Calcium/calmodulin-dependent protein kinase II - does ageing mirror disease?

Claire McCluskey, Hanif Salleh, Susan Currie

Research output: Contribution to journalMeeting abstract

Abstract

Calcium/calmodulin–dependent protein kinase II delta (CaMKIId) plays a fundamental role in cardiac dysfunction and is known to be overexpressed and hyper-activated in the diseased heart. A role for CaMKIId in compromised cardiovascular function associated with ageing has yet to be established. Here we compare CaMKIId expression and oxidation (a novel route of enzyme activation) in the diseased and in the aged heart and vasculature. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy as our disease model, we investigated whether alterations in CaMKIId and oxidised CaMKII (ox-CaMKII) observed during cardiac disease are also a key feature of ageing, where oxidative stress is apparent. Myocardial function was assessed in vivo by echocardiography and compared with that of sham-operated animals. A significant increase in systolic blood pressure (110±6.3 vs 78±2.6, MTAB vs sham, n=4), mean arterial pressure (75±3.3 vs 60±2.6 (mmHg), MTAB vs sham) and reduction in fractional shortening (39.4±4.4 vs 53.6±3.8 (%FS) MTAB vs sham, n=7, p<0.05) was observed in the hearts from hypertrophied animals demonstrating successful surgical intervention. Post-mortem analysis revealed increased heart weight:body weight in MTAB animals (5.48±0.17 vs 4.32±0.01, MTAB vs sham, n=6, p<0.05). Quantitative immunoblotting of CaMKIId and ox-CaMKII expression in whole heart homogenates from MTAB animals showed significant up-regulation of both when compared to sham controls (0.68±0.02 vs 0.47±0.01 MTAB v’s sham, n=7, p<0.01). Interestingly, similar results were obtained in hearts from aged animals. A significant increase in CaMKIId expression was evident in aged hearts (0.81±0.08 vs. 0.46±0.08 aged vs young, p=0.04, n=3) and preliminary data suggests ox-CaMKII levels also show an increase in comparison to young (1.5-fold increase, n=1). Similar experiments were also conducted in young and aged rat aortae to assess CaMKIId involvement in vascular function. Vessels from aged subjects showed a significant increase in wall thickness (16.4±0.9 vs. 28±1.5 (um), young vs. aged, p=0.002, n=3) which may suggest an altered phenotype comparable to that observed during disease. Further quantitative immunoblotting indicated that CaMKIId is highly expressed in the vasculature and initial results suggest some alterations in ox-CaMKII protein levels with ageing, parallel to that observed in the heart. Overall, this work highlights for the first time that ageing alone, produces similar physiological and biochemical alterations in the heart as observed during cardiac disease. In addition to this, preliminary data from the vasculature has revealed a similar trend, suggesting CaMKIId may play an important role in overall deterioration of cardiovascular function with progressive ageing.
LanguageEnglish
Article number767.3
JournalFASEB Journal
Volume30
Issue number1 supplement
Publication statusPublished - 30 Apr 2016
EventExperimental Biology Meeting 2016 - San Diego, United States
Duration: 2 Apr 20166 Apr 2016
http://experimentalbiology.org/2016/Home.aspx

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Mirrors
Aging of materials
Animals
Heart Diseases
Immunoblotting
Blood Pressure
Echocardiography
Enzyme Activation
Oxidative stress
Blood pressure
Cardiomegaly
Blood Vessels
Deterioration
Aorta
Rats

Keywords

  • Calcium/calmodulin–dependent protein kinase II delta
  • CaMKIId
  • cardiac dysfunction
  • transverse aortic banding
  • myocardial function
  • echocardiography
  • progressive ageing

