Fig. 4

HER2 related potential CTRCT mechanisms. The HER2 protein is described as a homodimer from molecular studies. When the Valine amino acid substitutes Isoleucine (HER2 655 Ile/Val SNP) in the transmembrane domain (top left), the HER2 protein assumes a heterozygous configuration, resulting in an excessively stabilized active state [28, 31]. In the presence of HER2 1170 Pro/Ala SNP, the proline amino acid in the carboxy domain (bottom left) has a secondary amide structure that allow more stable hydrogen binding of nearby amino acids [40]. Both changes lead cardiomyocytes to be especially dependent to HER2 signalling, responsible for their growth, survival and performance. In these cases, the blockage of the overactivated HER2 by monoclonal antibodies like trastuzumab, critically reduce the HER2 protective role of cardiomyocytes, making them more susceptible to cellular damage and secondary function alteration