Consistent with recent studies highlighting on the novel roles of TLR2/4 signaling in cardiovascular diseases such as atherosclerosis and hypertension via endogenous signals from damaged or stressed cells [16], [27]–[30], known as DAMPs, the present study is the first to show that TLR2 was highly upregulated in the small PA endothelium of both calf and human subjects with pulmonary hypertension and stiffened proximal PAs. Here, TLR2 is linked to pulmonary hypertension.