Dr. Edward Dempsey and colleagues of the University of Colorado observed that neprilysin protects against PHTN.
Patients with pulmonary hypertension, an increase in pressure in blood vessels in the lung, may exhibit shortness of breath, dizziness, or fainting, especially while exercising. Hypoxic pulmonary hypertension is caused by lack of oxygen, often due to other lung or heart disorders. One complicating factor in PHTN is vascular remodeling, where the blood vessels of the lung and the muscles surrounding them are permanently altered by the hypertension.
Neprilysin is a protein that is expressed within the blood vessels of the lung. Neprilysin breaks down neural signaling molecules that regulate both growth and contraction of the muscle cells around the blood vessels. To determine if depletion of neprilysin increased susceptibility to PHTN in response to chronic hypoxia, Dempsey et al generated a mouse model deficient in neprilysin. Although neprilysin deficiency had minimal effects on baseline cardiac and pulmonary function, upon hypoxic exposure, neprilysin-deficient mice had an augmented pulmonary hypertensive response. In addition, Dempsey et al observed increased proliferation of pulmonary smooth muscle cells in these mice, which was reduced upon reintroduction of neprilysin. Thus, introduction of neprilysin into the lungs of PHTN patients may provide a novel treatment for PHTN.
The neprilysin deficient mouse model of PHTN created by Dempsey et al demonstrates "changes in the pulmonary vasculature … , which are similar to those found in large animal models of hypoxic PHTN that closely parallel human disease and are usually not associated with mouse models of chronic hypoxic PHTN. [Demsey et al] believe that further work with the [neprilysin deficient] mouse model of chronic hypoxic PHTN may lead to the identification of new therapeutic strategies or targets to limit or reverse this important clinical problem."
- Dempsey et al. Neprilysin Null Mice Develop Exaggerated Pulmonary Vascular Remodeling in Response to Chronic Hypoxia. American Journal Of Pathology, 2009; 174 (3): 782 DOI: 10.2353/ajpath.2009.080345
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