Downregulation of miR-26b-5p, miR-204-5p, and miR-497-3p Expression Facilitates Exercise-Induced Physiological Cardiac Hypertrophy by Augmenting Autophagy in Rats

The insulin-like growth factor 1 receptor (IGF1R) and phosphoinositide 3-kinase p110a (PI3K) are critical regulators of exercise-induced physiological cardiac hypertrophy, and provide protection in experimental models of pathological remodeling and heart failure. Forkhead box class O1 (FoxO1) is a transcription factor which regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K activation in vitro, but its role in physiological hypertrophy in vivo was unknown. We generated cardiomyocyte-specific FoxO1 knockout (cKO) mice and assessed the phenotype under basal conditions and settings of physiological hypertrophy induced by 1) swim training, or 2) cardiac-specific transgenic expression of constitutively active PI3K (caPI3KTg+). Under basal conditions, male and female cKO mice displayed mild interstitial fibrosis compared with control (CON) littermates, but no other signs of cardiac pathology were present. In response to exercise training, female CON mice displayed an increase (~21%) in heart weight normalized to tibia length vs untrained mice. Exercise-induced hypertrophy was blunted in cKO mice. Exercise increased cardiac Akt phosphorylation and IGF1R expression, but was comparable between genotypes. However, differences in Foxo3a, Hsp70 and autophagy markers were identified in hearts of exercised cKO mice. Deletion of FoxO1 did not reduce cardiac hypertrophy in male or female caPI3KTg+ mice. Cardiac Akt and FoxO1 protein expression were significantly reduced in hearts of caPI3KTg+ mice, which may represent a negative feedback mechanism from chronic caPI3K, and negate any further effect of reducing FoxO1 in the cKO. In summary, FoxO1 contributes to exercise-induced hypertrophy. This has important implications when considering FoxO1 as a target for treating the diseased heart.

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Bioinformatics Analysis Reveals MicroRNAs Regulating Biological Pathways in Exercise-Induced Cardiac Physiological Hypertrophy

BioMed Research International ◽

10.1155/2017/2850659 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Jiahong Xu ◽

Yang Liu ◽

Yuan Xie ◽

Cuimei Zhao ◽

Hongbao Wang

Keyword(s):

Cardiac Hypertrophy ◽

Target Genes ◽

Arrhythmogenic Right Ventricular Cardiomyopathy ◽

Biological Pathways ◽

Receptor Interaction ◽

Ventricular Cardiomyopathy ◽

Functional Annotations ◽

Physiological Cardiac Hypertrophy ◽

Exercise Induced ◽

Physiological Hypertrophy

Exercise-induced physiological cardiac hypertrophy is generally considered to be a type of adaptive change after exercise training and is beneficial for cardiovascular diseases. This study aims at investigating exercise-regulated microRNAs (miRNAs) and their potential biological pathways. Here, we collected 23 miRNAs from 8 published studies. MirPath v.3 from the DIANA tools website was used to execute the analysis, and TargetScan was used to predict the target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to identify potential pathways and functional annotations associated with exercise-induced physiological cardiac hypertrophy. Various miRNA targets and molecular pathways, such as Fatty acid elongation, Arrhythmogenic right ventricular cardiomyopathy (ARVC), and ECM-receptor interaction, were identified. This study could prompt the understanding of the regulatory mechanisms underlying exercise-induced physiological cardiac hypertrophy.

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Forkhead box protein O1 (FoxO1) is required for exercise-induced, but not PI3K-induced, physiological cardiac hypertrophy

Journal of Molecular and Cellular Cardiology ◽

10.1016/j.yjmcc.2018.07.037 ◽

2018 ◽

Vol 124 ◽

pp. 93

Author(s):

Kate Weeks ◽

Helen Kiriazis ◽

Yow Keat Tham ◽

Bianca Bernardo ◽

Nelly Cemerlang ◽

...

