The Insulin-like Growth Factor 1 Receptor Induces Physiological Heart Growth via the Phosphoinositide 3-Kinase(p110α) Pathway

McMullen, Julie R.; Shioi, Tetsuo; Huang, Weei Yuarn; Zhang, Li; Tarnavski, Oleg; Bisping, Egbert; Schinke, Martina; Kong, Sek Won; Sherwood, Megan C.; Brown, Jeffrey L.; Riggi, Lauren; Kang, Peter M.; Izumo, Seigo

doi:10.1074/jbc.m310405200

Cited by 374 publications

(365 citation statements)

References 84 publications

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“…Interestingly, IGF1R RNA levels were elevated in KO-AL mice in comparison to N-AL and also in young, 3-month-old KO mice, while hGH transgenic mice had reduced level of IGF1R message. Because IGF1R can activate IRS1 and IRS2 just like IR, this can explain higher levels of these substrates in young KO mice in which IR RNA levels were not elevated (42). Study of IGF1R transgenic mice showed that over expressed IGF1R can cause enlargement of the heart (42).…”

Section: Insulin-like Growth Factor-1 and Insulin-like Growth Factor-mentioning

confidence: 99%

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Masternak¹,

Al-Regaiey²,

Lim³

et al. 2006

Experimental Gerontology

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Blockade of growth hormone (GH), decreased insulin-like growth factor-1 (IGF1) action and increased insulin sensitivity are associated with life extension and an apparent slowing of the aging process. We examined expression of genes involved in insulin action, IR, IRS1, IRS2, IGF1, IGF1R, GLUT4, PPARs and RXRs in the hearts of normal and GHR−/− (KO) mice fed ad libitum or subjected to 30% caloric restriction (CR). CR increased the cardiac expression of IR, IRS1, IGF1, IGF1R and GLUT4 in normal mice and IRS1, GLUT4, PPARα and PPARβ/δ in GHR-KO animals. Expression of IR, IRS1, IRS2, IGF1, GLUT4, PPARγ and PPARα did not differ between GHR-KO and normal mice. These unexpected results suggest that CR may lead to major modifications of insulin action in the heart, but high insulin sensitivity of GHR-KO mice is not associated with alterations in the levels of most of the examined molecules related to intracellular insulin signaling.

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Section: Insulin-like Growth Factor-1 and Insulin-like Growth Factor-mentioning

confidence: 99%

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Masternak¹,

Al-Regaiey²,

Lim³

et al. 2006

Experimental Gerontology

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“…The PI3K pathway was documented to regulate a number of physiological functions, including cell growth, survival and actin cytoskeleton rearrangement [57]. It was documented to be involved in a physiological hypertrophy of cardiomyocytes [58,59] as well as in the response of endothelial cells [60], keratinocytes and epithelial cells to stimulation with DC fields [61]. In activated platelets, PI3-kinase associates with cytoskeleton when significant actin polymerization occurs [62].…”

Section: Significance Of the Findingsmentioning

confidence: 99%

Interactive effects of surface topography and pulsatile electrical field stimulation on orientation and elongation of fibroblasts and cardiomyocytes

Au¹,

Cheng²,

Chowdhury³

et al. 2007

Biomaterials

177

166

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In contractile tissues such as myocardium, functional properties are directly related to the cellular orientation and elongation. Thus, tissue engineering of functional cardiac patches critically depends on our understanding of the interaction between multiple guidance cues such as topographical, adhesive or electrical. The main objective of this study was to determine the interactive effects of contact guidance and electrical field stimulation on elongation and orientation of fibroblasts and cardiomyocytes, major cell populations of the myocardium. Polyvinyl surfaces were abraded using lapping paper with grain size 1 to 80μm, resulting in V-shaped abrasions with the average abrasion peak-to-peak width in the range from 3 to 13μm, and the average depth in the range from 140nm to 700nm (AFM). The surfaces with abrasions 13μm wide and 700nm deep, exhibited the strongest effect on neonatal rat cardiomyocyte elongation and orientation as well as statistically significant effect on orientation of fibroblasts, thus they were utilized for electrical field stimulation. Electrical field stimulation was performed using a regime of relevance for heart tissue in vivo as well as for cardiac tissue engineering. Stimulation (square pulses, 1ms duration, 1Hz, 2.3V/cm or 4.6V/cm) was initiated 24hr after cell seeding and maintained for additional 72hr. The cover slips were positioned between the carbon rod electrodes so that the abrasions were either parallel or perpendicular to the field lines. Non-abraded surfaces were utilized as controls. Field stimulation did not affect cell viability (live/dead staining). The presence of a well developed contractile apparatus in neonatal rat cardiomyocytes (staining for cardiac Troponin I and actin filaments) was identified in the groups cultivated on abraded surfaces in the presence of field stimulation. Overall we observed that i) fibroblast and cardiomyocyte elongation on non-abraded surfaces was significantly enhanced by electrical field stimulation ii) electrical field stimulation promoted orientation of fibroblasts in the direction perpendicular to the field lines when the abrasions were also placed perpendicular to the field lines and iii) topographical cues were a significantly stronger determinant of cardiomyocyte orientation than the electrical field stimulation. The orientation and elongation response of cardiomyocytes was completely abolished by inhibition of actin polymerization (Cytochalasin D) and only partially by inhibition of phosphatidyl-inositol 3 kinase (PI3K) pathway (LY294002).