Cite this

McCluskey, Claire ; Salleh, Hanif ; Currie, Susan. / Calcium/calmodulin-dependent protein kinase II - does ageing mirror disease?. In: FASEB Journal. 2016 ; Vol. 30, No. 1 supplement.
@article{e1463eef8d0d416cb05ae1562d00e14d,
title = "Calcium/calmodulin-dependent protein kinase II - does ageing mirror disease?",
abstract = "Calcium/calmodulin–dependent protein kinase II delta (CaMKIId) plays a fundamental role in cardiac dysfunction and is known to be overexpressed and hyper-activated in the diseased heart. A role for CaMKIId in compromised cardiovascular function associated with ageing has yet to be established. Here we compare CaMKIId expression and oxidation (a novel route of enzyme activation) in the diseased and in the aged heart and vasculature. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy as our disease model, we investigated whether alterations in CaMKIId and oxidised CaMKII (ox-CaMKII) observed during cardiac disease are also a key feature of ageing, where oxidative stress is apparent. Myocardial function was assessed in vivo by echocardiography and compared with that of sham-operated animals. A significant increase in systolic blood pressure (110±6.3 vs 78±2.6, MTAB vs sham, n=4), mean arterial pressure (75±3.3 vs 60±2.6 (mmHg), MTAB vs sham) and reduction in fractional shortening (39.4±4.4 vs 53.6±3.8 ({\%}FS) MTAB vs sham, n=7, p<0.05) was observed in the hearts from hypertrophied animals demonstrating successful surgical intervention. Post-mortem analysis revealed increased heart weight:body weight in MTAB animals (5.48±0.17 vs 4.32±0.01, MTAB vs sham, n=6, p<0.05). Quantitative immunoblotting of CaMKIId and ox-CaMKII expression in whole heart homogenates from MTAB animals showed significant up-regulation of both when compared to sham controls (0.68±0.02 vs 0.47±0.01 MTAB v’s sham, n=7, p<0.01). Interestingly, similar results were obtained in hearts from aged animals. A significant increase in CaMKIId expression was evident in aged hearts (0.81±0.08 vs. 0.46±0.08 aged vs young, p=0.04, n=3) and preliminary data suggests ox-CaMKII levels also show an increase in comparison to young (1.5-fold increase, n=1). Similar experiments were also conducted in young and aged rat aortae to assess CaMKIId involvement in vascular function. Vessels from aged subjects showed a significant increase in wall thickness (16.4±0.9 vs. 28±1.5 (um), young vs. aged, p=0.002, n=3) which may suggest an altered phenotype comparable to that observed during disease. Further quantitative immunoblotting indicated that CaMKIId is highly expressed in the vasculature and initial results suggest some alterations in ox-CaMKII protein levels with ageing, parallel to that observed in the heart. Overall, this work highlights for the first time that ageing alone, produces similar physiological and biochemical alterations in the heart as observed during cardiac disease. In addition to this, preliminary data from the vasculature has revealed a similar trend, suggesting CaMKIId may play an important role in overall deterioration of cardiovascular function with progressive ageing.",
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McCluskey, C, Salleh, H & Currie, S 2016, 'Calcium/calmodulin-dependent protein kinase II - does ageing mirror disease?' FASEB Journal, vol. 30, no. 1 supplement, 767.3.

Calcium/calmodulin-dependent protein kinase II - does ageing mirror disease? / McCluskey, Claire; Salleh, Hanif; Currie, Susan.

In: FASEB Journal, Vol. 30, No. 1 supplement, 767.3, 30.04.2016.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Calcium/calmodulin-dependent protein kinase II - does ageing mirror disease?

