Tiny vesicles may reduce vascular remodeling in PH: Rat study
Study points to 'promising therapeutic strategy,' researchers say
Exosomes, a type of small vesicle released by mesenchymal stem cells (MSCs), helped reduce vascular remodeling and ease pulmonary hypertension (PH) symptoms in a rat model of the disease, a study found.
Exosome effects were tied to a modulation of the NF-kB/BMP pathway involved in vascular remodeling, a set of changes in blood vessels’ arrangement and structure that is a hallmark of PH, the study found.
Researchers said they “demonstrated that exosomes derived from human umbilic cord msenchyma stem cells … has a therapeutic effect on pulmonary hypertension via inhibiting pulmonary vascular remodeling.”
The study, “MSC-derived exosomes attenuates pulmonary hypertension via inhibiting pulmonary vascular remodeling,” was published in Experimental Cell Research.
PH is associated with high blood pressure in pulmonary arteries, the blood vessels that supply the lungs, where pulmonary vascular remodeling underlies vascular narrowing or obstruction. Vascular remodeling is marked by the proliferation of smooth muscle cells in the arterial wall.
Cellular communication
Although several treatments can help manage PH symptoms, they do not completely reverse pulmonary vascular remodeling.
MSCs can be obtained from different tissues, including the umbilical cord, fat tissue, or blood. These cells can differentiate into bone, cartilage, muscle, and fat cells, and have anti-inflammatory and anti-scarring properties.
Studies have suggested that exosomes — tiny sacs released by cells that transport protein and nucleic acids, like RNA and DNA, needed for cellular communication — produced by MSCs may help reduce vascular remodeling in PH. However, the underlying molecular mechanisms remain largely unknown.
To learn more, a team from China investigated how exosomes derived from human umbilical cord MSCs reduced pulmonary vascular remodeling in a rat model of PH.
They cultured MSCs in the lab to obtain exosomes, which were then administered to PH rats and compared to controls containing conditioned medium with products secreted by cells.
When exosomes were administered to PH rats, results showed a reduction of pulmonary arterial pressure and an increase of pulmonary artery flow acceleration time, an assessment of the time from the start of blood pumping from the heart’s right ventricle to the peak velocity of pulmonary artery flow.
Administration of MSCs-derived exosomes reduced right ventricle enlargement, as assessed by the right ventricle to left ventricle plus septum (the tissue that separates the right and left ventricles) ratio.
PH rats had greater pulmonary artery wall thickness and area, as well as heart and lung fibrosis (scarring). Exosomes provided benefits in all these measures.
To investigate the molecular mechanisms underlying vascular remodeling, the researchers analyzed the impact of exosomes on pulmonary artery smooth muscle cell growth, which was induced by low oxygen levels. Treatment with MSC exosomes significantly decreased cell growth. No benefits were found with MSCs’ conditioned medium.
The researchers also observed that in both rat and cell models of PH, the levels of NF-kB and BMP proteins were changed with MSC-derived exosomes. NF-kB and BMP signaling are implicated in PH and right ventricular enlargement.
Overall, “this study revealed that the mechanism of [MSC-derived exosomes] attenuates pulmonary hypertension may be related to inhibition of NF-κB signaling to further activation of BMP signaling” and “provided a promising therapeutic strategy for PH vascular remodeling,” the researchers wrote.
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