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Cardioprotective Signature of Short-Term Caloric Restriction.

Noyan H, El-Mounayri O, Isserlin R, Arab S, Momen A, Cheng HS, Wu J, Afroze T, Li RK, Fish JE, Bader GD, Husain M - PLoS ONE (2015)

Bottom Line: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). mRNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM).Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38).CR regimen was also associated with reduced protein abundance of cleaved caspase 3 in the infarcted heart and improved cardiac function.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Therapeutics, Toronto General Research Institute, Toronto, Ontario, Canada.

ABSTRACT

Objective: To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR).

Background: Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we reveal the pathways that are modulated by short-term CR, which are associated with protection of the mouse heart from ischemia.

Methods: Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food for 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. At d8, the left ventricles (LV) of AL and CR mice were collected for Western blot, mRNA and microRNA (miR) analyses to identify cardioprotective gene expression signatures. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI.

Results: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). mRNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CR regimen was also associated with reduced protein abundance of cleaved caspase 3 in the infarcted heart and improved cardiac function.

No MeSH data available.


Related in: MedlinePlus

Short-term CR improved cardiac function post-MI.(A) Representative steady state pressure-volume (PV) loop recordings in the two treatment groups pre- (D8 of diet = D0-MI) and 2 days post-MI (D2-MI). (B–F) Grouped results of PV analyses reveal differences in systolic (ejection fraction, dP/dt-max and end-systolic volume) and diastolic function (dP/dtmin and Tau) in favor of CR- vs. sAL-treated mice (*P<0.05 and **P<0.01 respectively).
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pone.0130658.g002: Short-term CR improved cardiac function post-MI.(A) Representative steady state pressure-volume (PV) loop recordings in the two treatment groups pre- (D8 of diet = D0-MI) and 2 days post-MI (D2-MI). (B–F) Grouped results of PV analyses reveal differences in systolic (ejection fraction, dP/dt-max and end-systolic volume) and diastolic function (dP/dtmin and Tau) in favor of CR- vs. sAL-treated mice (*P<0.05 and **P<0.01 respectively).

Mentions: Invasive pressure-volume measurements (Fig 2) showed reduced systolic function with lower dP/dt max (first derivative of pressure during isovolumic contraction) and ejection fraction as well as larger end-systolic volume in AL vs. CR mice at 2d post-MI. Reduced first derivative of pressure during isovolumic relaxation (dP/dt min) coupled with prolonged time constant of isovolumic relaxation (tau) suggested abnormalities in myocardial energetics and stiffness in AL vs CR mice after severe ischemic insult. Importantly, there were no differences between the sAL and CR groups in any of the hemodynamic parameters prior to MI (0d).


Cardioprotective Signature of Short-Term Caloric Restriction.

Noyan H, El-Mounayri O, Isserlin R, Arab S, Momen A, Cheng HS, Wu J, Afroze T, Li RK, Fish JE, Bader GD, Husain M - PLoS ONE (2015)

Short-term CR improved cardiac function post-MI.(A) Representative steady state pressure-volume (PV) loop recordings in the two treatment groups pre- (D8 of diet = D0-MI) and 2 days post-MI (D2-MI). (B–F) Grouped results of PV analyses reveal differences in systolic (ejection fraction, dP/dt-max and end-systolic volume) and diastolic function (dP/dtmin and Tau) in favor of CR- vs. sAL-treated mice (*P<0.05 and **P<0.01 respectively).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476723&req=5

pone.0130658.g002: Short-term CR improved cardiac function post-MI.(A) Representative steady state pressure-volume (PV) loop recordings in the two treatment groups pre- (D8 of diet = D0-MI) and 2 days post-MI (D2-MI). (B–F) Grouped results of PV analyses reveal differences in systolic (ejection fraction, dP/dt-max and end-systolic volume) and diastolic function (dP/dtmin and Tau) in favor of CR- vs. sAL-treated mice (*P<0.05 and **P<0.01 respectively).
Mentions: Invasive pressure-volume measurements (Fig 2) showed reduced systolic function with lower dP/dt max (first derivative of pressure during isovolumic contraction) and ejection fraction as well as larger end-systolic volume in AL vs. CR mice at 2d post-MI. Reduced first derivative of pressure during isovolumic relaxation (dP/dt min) coupled with prolonged time constant of isovolumic relaxation (tau) suggested abnormalities in myocardial energetics and stiffness in AL vs CR mice after severe ischemic insult. Importantly, there were no differences between the sAL and CR groups in any of the hemodynamic parameters prior to MI (0d).

Bottom Line: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). mRNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM).Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38).CR regimen was also associated with reduced protein abundance of cleaved caspase 3 in the infarcted heart and improved cardiac function.

View Article: PubMed Central - PubMed

Affiliation: Division of Experimental Therapeutics, Toronto General Research Institute, Toronto, Ontario, Canada.

ABSTRACT

Objective: To understand the molecular pathways underlying the cardiac preconditioning effect of short-term caloric restriction (CR).

Background: Lifelong CR has been suggested to reduce the incidence of cardiovascular disease through a variety of mechanisms. However, prolonged adherence to a CR life-style is difficult. Here we reveal the pathways that are modulated by short-term CR, which are associated with protection of the mouse heart from ischemia.

Methods: Male 10-12 wk old C57bl/6 mice were randomly assigned to an ad libitum (AL) diet with free access to regular chow, or CR, receiving 30% less food for 7 days (d), prior to myocardial infarction (MI) via permanent coronary ligation. At d8, the left ventricles (LV) of AL and CR mice were collected for Western blot, mRNA and microRNA (miR) analyses to identify cardioprotective gene expression signatures. In separate groups, infarct size, cardiac hemodynamics and protein abundance of caspase 3 was measured at d2 post-MI.

Results: This short-term model of CR was associated with cardio-protection, as evidenced by decreased infarct size (18.5±2.4% vs. 26.6±1.7%, N=10/group; P=0.01). mRNA and miR profiles pre-MI (N=5/group) identified genes modulated by short-term CR to be associated with circadian clock, oxidative stress, immune function, apoptosis, metabolism, angiogenesis, cytoskeleton and extracellular matrix (ECM). Western blots pre-MI revealed CR-associated increases in phosphorylated Akt and GSK3ß, reduced levels of phosphorylated AMPK and mitochondrial related proteins PGC-1α, cytochrome C and cyclooxygenase (COX) IV, with no differences in the levels of phosphorylated eNOS or MAPK (ERK1/2; p38). CR regimen was also associated with reduced protein abundance of cleaved caspase 3 in the infarcted heart and improved cardiac function.

No MeSH data available.


Related in: MedlinePlus