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

ACCESS DATA

Publications

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

Jain Kanika K Tyagi Tarun T Patell Kanchi K Xie Yi Y Kadado Anis John AJ Lee Seung Hee SH Yarovinsky Timur T Du Jing J Hwang Janice J Martin Kathleen A KA Testani Jeffrey J Ionescu Costin N CN Hwa John J

EBioMedicine 20190524

<h4>Background</h4>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.<h4>Methods</h4>Platelets were studied in high cardiovascular risk patients (aged 40-100 years) comparing them to younger healthy subjects. This was followe ...[more]

PMID: 31130473

Similar Datasets

Project description:The current study has investigated the hypothalamic gene expressions regulated by glucocorticoid (GC), key hormones in energy homeostasis. Using serial analysis of gene expression (SAGE) method, we have studied the effects of adrenalectomy (ADX) and GC on the transcriptomes of mouse hypothalamus. Approximately, 180 000 SAGE tags, which correspond to 50 000 tag species, were isolated from each group of intact or adrenalectomized mice, as well as 1, 3 and 24 hours after GC injection. ADX has upregulated diazepam binding inhibitor gene expression, while downregulating vomeronasal 1 receptor D4, genes involved in mitochondrial phosphorylation (cytochrome c oxidase 1 and NADH dehydrogenase 3), 3b-hydroxysteroid dehydrogenase-1, and prostaglandin D2 synthase. GC has increased the gene expression levels of dehydrogenase/reductase member 3, prostaglandin D2 synthase, solute carrier family 4 member 4, and five cytoskeletal proteins including myosin light chain phosphorylatable fast and troponin C2 fast. On the other hand, GC has reduced the mRNA levels of calmodilin 1 and expressed sequence tag similar to (EST) calmodilin 2, ATP synthase F0 subunit 6, and solute carrier family 4 member 3. Moreover, seven uncharacterized and 43 novel transcripts were modulated by ADX and GC. The current study has identified genes that may regulate hypothalamic systems governing energy balance in response to ADX and GC. Keywords: Hormone effect analysis Male C57BL6 mice were obtained from Charles River Laboratories (St. Constant, QC, Canada), at 12-14 weeks of age. Mice were housed in an air-conditioned room (19-25 degree) with controlled lighting from 07:15 to 19:15 h and were given free access to food (Lab Rodent Diet No. 5002) and water. One week prior to sampling of hypothalamus, adrenalectomy was performed in mice of all experimental groups (n = 12 per group). ADX mice received sodium chloride (0.9g/dl) in their drinking water after the surgery. GC (corticosterone, 0.1 mg per mouse) was subcutaneously injected to ADX mice and the hypothalamus was harvested at 1 hour (ADX + GC 1 h), 3 hours (ADX + GC 3 h) and 24 hours (ADX + GC 24 h) after the GC injection. ADX received an injection of vehicle solution (5% ethanol with 0.4% methocel A15LV premium) at 24 hours prior to sacrifice. All mice were killed between 08:30 and 12:30 by decapitation under isoflurane anesthesia. Brain was removed from the skull and the hypothalamus was immediately dissected, frozen in liquid nitrogen, pooled together for each group, and stored at -80 degree until RNA extraction.

Dataset Information

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

Background

Methods

Findings

Interpretation

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets