Cardiac cryoinjury in leopard geckos induced a 6-fold increase in cardiomyocyte proliferation in injury-adjacent regions at 3 days post-injury, leading to near-complete myocardial regeneration by 100 days.
Leopard geckos are capable of near-complete structural and functional heart regeneration following severe cryoinjury, demonstrating that cardiac regenerative capacity is conserved in some reptiles.
Effect estimate: 6-fold increase
p-value: p=<0.0001
Among mammals, injury to the heart typically results in scar formation and diminished cardiovascular function. In contrast, some teleost fish and salamanders can replace damaged heart tissue and restore overall function. For most species, however, less is known. Here, we investigate cardiac self-repair in an amniote capable of multi-tissue regeneration, the leopard gecko (Eublepharis macularius). To create a heart lesion, we placed a liquid nitrogen-cooled metal probe directly onto the ventricle. The result was a cryoinjury to ~20% of the ventricle. Cardiac cryoinjury induced localized cardiac cell death, followed by an increase in cell proliferation by injury-adjacent cardiomyocytes and non-cardiomyocytes. By 100 days, the histology of the ventricular myocardium was nearly completely restored. Echocardiography and invasive hemodynamic monitoring demonstrated that global cardiac function is restored within this timeframe, verifying functional replacement of the myocardium. To explore the molecular basis, we performed bulk RNA sequencing of the injury-adjacent tissue and found that many of the molecular mechanisms common to other cardiac regenerating species, including genes involved in heart development, glycolysis, and extracellular matrix deposition, are also conserved in geckos. Taken together, this work expands the comparative framework of heart regeneration to include reptiles and indicates that the ability to replace missing or damaged cardiomyocytes is shared across >50 million years of evolution.
Jacyniak et al. (Wed,) conducted a other in Cardiac cryoinjury (n=32). Cardiac cryoinjury vs. Sham surgery / Injury-distant regions was evaluated on Cardiomyocyte proliferation in injury-adjacent vs injury-distant regions at 3 days post-cryoinjury (6-fold increase, p=<0.0001). Cardiac cryoinjury in leopard geckos induced a 6-fold increase in cardiomyocyte proliferation in injury-adjacent regions at 3 days post-injury, leading to near-complete myocardial regeneration by 100 days.