Compromised cardiovascular function in aged rats corresponds with increased expression and activity of calcium/calmodulin dependent protein kinase IIδ in aortic endothelium

Claire McCluskey, Laura Mooney, Andrew Paul, Susan Currie

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Abstract

Ageing is the greatest risk factor for cardiovascular disease. Calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) plays a fundamental role in the pathology of heart disease yet a potential role for CaMKIIδ in cardiovascular pathology associated with ageing remains unclear. Taking a combined in vivo and in vitro approach, we have for the first time investigated whether CaMKIIδ expression and CaMKII activity may be altered following age-related cardiovascular deterioration. Both cardiac contractility and aortic blood flow are compromised in aged rats and we have shown that this occurs in parallel with increased inflammation and crucially, autonomous activation of CaMKII. Endothelial cells isolated from young and aged aortae exhibit differences in cell phenotype and physiology. In line with observations in aortic tissue, aged aortic endothelial cells also show increased basal levels of pro-inflammatory markers and oxidative stress with concurrent increased basal activation of CaMKII. These results are the first to demonstrate that elevated CaMKIIδ expression and CaMKII activation occur in parallel with the pathological progression associated with ageing of the heart and vasculature. Specifically, CaMKIIδ expression is significantly increased and activated in the endothelium of aged aorta. As such, CaMKIIδ could serve as an important marker of endothelial dysfunction that accompanies the ageing process and may be an appropriate candidate for investigating targeted therapeutic intervention.
Original languageEnglish
Article number106560
Number of pages11
JournalVascular pharmacology
Volume118-119
Early online date30 Apr 2019
DOIs
Publication statusPublished - 31 Jul 2019

Keywords

  • ageing
  • cardiovascular
  • endothelium
  • calcium/calmodulin protein kinase II
  • inflammation
  • oxidative stress

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  • Projects

    BBSRC Doctoral Training Grant (DTG) | MacAskill, Mark

    Coats, P., Currie, S. & MacAskill, M.

    BBSRC (Biotech & Biological Sciences Research Council)

    1/10/108/04/14

    Project: Research Studentship - Internally Allocated

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