Inhibition of HSF2 SUMOylation via MEL18 upregulates IGF-IIR and leads to hypertension-induced cardiac hypertrophy. (15th April 2018)

• Record Type: Journal Article
• Authors: Huang, Chih-Yang; Kuo, Chia-Hua; Pai, Pei-Ying; Ho, Tsung-Jung; Lin, Yueh-Min; Chen, Ray-Jade; Tsai, Fuu-Jen; Vijaya Padma, V.; Kuo, Wei-Wen; Huang, Chih-Yang
• Is Part Of: International journal of cardiology. Volume 257(2018)
• Page Start: 283
• Page End: 290
• Publication Date: 2018-04-15
• Subjects: ANP atrial natriuretic protein -- ANG II angiotensin II -- ARB angiotensin II receptor type I blocker -- BNP brain natriuretic protein -- HSF2 heat shock transcription factor 2 -- IGF-IIR insulin-like growth factor receptor II -- NRVM neonatal rat ventricular myocyte -- SHR spontaneously hypertensive rats -- SUMO-1 small ubiquitin-like modifier-1 -- SUMOylation small ubiquitin-like modification -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling; HSF2 -- ANGII -- IGF-IIR -- SUMOylation -- Hypertension -- MEL18; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2017.10.102
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Cardiac hypertrophy is a major characteristic of early-stage hypertension-related heart failure. We have found that the insulin-like growth factor receptor II (IGF-IIR) signaling was critical for hypertensive angiotensin II-induced cardiomyocyte hypertrophy and apoptosis. Moreover, this IGF-IIR signaling was elegantly modulated by the heat shock transcription factors (HSFs) during heart failure. However, the detailed mechanism by which HSFs regulates IGF-IIR during hypertension-induced cardiac hypertrophy remains elusive. In this study, we found that heat shock transcription factor 2 (HSF2) activated IGF-IIR to induce cardiac hypertrophy for hypertension-induced heart failure. The transcriptional activity of HSF2 appeared to be primarily mediated by SUMOylation via conjugation with small ubiquitin-like modifier-1 (SUMO-1). The SUMOylation of HSF2 was severely attenuated by MEL18 (also known as polycomb group ring finger 2 or PCGF2) in the heart of spontaneously hypertensive rats (SHR). Inhibition of HSF2 SUMOylation severely induced cardiac hypertrophy via IGF-IIR-mediated signaling in hypertensive rats. Angiotensin II receptor type I blocker (ARB) treatment in spontaneously hypertensive rats restored HSF2 SUMOylation and alleviated the cardiac defects. Thus, our study uncovered a novel MEL18-SUMO-1-HSF2-IGF-IIR pathway in the heart that profoundly influences cardiac hypertrophy for hypertension-induced heart failure.