Related Experiment Video
Updated: Jun 19, 2026
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
Regulation of Clusterin in the Heart and Plasma of Mice After Transverse Aortic Constriction
Annie Turkieh1, Lukas Weber2, Maggy Chwastyniak1
1Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE, Université de Lille, Lille, France.
Insights
Clusterin (CLU) expression increases in the heart during pressure overload, correlating with cardiac remodelling. However, plasma CLU levels do not effectively indicate this adverse cardiac remodelling or heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Biomarker Discovery
Background:
- Chronic pressure overload causes adverse cardiac remodelling, leading to heart failure (HF).
- Identifying novel biomarkers is crucial for understanding and preventing HF.
- Clusterin (CLU) was previously identified as a biomarker for cardiac remodelling post-myocardial infarction.
Purpose of the Study:
- To investigate CLU expression regulation in the heart under pressure overload.
- To determine if CLU can serve as an indicator of adverse cardiac remodelling due to pressure overload.
Main Methods:
- Quantification of CLU mRNA and mature protein (m-CLU) in mouse left ventricles (LV) after transverse aortic constriction (TAC).
- Correlation analysis of CLU levels with cardiac hypertrophy and fibrosis gene markers.
- Assessment of correlations between m-CLU and LV structural and functional parameters.
Main Results:
- TAC induced increased CLU mRNA and m-CLU protein in the LV.
- Cardiac CLU mRNA correlated positively with pro-hypertrophic and pro-/anti-fibrotic genes.
- Increased m-CLU levels were associated with LV hypertrophy, dilation, and reduced ejection fraction in severe cases.
- Plasma CLU levels showed no significant difference between TAC and sham groups.
Conclusions:
- Cardiac CLU expression is upregulated in the LV during pressure overload-induced adverse cardiac remodelling.
- Cardiac m-CLU is a potential indicator of cardiac remodelling and dysfunction.
- Plasma CLU is not a reliable biomarker for pressure overload-induced cardiac remodelling and dysfunction.
Abstract:
Chronic pressure overload induces adverse cardiac remodelling characterised by left ventricular (LV) hypertrophy and fibrosis, leading to heart failure (HF). Identification of new biomarkers for adverse cardiac remodelling enables us to better understand this process and, consequently, to prevent HF. We recently identified clusterin (CLU) as a biomarker of cardiac remodelling and HF after myocardial infarction. The aim of this study was to investigate whether CLU expression is regulated in the heart and could be used as an indicator of adverse cardiac remodelling in response to pressure overload. We quantified CLU in the LV of mice subjected to transverse aortic constriction (TAC) and observed increased CLU mRNA levels and its mature protein form (m-CLU) compared to the sham. Interestingly, CLU mRNA levels were positively correlated with pro-hypertrophic (ANP, BNP, B-MHC), pro- and anti-fibrotic (TGFb, ColI and CILP) genes. In addition, m-CLU was positively correlated with LV hypertrophy, LV end diastolic and systolic diameters, and negatively correlated with LV ejection fraction. Finally, we observed that m-CLU levels only increased in TAC mice with severe cardiac remodelling and dysfunction without any significant difference in plasma CLU levels. This is the first study to demonstrate that cardiac expression of CLU is induced in the LV of TAC mice during adverse cardiac remodelling. However, plasma CLU levels could not be used as biomarkers of TAC-induced cardiac remodelling and dysfunction.
