The alternate possibility of mechanism for the pathogenesis was the structural weakness of the lamina, which might be a predisposing factor to induce nuclear damage and apoptosis. In the lamin A/C knockout mice, the myocyte Zelboraf 918504-65-1 apoptosis was observed by 2-fold higher than that of in NTG animals, but we found that the level of apoptosis was 8.5-fold higher in the LmnaE82K transgenic mice than that of the NTG mice. We concluded that LMNA E82K mutation in mice, and probably in humans, disrupted integrity and triggered apoptosis and finally resulted in DCM and heart failure. It was possible that specialized properties of conduction system myocytes made these more susceptible than surrounding myocytes to pro-apoptotic signals triggered by mutated LMNA, and the transgenic mice may developed the conduction defects. Our most interesting finding was that the expression of LMNA E82K in heart tissues increased the expression of FAS, accompanied with the activation of caspase-8 and caspase-3 in LmnaE82K transgenic mice. The release of cytochrome c from mitochondria to cytosol was also induced by the expression of LMNA E82K, followed the activation of caspase-9. FAS, as a member of the death receptor superfamily, plays a central role in the death receptor pathway. After FAS ligand binding, FAS receptors undergo trimerization and recruit FASassociated death domain. FAS/FADD complex binds to the initiator caspase-8. According to the cell type, activated caspase-8 may propagate the apoptotic signal either through a direct activation of executioner downstream caspases or via the release of cytochrome c from mitochondria. The involvement of mitochondria in apoptotic processes has already been clearly demonstrated, that the release of cytochrome c triggers the assembly of Apoptotic protease-activating factor and procaspase-9 to form an apoptosome, and procaspase-9 is then autolyticaly cleaved to active caspase-9, which then activates procaspase-3 to active caspase resulting in cleavage of its substrates and apoptosis. Loss of myocytes is a feature of the cardiomyopathic process that contributes to progressive decline in LV function and congestive heart failure. Although a number of stimuli appear to trigger the process of apoptosis in cardiomyocyte. Our results indicated that the two major signaling pathways of apoptosis: the death receptor pathway and the mitochondrial pathway were activated by the expression of LMNA E82K in heart tissue. It has been indicated that lamin A/C regulates Wnt/b-catenin and MAPK signal pathway, and it also regulates a certain numbers of growth factors and transcription factors, like TGF-b and c-Fos, which regulates differentiation, proliferation and apoptosis in many cell types. The LMNA mutations have been shown to be the severity of the cardiac symptoms, which may cause in diverse mechanisms. The apoptosis, at least for the LMNA E82K or the mutations in the rod region of Lamin A/C, might be an important mechanism causing continuous loss of myocytes.