In a recent study from the University of California San Diego, researchers found how to reverse high blood pressure in the lungs.
Pulmonary arterial hypertension (PAH) is a type of high blood pressure in the lungs, in which blood vessels are narrowed, blocked, or destroyed, causing the heart to work harder and, in time, result in cardiac weakness and failure.
The disease is relatively rare, but affects an estimated 100,000 persons in the United States, and results in 20,000 deaths annually. There is no cure.
In the study, researchers found the underlying signaling pathway that causes PAH—and a novel antibody therapy that blocks the abnormal blood vessel formation in the disease.
At the cellular level, PAH progresses with the proliferation of vascular smooth muscle cells (vSMC) that cause small arteries in the lungs to become narrowed, leading to progressively less oxygen in the blood.
The team focused on overexpression of the NOTCH ligand JAGGED-1, a binding protein involved in cell signaling, and, in this case, the development of small pulmonary vSMCs.
They found that overexpression of the NOTCH3 ligand, JAGGED-1, spurs vSMC proliferation, but the NOTCH3 ligand DELTA-LIKE 4 inhibits it.
The researchers then developed an antibody therapy that selectively blocks JAGGED-1-induced NOTCH3 signaling.
This effectively reversed pulmonary hypertension in two rodent models of the disease, with no toxic side effects.
The team says these findings show two opposing roles of NOTCH ligands.
Importantly, it opens the door to a potentially new, safe treatment for PAH, using a monoclonal antibody that selectively inhibits NOTCH3 activation in the lungs.
If you care about lung health, please read studies about how COVID-19 damages lungs, and how to take care of your lungs during COVID and beyond.
For more information about lung health, please see recent studies about vaping marijuana linked to more lung damage, and results showing this newly approved drug can effectively fight lung cancer.
The research is published in Science Translational Medicine and was conducted by Patricia A. Thistlethwaite et al.
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