Pulmonary arterial hypertension (PAH) – high blood pressure in the lungs – has been linked to both heritable and idiopathic (spontaneous) causes. The underlying vascular changes that cause PAH are unclear and previous attempts to study changes in patient tissues have been limited by end-stage disease effects.
Now, Susan Majka, Ph.D., associate professor of Medicine at Vanderbilt University, and colleagues have brought a new approach to the study of PAH pathogenesis.
The researchers used skin cells from PAH patients to derive induced pluripotent stem (iPS) cells – cells that can grow in culture and “mature” into vascular cell types. They examined patterns of gene expression in vascular mesenchymal cells and endothelial cells derived from the PAH patient-specific iPS cells, and they identified alterations in the Wnt signaling pathway. The researchers validated these findings in primary patient vascular cells and found similar altered patterns of gene expression in skin cells from patients with heritable and idiopathic PAH.
Their report in the Sept. 1 American Journal of Physiology – Cell Physiology suggests that the molecular lesions that cause PAH are present in all cell types evaluated and that stimulation of the Wnt signaling pathway is a common molecular defect in both heritable and idiopathic PAH.
The study offers a unique resource – patient-derived iPS cells – to the global pulmonary hypertension research community. These cells will enable further studies of the molecular defects that lead to PAH and will provide useful models for testing potential therapies.
The research was supported by grants from the American Heart Association and the National Institutes of Health (HL091105, HL116597, DK094132).
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