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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 is associated with mild weight loss and reduces infarct size following permanent LAD ligation.(A) Schematic of the protocol adopted for short-term caloric restriction (CR) with control groups AL (ad libitum) and sAL (stressed ad libitum), (B) Percent weight change over 7d shows an 8.5% weight loss in CR, with 8.6% and 6.7% weight gain in AL and sAL, respectively. (C) Representative TTC stained cardiac slices and (D) quantitative analysis of infarct size at 2 d post LAD ligation showing reduced infarct size in the CR group compared to AL and sAL controls (18.45±2.41 vs. 26.55±1.69 and 28.7±3.6; respectively, N = 15/group, 1-way ANOVA and Tukey post hoc test, P = 0.01). (E) Representative Western blots for cleaved caspase-3 performed on total lysates from hearts obtained d2 post-MI reveal reduced induction of this apoptosis marker in CR-treated animals.
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pone.0130658.g001: Short-term CR is associated with mild weight loss and reduces infarct size following permanent LAD ligation.(A) Schematic of the protocol adopted for short-term caloric restriction (CR) with control groups AL (ad libitum) and sAL (stressed ad libitum), (B) Percent weight change over 7d shows an 8.5% weight loss in CR, with 8.6% and 6.7% weight gain in AL and sAL, respectively. (C) Representative TTC stained cardiac slices and (D) quantitative analysis of infarct size at 2 d post LAD ligation showing reduced infarct size in the CR group compared to AL and sAL controls (18.45±2.41 vs. 26.55±1.69 and 28.7±3.6; respectively, N = 15/group, 1-way ANOVA and Tukey post hoc test, P = 0.01). (E) Representative Western blots for cleaved caspase-3 performed on total lysates from hearts obtained d2 post-MI reveal reduced induction of this apoptosis marker in CR-treated animals.

Mentions: All data are expressed as mean ± SE. Un-paired Student’s t test was used to compare data shown in Fig 1. Statistical analysis and visualization of microarray data was performed using Partek version 6.3 [Partek Inc] and GX11 [Agilent] software. qPCR data shown are mean ± SEM. Statistical analyses of qPCR data were performed by Student's unpaired t-test or One-way ANOVA followed by Tukey's for multiple comparisons. Analyses were performed on Graphpad Prism v5.0 (GraphPad Software, Inc., La Jolla, CA, USA).


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 is associated with mild weight loss and reduces infarct size following permanent LAD ligation.(A) Schematic of the protocol adopted for short-term caloric restriction (CR) with control groups AL (ad libitum) and sAL (stressed ad libitum), (B) Percent weight change over 7d shows an 8.5% weight loss in CR, with 8.6% and 6.7% weight gain in AL and sAL, respectively. (C) Representative TTC stained cardiac slices and (D) quantitative analysis of infarct size at 2 d post LAD ligation showing reduced infarct size in the CR group compared to AL and sAL controls (18.45±2.41 vs. 26.55±1.69 and 28.7±3.6; respectively, N = 15/group, 1-way ANOVA and Tukey post hoc test, P = 0.01). (E) Representative Western blots for cleaved caspase-3 performed on total lysates from hearts obtained d2 post-MI reveal reduced induction of this apoptosis marker in CR-treated animals.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130658.g001: Short-term CR is associated with mild weight loss and reduces infarct size following permanent LAD ligation.(A) Schematic of the protocol adopted for short-term caloric restriction (CR) with control groups AL (ad libitum) and sAL (stressed ad libitum), (B) Percent weight change over 7d shows an 8.5% weight loss in CR, with 8.6% and 6.7% weight gain in AL and sAL, respectively. (C) Representative TTC stained cardiac slices and (D) quantitative analysis of infarct size at 2 d post LAD ligation showing reduced infarct size in the CR group compared to AL and sAL controls (18.45±2.41 vs. 26.55±1.69 and 28.7±3.6; respectively, N = 15/group, 1-way ANOVA and Tukey post hoc test, P = 0.01). (E) Representative Western blots for cleaved caspase-3 performed on total lysates from hearts obtained d2 post-MI reveal reduced induction of this apoptosis marker in CR-treated animals.
Mentions: All data are expressed as mean ± SE. Un-paired Student’s t test was used to compare data shown in Fig 1. Statistical analysis and visualization of microarray data was performed using Partek version 6.3 [Partek Inc] and GX11 [Agilent] software. qPCR data shown are mean ± SEM. Statistical analyses of qPCR data were performed by Student's unpaired t-test or One-way ANOVA followed by Tukey's for multiple comparisons. Analyses were performed on Graphpad Prism v5.0 (GraphPad Software, Inc., La Jolla, CA, USA).

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