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“…In addition, IGF1R, an established factor in cardiac hypertrophy, is overexpressed in hypertrophic heart mediating the hypertrophic pathology process. In particular, it has been shown that the short-term activation of IGF signaling pathway promotes physiologic growth, whereas sustained hyperactivation leads to the development of pathologic hypertrophy and HF [36,37]. Interestingly, we observed that the expression of IGF-1R and myocardial hypertrophy in SD heart, are lower than those of HDF heart, suggesting that SD diet protects the heart from obesity dependent hypertrophy.…”

Section: Discussionmentioning

confidence: 56%

The innovative “Bio-Oil Spread” prevents metabolic disorders and mediates preconditioning-like cardioprotection in rats

Quintieri

Filice

Amelio

et al. 2016

Nutrition, Metabolism and Cardiovascular Diseases

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Background and aims: Obesity is often associated with an increased cardiovascular risk. The food industry and the associated research activities focus on formulating products that are a perfect mix between an adequate fat content and health. We evaluated whether a diet enriched with Bio-Oil Spread (SD), an olive oil-based innovative food, is cardioprotective in the presence of high-fat diet (HFD)-dependent obesity.Methods and Results: Rats were fed for 16 weeks with normolipidic diet (ND; fat: 6.2%), HFD (fat: 42%), and ND enriched with SD (6.2% of fat þ 35.8% of SD). Metabolic and anthropometric parameters were measured. Heart and liver structures were analyzed by histochemical examination. Ischemic susceptibility was evaluated on isolated and Langendorff-perfused cardiac preparations. Signaling was assessed by Western blotting. Compared to ND rats, HFD rats showed increased body weight and abdominal obesity, dyslipidemia, and impaired glucose tolerance. Morphological analyses showed that HFD is associated with heart and liver modifications (hypertrophy and steatosis, respectively), lesser evident in the SD group, together with metabolic and anthropometric alterations. In particular, IGF-1R immunodetection revealed a reduction of hypertrophy in SD heart sections. Notably, SD diet significantly reduced myocardial susceptibility against ischemia/reperfusion (I/R) with respect to HFD through the activation of survival signals (Akt, ERK1/2, and Bcl2). Systolic and diastolic performance was preserved in the SD group. Conclusions: We suggest that SD may contribute to the prevention of metabolic disorders and cardiovascular alterations typical of severe obesity induced by an HFD, including the increased ischemic susceptibility of the myocardium. Our results pave the way to evaluate the introduction of SD in human alimentary guidelines as a strategy to reduce saturated fat intake. IntroductionMen and women of all ages, races, and ethnic groups can be affected by obesity [1] and this is often accompanied by an increased morbidity and mortality due an increase of cardiovascular disease (CVD) risk factors [2,3]. Severe obesity causes permanent hemodynamic alterations that progressively impair cardiac structure and function. When comorbidities (i.e., systemic hypertension, sleep apnea, and hypoventilation) are present together with obesity, cardiac alterations progress to heart failure (HF) [4]. Metabolic syndrome (MetS) is a condition in which a high CVD risk is associated with obesity. It is characterized by disturbed glucose homeostasis, dyslipidemia, and hypertension [5] and is established in the presence of three of the following parameters: (i) waist circumference >40 (men) and >35 (women) inches; (ii) triglycerides >150 mg/dl; (iii) HDL (high-density lipoprotein) cholesterol <40 (men) and <50 (women) mg/dl; (iv) blood pressure >130/85 mm Hg; and (v) fasting glucose >100 mg/dl [6]. Currently, nutritional therapy is regarded as the best practice to prevent and/or reduce the cardiovascular damages associated ...

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The Insulin-like Growth Factor 1 Receptor Induces Physiological Heart Growth via the Phosphoinositide 3-Kinase(p110α) Pathway

Cited by 374 publications

References 84 publications

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Caloric restriction and growth hormone receptor knockout: Effects on expression of genes involved in insulin action in the heart

Interactive effects of surface topography and pulsatile electrical field stimulation on orientation and elongation of fibroblasts and cardiomyocytes

The innovative “Bio-Oil Spread” prevents metabolic disorders and mediates preconditioning-like cardioprotection in rats

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