This schema incorporates the findings described in our article and the literature to date as discussed. (A) BMP-2 inhibits SMC proliferation via PPARγ and apoE. apoE impairs PDGF-BB/MAPK signaling by binding to LDL receptor–related protein (LRP), thereby initiating endocytosis and degradation of the LRP/PDGFR-β/PDGF-B complex. PPARγ induces LRP and other growth-inhibitory/proapoptotic genes in SMCs and inhibits cell-cycle and other growth-promoting genes such as telomerase, cyclin D1, and retinoblastoma protein. Moreover, PPARγ induces phosphatases that can directly inactivate phospho-ERK. (B) BMP-RII dysfunction promotes SMC proliferation and survival in PAH. Heightened PDGF-BB signaling leading to SMC proliferation is a key clinical feature of PAH. Deficiency of both apoE and LRP enhances mitogenic PDGF-BB/MAPK signaling. Loss-of-function mutations in the BMP-RII gene will decrease endogenous PPARγ activity, leading to unopposed MAPK signaling, SMC proliferation and survival, and ultimately development of PAH.TF, transcription factor. (C) PPARγ agonists can rescue BMP-RII dysfunction and reverse PAH. PPARγ agonists such as rosiglitazone or pioglitazone might reverse SMC proliferation and vascular remodeling in PAH patients with or without BMP-RII dysfunction via induction of apoE and other growth-inhibitory/proapoptotic genes (as indicated) and through repression of growth-promoting genes (not shown).