Impaired IGF-I signalling of hypertrophic hearts in the developmental phase of hypertension in genetically hypertensive rats.
Insulin-like growth factor-I (IGF-I) signalling is reported to contribute to the modulation of blood pressure and set survival and hypertrophic responses in cardiac tissue. However, whether IGF-I signalling normally acts in cardiac tissues of hypertensive rats is unknown. In this study, using spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SPSHR), both with early blood pressure increases, and Wistar-Kyoto (WKY) rats as controls, we measured the hypertrophic and IGF-I signalling activity changes in rat hearts at 4, 6 and 12 weeks of age. Both SHR and SPSHR were found to have significantly increased blood pressures and ratios of heart- and left ventricle- to body weight at 12 weeks of age. However, IGF-IR and its downstream signalling, including the protein levels of PI3K and phosphorylated Akt, known to maintain physiological cardiac hypertrophy and cardiomyocyte survival, were downregulated. The results of dot blotting showed that cardiac mRNA levels of IGF-I in hypertensive rats were higher than those in controls starting from the age of 4 weeks. This difference suggests the increased ligand IGF-I mRNA levels may be a compensatory response caused by the impaired IGF-I signalling. Moreover, enhanced cardiac cytosolic cytochrome-c, a mitochondria-dependent apoptotic pathway component, tended to occur in both hypertensive rats, although it did not reach a significant level. These findings indicate that impaired IGF-IR signalling occurs at early stages, and it may contribute, at least partially, to the development of hypertension and pathological cardiac hypertrophy and to cardiomyocyte apoptosis at later stages in SHR and SPSHR.
Institute of Biochemistry, Chung-Shan Medical University, Taichung, Taiwan.
Wei-Wen
WW
Kuo
Chia-Yih
CY
Chu
Chieh-Hsi
CH
Wu
James A
JA
Lin
Jer-Yuh
JY
Liu
Yi-Hsien
YH
Hsieh
Kwo-Chang
KC
Ueng
Shin-Da
SD
Lee
Dennis Jine-Yuan
DJ
Hsieh
His-Hsien
HH
Hsu
Li-Mien
LM
Chen
Chih-Yang
CY
Huang
D000375:Aging; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology* / Q000503:physiopathology*; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D006352:Heart Ventricles / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D045304:Cytochromes c