Adipose tissue releases several of these inflammatory factors in obese subjects, which may contribute to elevated blood levels and diseases pathogenesis. Thus, it is 1062368-24-4 possible that the inflammatory Proteasome inhibitor changes we have observed in adipose tissue of PHPT patients may result in increased circulating levels of pro-inflammatory factors, thereby increasing the risk of CVD. S100A8 and S100A9 were the most up-regulated genes in the adipose tissue of PHPT patients compared to controls. These genes belong to a subgroup of the S100 family termed calgranulins, which are highly expressed in monocytes. Calgranulins mediate the induction of neutrophil chemotaxis and adhesion and have an important role in tissue inflammation . Elevated levels of calgranulin are found in a wide range of acute and chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowl disease and asthma as well as in cancer . It has been shown that calcium-mediated signalling is necessary for the release of S100A8/A9 , suggesting that their expression and possible release from adipose tissue may be increased due to elevated calcium levels in PHPT patients. Several genes encoding the complement cascade were upregulated in PHPT patients, including complement component 1 and the s-, q- and r- subcomponents of C1. The complement cascade comprises more than 30 proteins produced by various cell types, mainly hepatocytes but also monocytes and macrophages in various tissues. Activation of the complement cascade is often antibody-mediated, although antibody-independent mechanisms can act as initiators. Cleavage of C1 into C1Q, C1R and C1S further activates the cascade. This complement activation leads to production of biologically active molecules contributing to inflammation . In our study MMP9 was one of the most up-regulated genes in adipose tissue in PHPT patients compared to controls. Matrix metallopeptidases are a family of zinc-dependent endopeptidases involved in the degradation and reorganisation of extracellular matrix . Elevated circulating levels of MMP-9 may play a role in the development of hypertension and increased risk of death by CVD . Moreover, MMP-9 has been implicated in atherosclerosis and atherosclerotic plaque stains positive for MMP-9 by immunhistochemistry . In one study of 473 subjects, blood levels of MMP-9 were associated with grade of atherosclerosis in the femoral artery .