RGS7 knockdown protects VCM from EC-driven myocyte dysfunction. (A) RGS7 expression in heart, VCM, VCF, and EC. (B) VCM and EC were treated with conditioned media from doxorubicin-treated (3 μM, 24 h) EC or VCM, respectively. Lysates were probed for RGS7 expression (n = 3). (C) Control or RGS7 KD VCM cultures (n = 3) were treated with conditioned media from doxorubicin-treated (3 μM, 24 h) EC and the resultant lysates were probed for RGS7, p-CaMKII, ox-CaMKII, iNOS, NRG1, and p-AKT. (D) Control or RGS7 KO AC-16 cardiomyocytes (n = 3) were treated with conditioned media from doxorubicin-treated (3 μM, 24 h) HUVEC cells, and immunoblotting was performed to detect RGS7, p-CaMKII, ox-CaMKII, iNOS, NRG1, and 4-HNE. (E) Murine ECs (n = 3) were treated with doxorubicin (3 μM, 24 h), and the culture media transplanted onto VCM cultures in the presence or absence of the tyrosine kinase inhibitor cl-1033 (2 μM, 1 h). RGS7, ox-CaMKII, and CaMKII expression were determined.