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Mouse Model of Coronary Collateral Growth Through Repetitive Ischemia
Molly Enrick1, James Gadd1, Katie Yanez2
1Department of Integrative Medical Sciences, Northeast Ohio Medical University.
Insights
Researchers developed a new mouse model for studying coronary collateral growth (CCG), a natural bypass for ischemic heart disease. This model uses repetitive ischemia to induce CCG, enabling further research into this vital process.
Area of Science:
- Cardiovascular Biology
- Ischemic Heart Disease Research
- Animal Models in Cardiology
Background:
- Coronary collaterals act as natural bypasses in ischemic heart diseases (IHD).
- Coronary collateral growth (CCG) is a potential therapeutic target for IHD, especially in patients with impaired CCG due to type 2 diabetes or metabolic syndrome.
- The lack of suitable mouse models has hindered the study of CCG mechanisms.
Purpose of the Study:
- To develop a novel mouse model for investigating coronary collateral growth (CCG).
- To facilitate genetic manipulation studies for understanding CCG pathways and cell types.
- To advance therapeutic strategies for ischemic heart disease.
Main Methods:
- Development of a mouse model of CCG induced by repetitive ischemia (RI).
- Surgical implantation of a pneumatic occluder on the left anterior descending artery (LAD).
- Utilizing an automated pressure-based inflation system for precise control of RI protocol.
Main Results:
- Successfully established a reproducible mouse model for inducing CCG via repetitive ischemia.
- The developed model has been used to demonstrate that sprouting angiogenesis underlies CCG in adult mouse hearts.
- This model allows for detailed mechanistic studies of CCG, including pathway and cell-type identification.
Conclusions:
- The novel mouse model provides a valuable platform for studying coronary collateral growth.
- This research opens avenues for developing new therapies targeting CCG in ischemic heart disease.
- Understanding CCG mechanisms in mice can translate to improved treatments for human cardiovascular conditions.
Abstract:
Coronary collaterals are a natural bypass in ischemic heart diseases (IHD), and so for many years, coronary collateral growth (CCG) has been a promising therapeutic target for IHD, particularly in patients with type 2 diabetes or metabolic syndrome in which CCG is impaired. However, this process is understudied, partly due to the lack of mouse models of CCG, even though other animal models, such as pigs, dogs, and rats, have been established. A mouse model can take advantage of the many genetic modifications available for the species, including lineage tracing and gene regulation (overexpression or knockout), to elucidate the process and mechanism of CCG, including the pathways and cell types involved. We, therefore, set out to develop a mouse model of CCG induced by repetitive ischemia (RI) via transient, repetitive occlusion of the left anterior descending artery (LAD). This manuscript provides details of this mouse CCG model, including the RI surgery to implant a pneumatic occluder on the LAD, the automated pressure-based inflation system used for controlling the pressure and timing of inflation, and the sequence of the RI protocol. This method has already generated one publication to elucidate the process of CCG induced by RI, showing that sprouting angiogenesis gives rise to mature coronary arteries in CCG in adult mouse hearts.
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