Search

Hexarelin is a synthetic growth hormone-releasing peptide that exerts cardioprotective effects. Regulation of autophagy is known to be cardioprotective so this study examined the role of autophagy and potential regulatory mechanisms in hexarelin-elicited anti-cardiac hypertrophic action in cardiomyocytes subjected to hypertrophy. H9C2 cardiomyocytes were subjected to hypertrophy by angiotensin-II (Ang-II). Autophagic light chain-3 (LC3) and cytoskeletal proteins were determined by immunofluorescence assay. Autophagy was also detected using monodansylcadaverine (MDC) for autophagic vacuole visualization and Cyto-ID staining for autophagic flux measurement. Molecular changes were analysed by Western blotting and qRT-PCR. Apoptosis was evaluated using flow cytometry and TUNEL assay. ATP content and CCK-8 assay were used in assessing enhanced cell survival whilst oxidative stress was analysed by measuring malondialdehyde(MDA) and superoxide dismutase(SOD) levels. Ang-II induced cardiomyocyte hypertrophy, oxidative stress, apoptosis and decreased cell survival, all of which were significantly suppressed by hexarelin treatment which also enhanced autophagy in hypertrophic H9C2 cells. Furthermore, inhibition of hexarelin induced autophagy by 3-methyladenine (3MA) abolished the anti-hypertrophic function of hexarelin and also abrogated the protection of hexarelin against cell survival inhibition and apoptosis. Conversely, the application of autophagy stimulator rapamycin in H9C2 hypertrophic cells inhibited apoptosis, cell survival and reduced cell size as well. Additionally, hexarelin regulated the upstream signalling of autophagy by inhibiting the phosphorylation of mammalian target of rapamycin(mTOR). We propose that hexarelin plays a novel role of attenuating cardiomyocyte hypertrophy and apoptosisviaan autophagy-dependent mechanism associated with the suppression of the mTOR signalling pathway.

This review focuses on the current and past state of understanding with regards to the function of PTEN gene in signalling pathways in chronic heart failure and cardiac hypertrophy and explores how PTEN signalling is modified in the same. The role of PTEN in both pathological and physiological cardiac hypertrophy and how regulation and dysregulation contribute to chronic heart failures and cardiac hypertrophy are also discussed. The modulation of transduction pathway by PTEN with regards to cardiac remodelling, hypertrophy, phenotypic modulation, and apoptosis in both healthy and hypertrophic hearts are talked over. Targeted regulation of PTEN gene in signal transduction pathway forms the basis of development of new PTEN modifying therapies for use in chronic heart failures and related cardiovascular diseases. Signalling pathways are implicated in both pathological and physiological cardiac hypertrophy. These signals involve various protein kinases and activation or inactivation of specific genes that have a role in cardiomyocyte proliferation and apoptosis.