Insulin-like Growth Factor I as aÈCardiac Hormone: Physiological and Pathophysiological Implications in Heart Disease

Ren, Jun; Samson, Willis K.; Sowers, James R.

doi:10.1006/jmcc.1999.1036

Cited by 276 publications

(276 citation statements)

References 81 publications

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“…In the case of proliferation however, the effect of IGF1 was more pronounced in early passage of cells compared to the late passage. Decline of growth factors such like IGF-1 has been demonstrated with increased life cycle [41], which makes supplementation of growth factors including IGF-1, a reasonable strategy to maintain or regain lost physiological effects of these growth factors [25,42,43]. Interestingly, evidence has indicated that suppression of these growth factors or their receptors prolongs lifespan and delays in age-associated functional decline.…”

Section: Discussionmentioning

confidence: 99%

“…IGF-1 has a wide spectrum of physiological effects including regulation of cardiac contractility, tissue remodeling, glucose metabolism, insulin-sensitivity, and lipid profile, as well as vasomotor activity [25]. IGF-1 is thought to mediate these functions either via its antiapoptotic effect and/or its stimulatory effects on migration and proliferation, depending on the cell phenotype [8].…”

Section: Introductionmentioning

confidence: 99%

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Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

et al. 2007

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Migration and proliferation of vascular smooth muscle cells (VSMCs) are important events in the progression of atherosclerosis. Insulin-like growth factor I (IGF-1) possesses both antiapoptotic and mitogenic/motogenic effects in VSMCs although the influence of life cycle on IGF-1-induced effects is unclear. This study was designed to evaluate the effect of IGF-1 on migration, proliferation, and signaling mechanisms in VSMCs from early (3-5) to late (20-22) passages. Migration, proliferation, and cell survival were measured using monolayer wounding, 3 [H]-thymidine incorporation and MTT assay, respectively. Akt and ERK, which are critical to proliferation, differentiation and migration, were examined using Western blot analysis. DCF-DA fluorescence was used to quantify Reactive Oxygen Species (ROS) production. Latepassage VSMCs exhibited significantly higher basal cell proliferation and enhanced sensitivity to IGF-1-stimulated migration compared to cells from early-passages. Phosphorylated Akt and ERK levels were significantly higher in late-passage cells compared to early-passage, which was further enhanced by IGF-1 treatment. Late-passage cells exhibited higher levels of ROS production compared to early-passage, cells. IGF-1 did not significantly alter ROS levels in either passage. Expression of the cell cycle regulator p53, p21, and p16 was not affected by repeated passaging of cells. These results indicated that repeated passaging of VSMCs exhibits a phenotype which has higher proliferative capacity. Activation of trophic signaling molecules such as ERK1/2 and Akt and generation of ROS may represent the mechanisms by which repeated passages of VSMCs acquire a motogenic and mitogenic phenotype.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

et al. 2007

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“…Three collagen isoforms, thrombospondin-4 and insulin-derived growth factor I (IGF-I) were clustered in set 1, defined as extracellular matrix related genes. It was not unexpected to see IGF-I in the same set as collagen because IGF-I up-regulation occurs in patients with hypertrophic cardiomyopathy (25). Furthermore, IGF-I overexpression of fibroblasts plays an important role in tissue remodeling during heart failure.…”

Section: Development and Implication Of Statistical Protocols And A Cmentioning

confidence: 99%

The gene expression fingerprint of human heart failure

Tan

Moravec

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

244

196

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Multiple pathways are responsible for transducing mechanical and hormonal stimuli into changes in gene expression during heart failure. In this study our goals were (i) to develop a sound statistical method to establish a comprehensive cutoff point for identification of differentially expressed genes, (ii) to identify a gene expression fingerprint for heart failure, (iii) to attempt to distinguish different etiologies of heart failure by their gene expression fingerprint, and (iv) to identify gene clusters that show coordinated up-or downregulation in human heart failure. We used oligonucleotide microarrays to profile seven nonfailing (NF) and eight failing (F) human hearts with a diagnosis of end-stage dilated cardiomyopathy. Biological and experimental variability of the hybridization data were analyzed, and then a statistical analysis procedure was developed, including Student's t test after log-transformation and Wilcoxon Mann-Whitney test. A comprehensive cutoff point composed of fold change, average difference, and absolute call was then established and validated by TaqMan PCR. Of 6,606 genes on the GeneChip, 103 genes in 10 functional groups were differentially expressed between F and NF hearts. A dendrogram identified a gene expression fingerprint of F and NF hearts and also distinguished two F hearts with distinct etiologies (familial and alcoholic cardiomyopathy, respectively) with different expression patterns. K means clustering also revealed two potentially novel pathways associated with up-regulation of atrial natriuretic factor and brain natriuretic peptide and with increased expression of extracellular matrix proteins. Gene expression fingerprints may be useful indicators of heart failure etiologies.

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“…The identification of signaling molecules and cascades that could be utilized to improve cardiac function will be critical for the development of new drugs for the treatment of heart failure. Growth hormone and insulinlike growth factor 1 (IGF1) 1 have been considered potential candidates for the treatment of heart failure (2,3). IGFs are produced by many tissues, particularly by the liver in response to growth hormone stimulation.…”

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confidence: 99%

“…Further, it appears that short term administration of IGF1 is beneficial in improving cardiac function in the setting of heart failure (10), and IGF1 transgene expression has been reported to counteract the occurrence of apoptosis in a murine heart failure model (11). However, conflicting results obtained from clinical trials in which IGF1 was chronically administered to humans have questioned the therapeutic value of IGF1 (2,3). Two independent groups have studied the role of IGF1 in the murine heart in vivo using a transgenic approach.…”

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confidence: 99%

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

McMullen

Shioi

Huang

et al. 2004

Journal of Biological Chemistry

374

325

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Insulin-like growth factor 1 (IGF1) was considered a potential candidate for the treatment of heart failure. However, some animal studies and clinical trials have questioned whether elevating IGF1 chronically is beneficial. Secondary effects of increased serum IGF1 levels on other tissues may explain these unfavorable results. The aim of the current study was to examine the role of IGF1 in cardiac myocytes in the absence of secondary effects, and to elucidate downstream signaling pathways and transcriptional regulatory effects of the IGF1 receptor (IGF1R). Transgenic mice overexpressing IGF1R in the heart displayed cardiac hypertrophy, which was the result of an increase in myocyte size, and there was no evidence of histopathology. IGF1R transgenics also displayed enhanced systolic function at 3 months of age, and this was maintained at 12-16 months of age. The phosphoinositide 3-kinase (PI3K)-Aktp70S6K1 pathway was significantly activated in hearts from IGF1R transgenics. Cardiac hypertrophy induced by overexpression of IGF1R was completely blocked by a dominant negative PI3K(p110␣) mutant, suggesting IGF1R promotes compensated cardiac hypertrophy in a PI3K(p110␣)-dependent manner. This study suggests that targeting the cardiac IGF1R-PI3K(p110␣) pathway could be a potential therapeutic strategy for the treatment of heart failure.

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Insulin-like Growth Factor I as aÈCardiac Hormone: Physiological and Pathophysiological Implications in Heart Disease

Cited by 276 publications

References 81 publications

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

The gene expression fingerprint of human heart failure

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

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