The purpose of this study was to identify potential OPN targets in biopsies of HF patients, healthy control subjects, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), and to characterize the cardiac phenotype of Col4a3<sup>-/-</sup> mice, relate this to HFpEF, and investigate possible causative roles for OPN in driving the cardiomyopathy.