Mitochondria Transplants Ease Hypoxia-induced Pulmonary Hypertension in Animal Study

Mitochondrial transplants may prevent or ease hypoxia-induced pulmonary hypertension, according to a study developed at Huazhong University of Science and Technology in China.

The study, “Mitochondrial transplantation attenuates hypoxic pulmonary hypertension,” published in the journal Oncotarget, took advantage of the different mitochondrial responses to hypoxia (low oxygen levels) in distinct cell types.

Although hypoxia exposure can induce pulmonary hypertension by triggering vasoconstriction and vascular remodeling in the pulmonary arteries, it leads to vascular relaxation in systemic arteries, such as the femoral artery. In a recent study, the authors revealed that hypoxia’s paradoxical effect was controlled by mitochondrial heterogeneity in the muscle cells that surround the different arteries. In fact, transplanting mitochondria from the muscle cells surrounding the pulmonary artery to those surrounding the femoral artery in vitro markedly changed the cell’s response to hypoxia.

Investigators now aimed to explore whether such mitochondria heterogeneity could be used to treat or prevent hypoxia-induced hypertension in vivo.

The team isolated mitochondria from femoral artery smooth muscle cells and injected them in the bloodstream of hypoxia-exposed rats. The mitochondria were labeled with a fluorescent dye, allowing them to be tracked and their distribution in the body examined.

Researchers found that the mitochondria were present in the lung tissues, particularly in pulmonary artery smooth muscle cells, but not in the kidney, liver, or spleen, most likely because these organs cannot take up particles with the size of the mitochondria.

Results revealed that rats injected with femoral artery mitochondria had a significantly lower hypoxia-induced pulmonary vasoconstriction, pulmonary artery resistance, and vascular remodeling compared to control rats. Importantly, these effects were observed when the mitochondria were injected either during or after hypoxia exposure. Conversely, injecting mitochondria isolated from the pulmonary artery smooth muscle cells slightly augmented hypoxia-induced pulmonary hypertension.

Although the exact mechanisms through which mitochondria transplantation change the responses to hypoxia are not clear, the effectiveness of this approach before and after the establishment of hypoxia-induced pulmonary hypertension in rats is promising, and may lead to the development of effective therapeutic approaches in patients with the condition, which so far remains incurable.

“Mitochondria dysfunction is widely involved in pathophysiological processes of diseases in a variety of cells, tissues and organs,” the researchers wrote. “It becomes interesting to reveal whether mitochondria transplantation is generally applicable in other organs or tissues and whether it is a valuable approach for the treatment and or prevention of other diseases in experimental models.”