Molecular basis of cadmium Cardiotoxicity: Chamber-Specific effects of CdO nanoparticles and soluble CdCl₂ exposure

Cadmium, a pervasive xenobiotic, contributes to cardiovascular morbidity and mortality. We investigated the molecular mechanisms of cadmium's impact on the myocardium of various heart chambers. Outbred male rats received 18 intraperitoneal injections of CdCl₂ solution (0.377 mg/kg b.w.) or CdO nanoparticle (Cd_NP) suspension (0.25 mg/kg b.w.) over 6 weeks. Using an in vitro motility assay, we examined the sliding velocity of actin and regulated thin filaments over myosin, the fraction of motile filaments, calcium sensitivity and Hill cooperativity in "pCa-velocity" and "pCa-fraction of motile filaments" relationships, relative force. Using gel electrophoresis, we examined the isoform content of myosin heavy chains (MHC) and light chains (MLC), and MLC 2 phosphorylation. CdCl₂ and Cd_NP exposures similarly reduced atrial myosin kinetics and MLC 2 phosphorylation, despite a 1.7-fold lower dose of Cd_NP. CdCl₂ exposure increased right-ventricular myosin kinetics, shifting MHC isoform content toward α-MHC with higher kinetics. Cd_NP exposure decreased right-ventricular myosin kinetics, shifting MHC isoform content toward β-MHC with lower kinetics. Left-ventricular myosin remained unaffected. Thus, exposure to Cd_NP could exhibit greater cardiotoxicity than CdCl₂, with opposite effects on the right ventricle. Therefore, molecular mechanisms of cadmium's influence on specific heart chambers should be considered when developing strategies for heart disease management.