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Updated: Jan 5, 2026
Studying Left Ventricular Reverse Remodeling by Aortic Debanding in Rodents
Published on: July 14, 2021
[Role of apoptosis signal-regulating kinase 1 in left ventricular remodeling in mice]
Yong-Hua Yuan1, Xiao-Hui Xia, Xue-Hua He
1Department of Pediatric Cardiology, Hunan People's Hospital/First Affiliated Hospital of Hunan Normal University, Changsha 410005, China. he_xh101@163.com.
Objective:
To study the changes and significance of apoptosis signal-regulating kinase 1 (ASK1) in left ventricular remodeling in FVB/N mice.
Methods:
A total of 54 FVB/N mice were randomly divided into 4 groups: 0 d group with 8 mice, 7 d group with 10 mice, 14 d group with 16 mice, and 21 d group with 20 mice. A model of cardiac remodeling was established by intraperitoneal injection of isoproterenol (ISO) at a daily dose of 30 mg/kg, and the 7 d, 14 d, and 21 d groups were injected for 7, 14, and 21 consecutive days respectively. The 0 d group was given intraperitoneal injection of an equal volume of normal saline. Echocardiography was used to measure left ventricular posterior wall thickness at end diastole (dLVPW) and the ratio of heart weight to tibia length (HW/TL) was measured. Hematoxylin-eosin staining was used to measure left ventricular myocardial fiber diameter. Picric-Sirius red staining was used to measure myocardial collagen deposition area in the left ventricle. Quantitative real-time PCR was used to measure the mRNA expression of ASK1, type I collagen (collagen I), and B-type natriuretic peptide (BNP). The mortality rate was observed for each group.
Results:
There were gradual increases in HW/TL, myocardial fiber diameter, and dLVPW after 0, 7, and 14 days of ISO injection (P<0.05). There were no significant changes in HW/TL ratio and dLVPW from days 14 to 21 of ISO injection (P>0.05), while there was a significant reduction in myocardial fiber diameter (P<0.05), which was similar to the value on day 7 (P>0.05). There were significant increases in myocardial collagen deposition area and the mRNA expression of collagen I, ASK1, and BNP after 0, 7, 14, and 21 days of ISO injection, which reached the peaks on day 21 (P<0.01). The mRNA expression of ASK1 was positively correlated with myocardial collagen deposition area and the mRNA expression of collagen I and BNP and had a weak correlation with HW/TL, myocardial fiber diameter, and dLVPW. There was a significant increase in the mortality rate of the mice over the time of ISO injection.
Conclusions:
The expression of ASK1 in the myocardium is closely associated with left ventricular remodeling. The increase of ASK1 expression may lead to the aggravation of left ventricular remodeling, and the mechanism of which needs further study.
Insights
Apoptosis signal-regulating kinase 1 (ASK1) expression increases during cardiac remodeling in mice. Elevated ASK1 correlates with worsening left ventricular remodeling, suggesting a role in disease progression.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cardiac Remodeling Research
Background:
- Left ventricular remodeling is a critical process in heart disease progression.
- Apoptosis signal-regulating kinase 1 (ASK1) is implicated in cellular stress responses.
Purpose of the Study:
- To investigate the role and expression patterns of ASK1 in a mouse model of left ventricular remodeling.
- To understand the correlation between ASK1 and cardiac remodeling markers.
Main Methods:
- Induction of cardiac remodeling in FVB/N mice using isoproterenol (ISO).
- Assessment of cardiac structure and function via echocardiography and histological staining.
- Quantification of mRNA expression for ASK1, collagen I, and BNP using qRT-PCR.
Main Results:
- ISO injection led to progressive increases in heart weight/tibia length, myocardial fiber diameter, and collagen deposition.
- ASK1 mRNA expression significantly increased over time, peaking at day 21.
- ASK1 expression positively correlated with collagen deposition, collagen I, and BNP levels.
Conclusions:
- ASK1 expression is significantly associated with left ventricular remodeling.
- Increased ASK1 may exacerbate left ventricular remodeling, warranting further mechanistic investigation.
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