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. 2022 Jul 18;23(14):7916. doi: 10.3390/ijms23147916

Figure 1.

Figure 1

The regulatory mechanisms of vascular smooth muscle cell migration and proliferation. Potential up- and down-regulatory mechanisms of vascular smooth muscle cell migration (VSMC) involving both CaMKII-dependent and -independent mechanisms at both transcriptional and post-transcriptional levels. CaMKIIγ expression and activation leads to promotion of VSMC proliferation and migration, both directly and indirectly, through p21 and p53 cell cycle inhibitors. CaMKIIδ expression leads to increased VSMC migration and proliferation. PKCδ and PDGF both upregulate CaMKIIδ to increase VSMC migration and proliferation. PKCδ works by upregulating ERK1/2 activity via ATP, leading to increased CaMKIIδ activity. PDGF acts directly and indirectly via ERK1/2 to upregulate CaMKIIδ, leading to VSMC migration and proliferation. MCU expression is upregulated by MICU1 and EMRE, leading to the promotion of VMSC migration and proliferation. MMP-9 is upregulated by CaMKIIδ and ERK1/2, leading to increased VSMC migration and proliferation, while eNOS downregulates MMP-9. eNOS further downregulates MMP-2 and upregulates the tissue inhibitor of metalloproteinases 2 (TIMP2) to decrease VSMC migration and proliferation.