is associated with a significant decrease in the abundance and function of Ca2+-handling proteins, though overall susceptibility to ischemia-reperfusion-induced damage did not increase with age.
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