Abstract

BackgroundChronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Inhibition of autophagic capacity with ageing was postulated to generate a pro-inflammatory condition via activation of inflammasomes, a group of Interleukin-1 activating intracellular multi-protein complexes. We thus investigated gene expression of inflammasome components in PBMC of 77 vascular patients (age 22–82) in association with age.FindingsLinear regression of real-time qRT-PCR data revealed a significant positive association of gene expression of each of the inflammasome components with age (Pearson correlation coefficients: AIM2: r = 0.245; P = 0.032; NLRP3: r = 0.367; P = 0.001; ASC (PYCARD): r = 0.252; P = 0.027; CASP1: r = 0.296; P = 0.009; CASP5: r = 0.453; P = 0.00003; IL1B: r = 0.247; P = 0.030). No difference in gene expression of AIM2, NLRP3, ASC CASP1, and CASP5 was detected between PBMC of patients with advanced atherosclerosis and other vascular patients, whereas IL1B expression was increased in PBMC of the latter group (P = 0.0005).ConclusionThe findings reinforce the systemic pro-inflammatory phenotype reported in elderly by demonstrating an increased phase-1 activation of inflammasomes in PBMC of vascular patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12979-015-0043-y) contains supplementary material, which is available to authorized users.

Highlights

  • Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases

  • Materials and methods Venous blood was taken from 77 vascular patients on the day of their hospitalization according to the standard operating procedures of the Vascular Biobank Heidelberg (VBBH)

  • The strongest correlation was found for CASP5 with a correlation coefficient of 0.468 (P = 0.00003)

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Summary

Introduction

Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Conclusion: The findings reinforce the systemic pro-inflammatory phenotype reported in elderly by demonstrating an increased phase-1 activation of inflammasomes in PBMC of vascular patients. Expression levels of the inflammasome components are generally low and require a two phase induction: A priming phase stimulates gene expression of inactive precursors before a second signal can stimulate assembly of the multiprotein complex consisting of sensor proteins, the adaptor protein apoptosis-associated specklike protein with a caspase activation and recruitment domain (ASC) and inflammatory caspases (Caspase-1 or Caspase-5).

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