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. Author manuscript; available in PMC: 2023 Dec 6.
Published in final edited form as: Sci Signal. 2022 Dec 6;15(763):eabn2743. doi: 10.1126/scisignal.abn2743

Figure 8. Schematic representation of the mechanism by which decreased TSC2 abundance in PAVSMCs promotes pulmonary vascular remodeling and PH.

Figure 8.

Decreased TSC2 abundance in PAH PAVSMCs, caused predominantly by the ECM stiffening, results in excessive production of fibronectin, ECM remodeling, over-accumulation of YAP/TAZ, and activation of mTOR, leading to increased proliferation of PAVSMCs and PAAFs, reduced apoptosis of PAVSMCs, pulmonary vascular remodeling, and pulmonary hypertension. The SIRT1 activator SRT2104 restores functional TSC2, resolves the molecular and cellular abnormalities caused by decreased TSC2 protein content, and attenuates pulmonary vascular remodeling and pulmonary hypertension.