Dataset Information

Age associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients.

ABSTRACT:

Background

Aging is a complex physiological phenomenon, intricately associated with cardiovascular pathologies, where platelets play a central pathophysiological role. Although antiplatelets are commonly employed to prevent and treat major adverse cardiovascular events, aging associated intraplatelet changes remain largely unexplored.

Methods

Platelets were studied in high cardiovascular risk patients (aged 40-100?years) comparing them to younger healthy subjects. This was followed by cross sectional and longitudinal mice studies. Flow cytometry, biochemical and molecular assays were used to study platelets comprehensively.

Findings

CVD Patients were categorized in the age groups 40-59, 60-79, and 80-100?years. Progressive decline in platelet health was observed in the 40-79?years age cohort, marked by increase in oxidative stress, hyperactivation and apoptotic markers. Paradoxically, this was reversed in patients aged above 79?years and the improved platelet phenotype was associated with lower oxidative damage. The platelets from the very old (80-100?year) group were found to be preloaded with increased antioxidants, which also contributed to higher resistance against induced redox insults. Cross sectional mouse studies excluded the effect of comorbidities and medications. Longitudinal mouse studies implicate an adaptive increase in antioxidant levels as the mechanism.

Interpretation

We report a novel age associated, non-linear redox regulation in platelets in both humans and mice. In advanced age, there occurs an adaptive increase in platelet antioxidants, reducing the intracellular ROS and leading to a healthier platelet phenotype. Clinically, our results advocate the use of less aggressive antiplatelet therapies for CVD in the elderly population. FUND: Study funded by NIH-NHLBI, RO1-HL122815 and RO1-HL115247.

SUBMITTER: Jain K

PROVIDER: S-EPMC6604369 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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