Science & Technology

Prevention of Pulmonary Arterial Hypertension-Incurable Disease

Researchers at the University of California, San Diego explain the opposite cellular signal imbalance that causes fatal disease and how new monoclonal antibody therapies treat or prevent it.

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.

Researchers at the University of California, San Diego (UCSD) School of Medicine, in a study published May 4, 2022, found a new monoclonal antibody therapy that blocks the underlying signaling pathways that lead to PAH (and the abnormal angiogenesis of the disease). ) Is explained.journal Scientific translation medicine..

Thickening of pulmonary hypertension of the arterial wall

Evidence of pulmonary hypertension is evident in the thickening of the arterial wall.Credit: Wikimedia Commons

PAH progresses at the cellular level by the growth of vascular smooth muscle cells (vSMC). This causes the arterioles in the lungs to contract, resulting in less and less oxygen in the circulation. Overexpression of the NOTCH ligand JAGGED-1, a binding protein involved in cell signaling, in this case the development of a small lung vSMC, was the focus of a research team led by senior authors Patricia A. Thistlethwaite, MD, Ph.D. .. .. , Professor of Surgeons, UC San Diego Medical Center and Cardiothoracic Surgeon, UC San Diego Health.

They found that overexpression of the NOTCH3 ligand JAGGED-1 promoted vSMC proliferation and that DELTA-LIKE4 inhibited it. The researchers then selectively blocked JAGGED-1 -induced NOTCH3 signaling and effectively treated pulmonary hypertension in two rodent models of the disease without causing adverse side effects. I have created a therapeutic monoclonal antibody to be used.

“These findings reveal two conflicting roles for NOTCH ligands,” said Thistlethwaite. “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.”

Reference: “JAGGED-NOTCH3 Signal Transduction in Vascular Remodeling of Pulmonary Arterial Hypertension” Yu Zhang, Moises Hernandez, Jonathan Gower, Nolan Winicki, Xena Morataya, Sebastian Alvarez, Jason X.-J. A. Sisleswaite, May 4, 2022, Scientific translation medicine.
DOI: 10.1126 /scitranslmed.abl5471

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.

Funding for this study was in part from the National Institutes of Health (Grants R01HL119543 and R01HL132225).



Prevention of Pulmonary Arterial Hypertension-Incurable Disease

https://scitechdaily.com/preventing-pulmonary-arterial-hypertension-an-incurable-disease/ Prevention of Pulmonary Arterial Hypertension-Incurable Disease

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