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Updated: May 15, 2026
Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure
Published on: December 2, 2014
Myocardial connective tissue growth factor (CCN2/CTGF) attenuates left ventricular remodeling after myocardial
Jørgen Gravning1, Stein Ørn, Ole Jørgen Kaasbøll
1Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Aims:
Myocardial CCN2/CTGF is induced in heart failure of various etiologies. However, its role in the pathophysiology of left ventricular (LV) remodeling after myocardial infarction (MI) remains unresolved. The current study explores the role of CTGF in infarct healing and LV remodeling in an animal model and in patients admitted for acute ST-elevation MI.
Methods And Results:
Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) and non-transgenic littermate controls (NLC) were subjected to permanent ligation of the left anterior descending coronary artery. Despite similar infarct size (area of infarction relative to area at risk) 24 hours after ligation of the coronary artery in Tg-CTGF and NLC mice, Tg-CTGF mice disclosed smaller area of scar tissue, smaller increase of cardiac hypertrophy, and less LV dilatation and deterioration of LV function 4 weeks after MI. Tg-CTGF mice also revealed substantially reduced mortality after MI. Remote/peri-infarct tissue of Tg-CTGF mice contained reduced numbers of leucocytes, macrophages, and cells undergoing apoptosis as compared with NLC mice. In a cohort of patients with acute ST-elevation MI (n = 42) admitted to hospital for percutaneous coronary intervention (PCI) serum-CTGF levels (s-CTGF) were monitored and related to infarct size and LV function assessed by cardiac MRI. Increase in s-CTGF levels after MI was associated with reduced infarct size and improved LV ejection fraction one year after MI, as well as attenuated levels of CRP and GDF-15.
Conclusion:
Increased myocardial CTGF activities after MI are associated with attenuation of LV remodeling and improved LV function mediated by attenuation of inflammatory responses and inhibition of apoptosis.
Insights
Cardiac Connective Tissue Growth Factor (CTGF) reduces adverse cardiac remodeling and improves heart function after myocardial infarction (MI). This study shows CTGF attenuates inflammation and apoptosis, leading to better outcomes in mice and humans.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Regenerative Medicine
Background:
- Connective Tissue Growth Factor (CTGF) is upregulated in heart failure.
- The specific role of CTGF in myocardial infarction (MI) and subsequent left ventricular (LV) remodeling is not fully understood.
Purpose of the Study:
- To investigate the role of CTGF in infarct healing and LV remodeling post-MI.
- To explore CTGF's impact on cardiac function and survival in a mouse model and human patients.
Main Methods:
- Utilized transgenic mice overexpressing cardiac CTGF and subjected them to coronary artery ligation.
- Assessed infarct size, cardiac hypertrophy, LV dilatation, LV function, and mortality.
- Monitored serum CTGF levels in ST-elevation MI patients undergoing PCI, correlating with cardiac MRI findings.
Main Results:
- Overexpression of CTGF in mice led to smaller scar tissue, reduced hypertrophy, less LV dilatation, and improved LV function 4 weeks post-MI.
- Tg-CTGF mice exhibited significantly lower mortality rates after MI.
- In patients, increased serum CTGF post-MI correlated with reduced infarct size, improved LV ejection fraction, and lower inflammatory markers (CRP, GDF-15).
Conclusions:
- Elevated myocardial CTGF activity post-MI is linked to attenuated LV remodeling and enhanced LV function.
- These beneficial effects appear to be mediated by reduced inflammatory responses and inhibition of apoptosis.
- CTGF shows potential as a therapeutic target for improving outcomes after myocardial infarction.
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