Apelin delivered to damaged lungs eases PAH in rats, mice: Study
Researchers use small particles to bring peptide to blood vessels
Researchers used small particles called extracellular vesicles to deliver a form of apelin directly to damaged blood vessels in the lungs, which helped reverse the damage and improve heart function in animal models of pulmonary arterial hypertension (PAH), according to a study.
Apelin, a peptide that plays a role in restoring cardiovascular function, was bound by researchers to a stretch of protein building blocks called CAR to guide it to damaged blood vessels. CAR targets heparan sulfate, a sugar molecule found in high amounts on the surface of endothelial cells lining blood vessels affected by PAH.
“Our findings establish CAR-Apelin [extracellular vesicles] as a transformative therapeutic strategy, providing a targeted and effective approach to meet critical unmet needs in PAH treatment,” wrote a team led by researchers in South Korea.
These findings are described in the study “Targeted delivery of apelin using a novel extracellular vesicle platform for pulmonary arterial hypertension treatment,” which was published in the journal Biomaterials.
PAH-targeted delivery shows promise
In PAH, the pulmonary arteries that take blood from the right side of the heart to the lungs narrow, increasing blood pressure. This makes it hard for the right side of the heart to pump enough blood through to the lungs, leading to symptoms such as shortness of breath. Left untreated, it can lead to heart failure.
One potential treatment involves apelin peptides, short chains of protein building blocks called amino acids that maintain healthy blood vessels and block the proliferation, or multiplication, of smooth muscle cells that narrow pulmonary blood vessels. However, using apelin as a medication has proven difficult because it shows poor selectivity for lung blood vessels.
To get around limitations, the researchers developed a delivery system using extracellular vesicles, naturally occurring particles that cells release to send molecules to each other. These extracellular vesicles were engineered to carry apelin-13, the most biologically active isoform of apelin, according to the scientists, directly to damaged blood vessels in the lungs, where it is needed most.
To do this, they used a protein called IFITM3 to position the apelin on the surface of the extracellular vesicles in a way that kept it active and able to interact properly with its receptor protein. They also bound it to CAR to ensure that the extracellular vesicles delivered apelin precisely to damaged blood vessels.
When injected directly into the bloodstream of rats mimicking symptoms of PAH, CAR-Apelin extracellular vesicles achieved superior accumulation in PAH-affected lung tissues relative to control extracellular vesicles, “highlighting their promise for enhanced PAH-targeted delivery,” the researchers wrote.
Form of Apelin helps reduce heart enlargement, scarring in rat models
In this rat model of PAH, CAR-Apelin extracellular vesicles significantly reduced heart enlargement and scarring compared with a control apelin peptide. They also helped clear blocked blood vessels in the lungs, reducing the amount of blockage to about two-thirds of what was observed without treatment.
CAR-Apelin extracellular vesicles improved blood flow through the lungs, as shown by heart ultrasound readings, and also reduced strain on the right side of the heart, while improving heart structure and function. These results outperformed what was seen in both untreated rats and those given the control apelin peptide.
Collectively, these results demonstrate that CAR-Apelin [extracellular vesicles] significantly improve both cardiac and pulmonary function across distinct PAH models, underscoring their broad therapeutic potential for PAH.
To confirm these benefits in another model of PAH, the researchers used mice with a more severe form of the disease. Unlike control extracellular vesicles, CAR-Apelin extracellular vesicles reduced blood pressure in the lungs to normal levels.
“Collectively, these results demonstrate that CAR-Apelin [extracellular vesicles] significantly improve both cardiac and pulmonary function across distinct PAH models, underscoring their broad therapeutic potential for PAH,” the researchers concluded.
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