In addition to suppressing tumors, the protein tuberous sclerosis complex 2 (TSC2) may play a role in preventing or treating pulmonary arterial hypertension (PAH), according to research at ATS 2019.
Researchers found that a deficiency of this protein produced dysfunctional molecules unable to support cell structure and function, resulted in thickening of pulmonary blood vessels and led to PAH.
Analysis of various pro-PH factors (substrate stiffness, extracellular matrix proteins, growth factors, pro-inflammatory mediators) revealed that only culturing on stiff substrates dramatically reduced TSC2 protein levels in non-diseased human PAVSMC. This was associated with increased cell growth, which was prevented by TSC2 re-expression.
“TSC2 acts as a mechanosensor and mechanotransducer, and its deficiency in PAH PAVSMC promotes activation of Yap/mTOR axis, excessive production of ‘diseased’ extracellular matrix, VSMC remodeling and PH,” the researchers wrote. “The restoration of TSC2 may be considered as a new potentially attractive therapeutic strategy to reverse pulmonary vascular remodeling and overall PH.”