Cardioprotective Signature of Short-Term Caloric Restriction

• Published in: PloS one 2015-06, Vol.10 (6), p.e0130658-e0130658
• Main Authors: Noyan, Hossein, El-Mounayri, Omar, Isserlin, Ruth, Arab, Sara, Momen, Abdul, Cheng, Henry S, Wu, Jun, Afroze, Talat, Li, Ren-Ke, Fish, Jason E, Bader, Gary D, Husain, Mansoor
• Format: Article
• Language: English
• Subjects: Abundance; Aging; AKT protein; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Analysis; Angiogenesis; Animals; Apoptosis; Caloric Restriction; Cardiomyocytes; Cardiovascular disease; Cardiovascular diseases; Caspase; Caspase-3; Circadian rhythm; Circadian rhythms; Cytochrome; Cytochrome c; Cytochromes c - genetics; Cytochromes c - metabolism; Cytoskeleton; Diet; Dietary restrictions; Extracellular matrix; Extracellular signal-regulated kinase; Gene expression; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Health care networks; Heart; Heart attack; Heart diseases; Hemodynamics; Immune response; Infarction; Ischemia; Laboratories; Male; MAP kinase; Metabolism; Mice; Mice, Inbred C57BL; MicroRNAs; miRNA; Mitochondria; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Molecular chains; Munk, Peter; Myocardial infarction; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - prevention & control; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Oxidative stress; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Pathways; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Physiology; Preconditioning; Prostaglandin endoperoxide synthase; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Ribonucleic acid; RNA; Short term; Stroke; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptome; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130658

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