Mitochondria transfer ameliorates disturbed flow-induced proatherogenic effects through metabolic reprogramming in human endothelial cells

李昀臻、趙曼甯

Abstract

Mitochondria dysfunction induced by disturbed blood flow at arterial bifurcations make endothelial cells disorder and develop atherosclerosis. Our results revealed that mitochondria transfer ameliorated endothelial dysfunction of respiratory chain caused by disturbed flow. Our study shed a light on the potential of mitochondria transfer as a novel therapy for atherosclerosis.

Research Purpose

Examine whether mitochondria transfer could ameliorate deleterious effects of disturbed flow in human aortic endothelial cells.

Methodology

1. ECs were exposed to atherorelevant flow generated by a cone-plate flow device, and the flow type was called disturbed flow, compared to the unidirectional flow.
2. Atherosclerosis-associated genes and protein were quantified to support that proatherogenic effect was induced by the disturbed flow made by cone-plate flow device.
2. Mitochondria health of unidirectional flow cells and disturbed flow cells were examined on inner membrane potential and aerobic respiration rate.
3. UF cells’ mitochondria were transferred into DF cells.

Conclusions and Future Work

• Pro-atherogenic effects were induced in DF cells via the cone plate flow system, supported by the up-regulated atherogenic gene and protein expression.
• Mitochondria in UF cells were healthier, supported by better inner membrane potential, higher basal respiration rate and higher maximal respiration rate.
• Mito-transplanted DF cells has enhanced oxygen consumption rate to the UF cells side, indicates that mitochondria transplantation can restore DF cells in oxygen consumption rate, but not completely.