A hallmark of vascular disease is the cellular adaptive response characterised by proliferation and migration. Although many studies have identified the signalling pathways involved in cell proliferation and migration (p38, p44/42 MAP Kinase and JNK), the mechanisms initiating cell de-differentiation, proliferation/ apoptosis and migration are yet to be fully elucidated.
Mitochondria are one of the organelles that have received growing attention in vascular and pulmonary vascular proliferative disease.1 Mitochondria are classically known to be responsible for cellular energy production. However growing evidence suggests a role in cell de-differentiation and the fine balance between cell apoptosis and proliferation.2
The aim of this work was to expand our understanding of the potential role of mitochondrial and possible influences on vascular proliferative signalling mechanism.
Our initial results confirmed that inhibiting mitochondrial fission process using DRP1 inhibitor MDivi-1 resulted in a significant inhibition of vascular smooth muscle cells proliferation stimulated by both insulin (p < 0.05) and foetal calf serum (p < 0.05).3 Western blot results showed that the phosphorylation of p44/42 was unaffected by MDivi-1 treatment, however, phosphorylation of Akt, cyclin D and 4EBP1 were reduced when the cells were treated with 10μM of MDivi-1. Cell cycle analysis was also conducted and the results showed a concentration dependent cell cycle arrest at G2/M phase (p < 0.05).
These results further support the concept that mitochondria play an important role in vascular smooth muscle cell proliferation independent of the classic pro-mitogenic p44/42 MAPK signalling pathway and highlight a potential role for PI3k-Akt-mTOR-dependent signalling. However, the exact point where mitochondria feature in the mechanistic signalling pathway has yet to be fully elucidated.
Dromparis P, et al. The role of mitochondria in pulmonary vascular remodeling. Journal of molecular medicine (Berlin, Germany) 2010;88:1003–1010
Galluzzi L, et al. Mitochondrial control of cellular life, stress, and death. Circ. Res. 2012;111:1198–1207
Chalmers S, et al. Mitochondrial motility and vascular smooth muscle proliferation. Arterioscler Thromb Vasc Biol 2012;32:3000–3011
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