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|Title:||IGF-2R-Gαq signaling and cardiac hypertrophy in the low-birth-weight lamb|
|Other Titles:||IGF-2R-Galpha q signaling and cardiac hypertrophy in the low-birth-weight lamb|
|Citation:||American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 2015; 308(7):R627-R635|
|Publisher:||American Physiological Society|
|Kimberley C. W. Wang, Darran N. Tosh, Song Zhang, I. Caroline McMillen, Jaime A. Duffield, Doug A. Brooks, and Janna L. Morrison|
|Abstract:||The cardiac insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy in a heterotrimeric G protein receptor-coupled manner involving αq (Gαq) or αs (Gαs). We have previously shown increased left ventricular weight and cardiac IGF-2 and IGF-2R gene expression in low-birth-weight (LBW) compared with average-birth-weight (ABW) lambs. Here, we have investigated the cardiac expression of IGF-2 gene variants, the degree of histone acetylation, and the abundance of proteins in the IGF-2R downstream signaling pathway in ABW and LBW lambs. Samples from the left ventricle of ABW and LBW lambs were collected at 21 days of age. There was increased phospho-CaMKII protein with decreased HDAC 4 abundance in the LBW compared with ABW lambs. There was increased GATA 4 and decreased phospho-troponin I abundance in LBW compared with ABW lambs, which are markers of pathological cardiac hypertrophy and impaired or reduced contractility, respectively. There was increased histone acetylation of H3K9 at IGF-2R promoter and IGF-2R intron 2 differentially methylated region in the LBW lamb. In conclusion, histone acetylation of IGF-2R may lead to increased IGF-2R mRNA expression and subsequently mediate Gαq signaling early in life via CaMKII, resulting in an increased risk of left ventricular hypertrophy and cardiovascular disease in adult life.|
|Keywords:||low birth weight; insulin-like growth factor 2 receptor; histone acetylation|
|Rights:||Copyright © 2015 the American Physiological Society|
|Appears in Collections:||Medicine publications|
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