SMAD2 and ischemia reperfusion injury: Increased myocardial expression of CCN2 has been demonstrated to confer cardio-protection by protecting the heart from ischemia-reperfusion injury via GSK-3ß pathway inhibition, phospho-SMAD2 activation, and gene expression reprogramming [92]; moreover, in a model of acute cardiomyopathy, transgenic mice with cardiomyocyte-specific CTGF overexpression displayed preserved cardiac function compared to wild-type control rats that exhibited significantly reduced systolic function [93].