Mouse Model of Coronary Collateral Growth Through Repetitive Ischemia

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.