The IGF1-PI3K-Akt Signaling Pathway in Mediating Exercise-Induced Cardiac Hypertrophy and Protection
Regular physical activity or exercise training can lead to heart enlargement known as cardiac hypertrophy. Cardiac hypertrophy is broadly defined as an increase in heart mass. In adults, cardiac hypertrophy is often considered a poor prognostic sign becau
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The IGF1-PI3K-Akt Signaling Pathway in Mediating Exercise-Induced Cardiac Hypertrophy and Protection Kate L. Weeks, Bianca C. Bernardo, Jenny Y.Y. Ooi, Natalie L. Patterson, and Julie R. McMullen Abstract Regular physical activity or exercise training can lead to heart enlargement known as cardiac hypertrophy. Cardiac hypertrophy is broadly defined as an increase in heart mass. In adults, cardiac hypertrophy is often considered a poor prognostic sign because it often progresses to heart failure. Heart enlargement in a setting of cardiac disease is referred to as pathological cardiac hypertrophy and is typically characterized by cell death and depressed cardiac function. By contrast, physiological cardiac hypertrophy, as occurs in response to chronic exercise training (i.e. the ‘athlete’s heart’), is associated with normal or enhanced cardiac function. The following chapter describes the morphologically distinct types of heart growth, and the key role of the insulin-like growth factor 1 (IGF1) – phosphoinositide 3-kinase (PI3K)-Akt signaling pathway in regulating exercise-induced physiological cardiac hypertrophy and cardiac protection. Finally we summarize therapeutic approaches that target the IGF1-PI3K-Akt signaling pathway which are showing promise in preclinical models of heart disease. Keywords IGF1-PI3K-Akt signaling • Exercise • Heart
1 Introduction In adults, heart enlargement, also known as cardiac hypertrophy, is usually considered a poor prognostic sign because it often progresses to heart failure. Consequently, there has been great interest in examining the molecular mechanisms responsible for the induction of cardiac hypertrophy and transition to heart failure. It is also recognized that not all forms of cardiac hypertrophy progress to failure. In response to regular exercise training, the heart enlarges, but this can protect the heart against K.L. Weeks (*) • B.C. Bernardo • J.Y.Y. Ooi • N.L. Patterson • J.R. McMullen (*) Baker Heart & Diabetes Institute, P.O. Box 6492, Melbourne, VIC 3004, Australia e-mail: [email protected]; [email protected] © Springer Nature Singapore Pte Ltd. 2017 J. Xiao (ed.), Exercise for Cardiovascular Disease Prevention and Treatment, Advances in Experimental Medicine and Biology 1000, DOI 10.1007/978-981-10-4304-8_12
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cardiac disease and heart failure. This type of heart enlargement is typically referred to as physiological cardiac hypertrophy or the “athlete’s heart”. The following chapter describes the morphologically distinct types of heart growth, and the key role of the insulin-like growth factor 1 (IGF1)-phosphoinositide 3-kinase (PI3K)-Akt signaling pathway in regulating exercise-induced physiological cardiac hypertrophy and cardiac protection. Finally, we summarize therapeutic approaches that target the IGF1-PI3K-Akt signaling pathway which are showing promise in preclinical models of heart disease.
2 C ardiac Hypertrophy and the Association with Heart Failure Versus Cardiac Protection Cardiac hypertrophy refers
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