Altogether, these results suggest that pericytes are implicated in the formation of JNJ-42041935 vascular calcification. Resident vascular pericytes may have a protective effect against the development of vascular calcification by regulating the balance of mineral formation together with other cells such as monocytes/macrophages. Exposure to inflammatory atherosclerotic stress induces pericytes to differentiate towards an osteoblastic lineage and secrete various mediators, including OPG, which trigger an imbalance between mineral formation and resorption in the plaque. As a result, intense calcification, and in some cases OM, develop within atherosclerotic lesions which ultimately may stabilize the plaque. SPATEs are secreted members of the autotransporter family, whose secretion involves the excision of the N-terminal region, known as the ����passenger domain����, from the C-terminal region or ����b-domain domain����, and subsequent release of the passenger domain into the cell surroundings. The SPATE family, which now includes more than 25 proteases, has been phylogenetically divided into class-1 and class-2 based on the amino acid sequence of the passenger domain. The bifurcation of SPATEs into two classes is consistent with structural differences and biological effects. Class-1 SPATEs such as Pet, SigA, Sat, and EspC for example, display similar substrate specificity, consistent cytotoxic effects on cultured cells, and enterotoxin activity on intestinal tissues. On the other hand, most knowledge on class 2 SPATEs comes from two members of this family: Tsh/Hbp and the Pic protease. Tsh, the first class-2 SPATE isolated from a septicemic pathogen in poultry, was found to confer hemagglutination and binding to extracellular matrix proteins, such as BIX-01294 fibronectin and collagen IV. Subsequently, Hbp identified in the E. coli strain, isolated from a human wound infection, was shown to differ from Tsh in only two residues. Hbp was able to interact with hemoglobin, to degrade it, and subsequently to bind the released heme suggesting a role for Hbp in heme acquisition.