In NELL-1 deficient mice, blood vessel and heart formation are severely impaired. NELL1 pathway genes are implicated in major cardiovascular disorders and diseases, most notably through the formation of the extracellular matrix (ECM). NELL-1 is expressed primarily in the epicardium and endocardium in fetal and adult hearts, and we have shown that cell death can be overcome in mouse cardiomyocytes deprived of oxygen (hypoxic conditions) and during Acute Myocardial Infarction (AMI). These findings suggest that NELL-1 is a therapeutic agent for proper restoration of cardiac tissue damage.