Related Experiment Video
Updated: May 12, 2026
Improved Generation of Induced Cardiomyocytes Using a Polycistronic Construct Expressing Optimal Ratio of Gata4, Mef2c and Tbx5
Published on: November 13, 2015
Function and expression of ATIP and its variants in cardiomyoblast cell line H9c2
Naghmeh Varghayee1, Michael A Krezel1, Linda Rezmann1
1Clinical Pharmacology and Therapeutics Unit, Department of Medicine, University of Melbourne, Austin Health, Australia.
Hypothesis:
Cardiac hypertrophy in myocytes is in part regulated by changes in expression of a novel Ang II type 2 receptor (AT2-receptor) interacting protein identified as ATIP.
Introduction:
The role of the AT2-receptor in cardiac hypertrophy is controversial, with some reports indicating that AT2-receptor activation has detrimental effects on disease progression, whereas others indicate that it has a beneficial role.
Materials And Methods:
In an effort to unravel this paradox, we examined the expression and function of ATIP in cell-based models of cardiac hypertrophy using QPCR, immunohistochemistry, cell proliferation, morphological and transfection techniques in H9c2 cardio-myoblast and myotubules.
Results:
These studies indicate that in cultured cardio-myoblast and myotubules, Ang II mediates cellular hypertrophy and proliferation solely via the AT1-receptor, the ATIP variants are abundantly expressed and that ATIP3 may play an anti-proliferative/hypertrophic role in these cells in the absence of AT2-receptor expression or activation.
Conclusions:
Previously ATIP has been shown to inhibit growth factor signalling in cancerous cells via an interaction with the AT2-receptor. This is the first report to identify that ATIP may have a similar role in other disease states characterised by excessive growth and indicates that for ATIP3, at least, an interaction with the AT2-receptor may not be necessary.
Insights
This study reveals that ATIP3 may inhibit cardiac hypertrophy and proliferation in myocytes, independent of the Ang II type 2 receptor (AT2-receptor). ATIP3
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Cellular Signaling
Background:
- The role of the Angiotensin II type 2 receptor (AT2-receptor) in cardiac hypertrophy remains controversial.
- Conflicting reports exist regarding the beneficial or detrimental effects of AT2-receptor activation in cardiac disease progression.
Purpose of the Study:
- To investigate the expression and function of the novel Ang II type 2 receptor (AT2-receptor) interacting protein (ATIP) in cardiac hypertrophy.
- To elucidate the role of ATIP variants, particularly ATIP3, in regulating myocyte growth and proliferation.
Main Methods:
- Utilized cell-based models of cardiac hypertrophy (H9c2 cardio-myoblasts and myotubules).
- Employed quantitative PCR (QPCR), immunohistochemistry, cell proliferation assays, morphological analysis, and transfection techniques.
- Examined the influence of Angiotensin II (Ang II) signaling pathways.
Main Results:
- Angiotensin II (Ang II) mediates cardiac hypertrophy and proliferation exclusively through the AT1-receptor in cultured cells.
- Abundant expression of ATIP variants was observed in these cardiac cells.
- ATIP3 demonstrated a potential anti-proliferative and anti-hypertrophic role, even without AT2-receptor activation.
Conclusions:
- ATIP, previously known to inhibit growth factor signaling in cancer cells via AT2-receptor interaction, may play a similar role in other excessive growth conditions.
- This study is the first to suggest that ATIP3's role in disease states characterized by excessive growth may not necessitate interaction with the AT2-receptor.