AU - McCluskey, Claire

AU - Salleh, Hanif

AU - Currie, Susan

PY - 2016/4/30

Y1 - 2016/4/30

N2 - Calcium/calmodulin–dependent protein kinase II delta (CaMKIId) plays a fundamental role in cardiac dysfunction and is known to be overexpressed and hyper-activated in the diseased heart. A role for CaMKIId in compromised cardiovascular function associated with ageing has yet to be established. Here we compare CaMKIId expression and oxidation (a novel route of enzyme activation) in the diseased and in the aged heart and vasculature. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy as our disease model, we investigated whether alterations in CaMKIId and oxidised CaMKII (ox-CaMKII) observed during cardiac disease are also a key feature of ageing, where oxidative stress is apparent. Myocardial function was assessed in vivo by echocardiography and compared with that of sham-operated animals. A significant increase in systolic blood pressure (110±6.3 vs 78±2.6, MTAB vs sham, n=4), mean arterial pressure (75±3.3 vs 60±2.6 (mmHg), MTAB vs sham) and reduction in fractional shortening (39.4±4.4 vs 53.6±3.8 (%FS) MTAB vs sham, n=7, p<0.05) was observed in the hearts from hypertrophied animals demonstrating successful surgical intervention. Post-mortem analysis revealed increased heart weight:body weight in MTAB animals (5.48±0.17 vs 4.32±0.01, MTAB vs sham, n=6, p<0.05). Quantitative immunoblotting of CaMKIId and ox-CaMKII expression in whole heart homogenates from MTAB animals showed significant up-regulation of both when compared to sham controls (0.68±0.02 vs 0.47±0.01 MTAB v’s sham, n=7, p<0.01). Interestingly, similar results were obtained in hearts from aged animals. A significant increase in CaMKIId expression was evident in aged hearts (0.81±0.08 vs. 0.46±0.08 aged vs young, p=0.04, n=3) and preliminary data suggests ox-CaMKII levels also show an increase in comparison to young (1.5-fold increase, n=1). Similar experiments were also conducted in young and aged rat aortae to assess CaMKIId involvement in vascular function. Vessels from aged subjects showed a significant increase in wall thickness (16.4±0.9 vs. 28±1.5 (um), young vs. aged, p=0.002, n=3) which may suggest an altered phenotype comparable to that observed during disease. Further quantitative immunoblotting indicated that CaMKIId is highly expressed in the vasculature and initial results suggest some alterations in ox-CaMKII protein levels with ageing, parallel to that observed in the heart. Overall, this work highlights for the first time that ageing alone, produces similar physiological and biochemical alterations in the heart as observed during cardiac disease. In addition to this, preliminary data from the vasculature has revealed a similar trend, suggesting CaMKIId may play an important role in overall deterioration of cardiovascular function with progressive ageing.

AB - Calcium/calmodulin–dependent protein kinase II delta (CaMKIId) plays a fundamental role in cardiac dysfunction and is known to be overexpressed and hyper-activated in the diseased heart. A role for CaMKIId in compromised cardiovascular function associated with ageing has yet to be established. Here we compare CaMKIId expression and oxidation (a novel route of enzyme activation) in the diseased and in the aged heart and vasculature. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy as our disease model, we investigated whether alterations in CaMKIId and oxidised CaMKII (ox-CaMKII) observed during cardiac disease are also a key feature of ageing, where oxidative stress is apparent. Myocardial function was assessed in vivo by echocardiography and compared with that of sham-operated animals. A significant increase in systolic blood pressure (110±6.3 vs 78±2.6, MTAB vs sham, n=4), mean arterial pressure (75±3.3 vs 60±2.6 (mmHg), MTAB vs sham) and reduction in fractional shortening (39.4±4.4 vs 53.6±3.8 (%FS) MTAB vs sham, n=7, p<0.05) was observed in the hearts from hypertrophied animals demonstrating successful surgical intervention. Post-mortem analysis revealed increased heart weight:body weight in MTAB animals (5.48±0.17 vs 4.32±0.01, MTAB vs sham, n=6, p<0.05). Quantitative immunoblotting of CaMKIId and ox-CaMKII expression in whole heart homogenates from MTAB animals showed significant up-regulation of both when compared to sham controls (0.68±0.02 vs 0.47±0.01 MTAB v’s sham, n=7, p<0.01). Interestingly, similar results were obtained in hearts from aged animals. A significant increase in CaMKIId expression was evident in aged hearts (0.81±0.08 vs. 0.46±0.08 aged vs young, p=0.04, n=3) and preliminary data suggests ox-CaMKII levels also show an increase in comparison to young (1.5-fold increase, n=1). Similar experiments were also conducted in young and aged rat aortae to assess CaMKIId involvement in vascular function. Vessels from aged subjects showed a significant increase in wall thickness (16.4±0.9 vs. 28±1.5 (um), young vs. aged, p=0.002, n=3) which may suggest an altered phenotype comparable to that observed during disease. Further quantitative immunoblotting indicated that CaMKIId is highly expressed in the vasculature and initial results suggest some alterations in ox-CaMKII protein levels with ageing, parallel to that observed in the heart. Overall, this work highlights for the first time that ageing alone, produces similar physiological and biochemical alterations in the heart as observed during cardiac disease. In addition to this, preliminary data from the vasculature has revealed a similar trend, suggesting CaMKIId may play an important role in overall deterioration of cardiovascular function with progressive ageing.

KW - Calcium/calmodulin–dependent protein kinase II delta

KW - CaMKIId

KW - cardiac dysfunction

KW - transverse aortic banding

KW - myocardial function

KW - echocardiography

KW - progressive ageing

UR - http://www.fasebj.org/content/30/1_Supplement/767.3.abstract

M3 - Meeting abstract

VL - 30

JO - FASEB Journal

T2 - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

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