Keyword(s):

Cardiac Hypertrophy ◽

Forkhead Box ◽

Physiological Cardiac Hypertrophy ◽

Exercise Induced

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Molecular Mechanisms of Nigella sativa- and Nigella sativa Exercise-Induced Cardiac Hypertrophy in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5553022 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Lubna Ibrahim Al Asoom

Keyword(s):

Exercise Training ◽

Cardiac Hypertrophy ◽

Molecular Mechanisms ◽

Nigella Sativa ◽

Male Rats ◽

Cell Diameter ◽

Vigorous Exercise ◽

Physiological Cardiac Hypertrophy ◽

Igf I ◽

Exercise Induced

Background. In our lab, we demonstrated cardiac hypertrophy induced by long-term administration of Nigella sativa (Ns) with enhanced function. Therefore, we aim to investigate the molecular mechanisms of Ns-induced cardiac hypertrophy, compare it with that induced by exercise training, and explore any possible synergistic effect of these two interventions. Method. Twenty adult Wistar male rats were divided into control (C), Ns-fed (N.s.), exercise-trained (Ex.), Ns-fed exercise-trained (N.s.Ex.) groups. 800 mg/kg of Ns was administered orally to N.s. rats. Ex. rats were trained on a treadmill with speed 18 m/min and grade 32° for two hours daily, and the N.s.Ex. group underwent both interventions. After 8 weeks, Immunohistochemical slides of the left ventricles were prepared using rat growth hormone (GH), insulin-like growth factor I (IGF-I), angiotensin-II receptors 1 (AT-I), endothelin-I (ET-1), Akt-1, and Erk-1. Cell diameter and number of nuclei were measured. Results. Cardiomyocyte diameter, number of nuclei, GH, and Akt were significantly higher in N.s, Ex., and N.s.Ex groups compared with the controls. IGF-I, AT-1, and ET-1 were significantly higher in Ex. rats only compared with the controls. Erk-1 was lower in N.s., Ex., and N.s.Ex. compared with the controls. Conclusion. We can conclude that Ns-induced cardiac hypertrophy is mediated by the GH-IGF I-PI3P-Akt pathway. Supplementation of Ns to exercise training protocol can block the upregulation of AT-I and ET-1. The combined N.s. exercise-induced cardiac hypertrophy might be a superior model of physiological cardiac hypertrophy and be used as a prophylactic therapy for athletes who are engaged in vigorous exercise activity.

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miR-199-sponge transgenic mice develop physiological cardiac hypertrophy

Cardiovascular Research ◽

10.1093/cvr/cvw052 ◽

2016 ◽

Vol 110 (2) ◽

pp. 258-267 ◽

Cited By ~ 24

Author(s):

Zhenhua Li ◽

Lantao Liu ◽

Ning Hou ◽

Yao Song ◽

Xiangbo An ◽

...

Keyword(s):

Transgenic Mice ◽

Cardiac Hypertrophy ◽

Physiological Cardiac Hypertrophy

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Insulin-Like Growth Factor I Receptor Signaling Is Required for Exercise-Induced Cardiac Hypertrophy

Molecular Endocrinology ◽

10.1210/me.2008-0265 ◽

2008 ◽

Vol 22 (11) ◽

pp. 2531-2543 ◽

Cited By ~ 119

Author(s):

Jaetaek Kim ◽

Adam R. Wende ◽

Sandra Sena ◽

Heather A. Theobald ◽

Jamie Soto ◽

...

Keyword(s):

Growth Factor ◽

Cardiac Hypertrophy ◽

Insulin Like Growth Factor ◽

Receptor Signaling ◽

Factor I ◽

Growth Factor I ◽

Exercise Induced

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Effects of Hypertension and Exercise on Cardiac Proteome Remodelling

BioMed Research International ◽

10.1155/2014/634132 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 12

Author(s):

Bernardo A. Petriz ◽

Octavio L. Franco

Keyword(s):

Cardiac Hypertrophy ◽

Pressure Overload ◽

Molecular Characteristics ◽

Hypertension Treatment ◽

Ischemic Insult ◽

Left Ventricle Hypertrophy ◽

Exercise Induced ◽

Ventricle Hypertrophy ◽

Related Proteins ◽

Proteomic Research

Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression, and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and isoproterenol. Several metabolic, contractile, and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a nonpharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive-induced and exercise-induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined.

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