Targeting Molecular Pathways That Cause Pulmonary Arterial Hypertension-ScienceDaily

Pulmonary arterial hypertension (PAH) is a type of pulmonary hypertension in which blood vessels become narrowed, clogged, or destroyed, causing the heart to work harder and eventually cause heart weakness and dysfunction. ..

Although the disease is relatively rare, it affects an estimated 100,000 people in the United States and kills 20,000 people annually. There is no cure.

In a study published on May 4, 2022 Scientific translation medicineResearchers at the University of California, San Diego Medical School, describe the underlying signaling pathways that lead to PAH and new monoclonal antibody therapies that block the abnormal angiogenesis that is characteristic of the disease.

At the cellular level, PAH progresses with the proliferation of vascular smooth muscle cells (vSMCs), narrowing the arterioles of the lungs and gradually reducing oxygen in the blood. The research team, led by senior author Patricia A. Sislswaite School of Medicine, is a professor of surgery at the University of California, San Diego School of Medicine, a cardiothoracic surgeon at the University of California, San Diego Health, and focuses on overexpression of the NOTCH ligand JAGGED-1. I’m guessing. Cellular signaling, in this case a binding protein involved in the development of small lung vSMCs.

They found that overexpression of the NOTCH3 ligand JAGGED-1 promoted vSMC proliferation, but the NOTCH3 ligand DELTA-LIKE4 inhibited it. The researchers then selectively blocked JAGGED-1 -induced NOTCH3 signaling and effectively reversed pulmonary hypertension in two rodent models of the disease without toxic side effects. Developed a monoclonal antibody for.

“These findings reveal two conflicting roles for NOTCH ligands,” said Sisleswaite. “Importantly, using monoclonal antibodies that selectively inhibit NOTCH3 activation of the pulmonary vascular system opens the door to potentially new and safe treatments for PAH.”

Co-authors include Yu Zhang, Moises Hernandez, Jonathan Gower, Nolan Winicki, Xena Morataya, Sebastian Alvarez, Jason X.-J. Former and John Sea, all at the University of California, San Diego.

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material Provided by University of California, San Diego.. Original written by Scott Rafe. Note: Content can be edited in style and length.

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