Research ArticlePulmonary Hypertension

Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension

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Science Translational Medicine  07 Oct 2015:
Vol. 7, Issue 308, pp. 308ra159
DOI: 10.1126/scitranslmed.aaa9712

A smooth transition in pulmonary hypertension

Recently, researchers sought to explain the incredible growth rate of the superheroes the Incredible Hulk and Captain America. Although no “super-soldier serum” exists, they decided it might be possible to recreate such a rapid increase in muscle mass through gene editing, but ultimately, the transformation could be “traumatic.” In a real-life situation, Sheikh and colleagues similarly investigated how the overgrowth of smooth muscle in the vasculature happens in pulmonary hypertension, with the hopes of targeting this process and preventing the onset of PH—a disease with few therapeutic options. In PH, normally unmuscularized tissue becomes muscularized, likely due to low oxygen (hypoxia). The authors used a series of genetic mouse models to characterize a unique cell type that expressed a smooth muscle cell (SMC) marker and platelet-derived growth factor receptor-β (PDGFR-β), and reside at the border zone of muscle and nonmuscle in the pulmonary arterioles. Knowing that these precursor cells are “primed” to become arteriole SMCs, Sheikh et al. tracked the cells over time, in living mice, during hypoxia-induced PH and discovered that the SMCs expanded clonally (from a single, specialized cell). Human pulmonary artery SMCs expressed high levels of a factor known as KLF4, which is downstream in PDGF signaling. Back in the mice, the authors found that KLF4 was required by the SMCs to migrate distally and “muscularize.” This novel SMC precursor therefore plays a major role in PH, and—perhaps much to the benefit of our favorite superheroes’ enemies—targeting the now-clear mechanisms of SMC migration and proliferation could prevent the characteristic muscular transition in disease.

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