Objective Cerebral artosomal dominant arteriopath with subcortical infarcts and leukoencephalopathy(CADASIL) is associated with mutations in the Notch3 gene but the causal mechanisms of the disorder remain unclear. This study explored the effects of Notch3 gene mutations on mitochondrial fusion protein 2,bcl-2 and survivin, which may help to further elucidate the pathophysiological mechanisms of CADASIL.Methods Human aortic vascular smooth muscle cells (HVSMC) were transient transfected with wild-type Notch3, mutation-type Notch3-R90C and empty pcDAN3.1 vector according to the Lipofectamine 2000 method. In order to verify the transfection efficiency, real-time PCR and Western blot were used to detect the expression levels of Notch3. The relative gene expression of survivin and bcl-2 was measured using reverse transcription followed by real-time PCR, and the protein expression level of mfn-2 was also examined by Western blot. Moreover, the rate of apoptosis was detected by fluorescein annexin V-FITC/PI double labeling in the three groups.Results Compared with the other two groups, the expression levels of mfn2 mRNA and protein were significantly higher in the mutation-type group (P<0.05). A significant down-regulation in bcl-2 and survivin mRNA expression levels was also found in the mutation-type group (P<0.05). Moreover, Annexin V/PI double staining assay showed the apoptosis rate significantly increased in the mutation-type group (P<0.05).Conclusions Notch3 gene mutation-mediated up-regulation of mfn2 and down-regulation of bcl-2 and survivin may be an essential pathomechanism of CADASIL.