Scientists from the University of California San Diego found how to treat high blood pressure in the lungs.
The research is published in Science Translational Medicine and was conducted by Patricia A. Thistlethwaite et al.
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, the team 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 high blood pressure, please read studies about stuff that could cause nighttime high blood pressure, and this diet could help reduce high blood pressure, diabetes.
For more information about lung health, please see recent studies about drug that could help treat COVID-19 lung inflammation, and results showing the cause of lung cancer in never smokers.
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