In particular, in patients with sPAP measurements lower than 40 mmHg, TIMP-4 levels were comparable to those of controls, while individual sPAP measurements suggestive of PAH were found to be associated with increased TIMP-4 levels, indicating a cardiopulmonary vasculature-specific role of TIMP-4 activation in SSc [114]. This evidence concerns the gene PDZK1IP1 and pulmonary arterial hypertension.