SMAD3 and pulmonary arterial hypertension: We show that TLR4 is required for expression of IL-6 and SNAIL and that MCAM is required for VCAM1, and that while both receptors activate p-p38 and NF-κB, different signaling molecules are required to induce coactivating transcription factors, i.e., p-STAT1 for IL-6, p-JNK–mediated p-SMAD3 for SNAIL, and p-ERK–mediated ATF2 for VCAM1. The studies do reinforce the need for novel therapies in PAH such as the use of TLR4 inhibitors currently in clinical trial for autoimmune disease (46).