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Updated: Dec 7, 2025
Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
Published on: February 12, 2021
lncRNA ZEB2-AS1 stimulates cardiac hypertrophy by downregulating PTEN
Zhi Cheng1, Lingyun Liu1, Qingguo Li1
1Cardiovascular Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003, P.R. China.
Insights
Long non-coding RNA ZEB2-AS1 promotes cardiac hypertrophy (CH) by downregulating PTEN. This study reveals ZEB2-AS1 as a potential therapeutic target for cardiovascular diseases like heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Non-coding RNA Research
Background:
- Cardiac hypertrophy (CH) is a significant risk factor for heart failure and sudden cardiac death.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cardiovascular pathophysiology.
- The specific role of lncRNA ZEB2 antisense RNA 1 (ZEB2-AS1) in CH remains largely unexplored.
Purpose of the Study:
- To investigate the function of lncRNA ZEB2-AS1 in regulating cardiomyocyte hypertrophy.
- To elucidate the underlying molecular mechanism involving ZEB2-AS1 in cardiac hypertrophy.
- To explore the relationship between ZEB2-AS1 and phosphatase and tensin homolog (PTEN) in the context of CH.
Main Methods:
- Establishment of both in vivo (transverse aortic constriction) and in vitro (phenylephrine treatment of cardiomyocytes) cardiac hypertrophy models.
- Quantification of ZEB2-AS1, natriuretic peptide A (ANP), brain natriuretic peptide (BNP), and PTEN expression using western blotting and other techniques.
- Assessment of ZEB2-AS1 knockdown and PTEN overexpression effects on hypertrophic cardiomyocyte characteristics.
Main Results:
- ZEB2-AS1, ANP, and BNP expression were significantly upregulated in both in vivo and in vitro CH models.
- Knockdown of ZEB2-AS1 reduced cardiomyocyte surface area and downregulated ANP and BNP expression.
- Overexpression of PTEN mimicked these effects and reversed the impact of ZEB2-AS1 on hypertrophic cells.
Conclusions:
- lncRNA ZEB2-AS1 plays a crucial role in promoting cardiac hypertrophy.
- ZEB2-AS1 appears to exert its pro-hypertrophic effects by downregulating PTEN expression.
- ZEB2-AS1 represents a potential therapeutic target for managing cardiac hypertrophy and associated cardiovascular diseases.
Abstract:
Cardiac hypertrophy (CH) is closely related to a range of cardiovascular diseases, including heart failure and sudden cardiac death. The present study aimed to elucidate the role of long non-coding RNA (lncRNA) ZEB2 antisense RNA 1 (ZEB2-AS1) in regulating the hypertrophic process of cardiomyocytes and the potential underlying mechanism. An in vivo CH mouse model was established by performing transverse aortic constriction procedures. An in vitro CH model was established in primary cardiomyocytes isolated from mice by phenylephrine (PE) treatment. The relative protein levels of BNP, ANP and PTEN in cells with different groups (CH group and control group) were determined by western blotting. Relative expression levels of ZEB2-AS1, natriuretic peptide A (ANP) and brain natriuretic peptide (BNP) were determined in both in vivo and in vitro CH models. The regulatory effects of ZEB2-AS1/phosphatase and tensin homolog (PTEN) on cell surface area, and the relative expression levels of ANP and BNP were explored. ZEB2-AS1, ANP and BNP expression levels were increased in both in vivo and in vitro CH models compared with the sham and negative control groups, respectively. ZEB2-AS1 knockdown decreased cell surface area, and downregulated ANP and BNP expression levels in PE-treated primary cardiomyocytes. Similarly, PTEN overexpression reduced cell surface area, and downregulated ANP and BNP expression levels in PE-treated primary cardiomyocytes. Moreover, PTEN reversed the regulatory effects of ZEB2-AS1 on hypertrophic cardiomyocytes. Therefore, the present study suggested that lncRNA ZEB2-AS1 may influence the progression of CH by downregulating PTEN.
