Multiple 3 m sections were cut from the TMA blocks and transferred to ultrafrost slides

lthough the underlying causes of ethnic differences in vascular calcification are not well established. Reinforcing these ethnic differences, AAs are at lower risk for myocardial infarction based on less order SB-366791 coronary artery calcification, and they have significantly lower rates of myocardial infarction than EAs, provided equal access to healthcare. It has been suggested that AAs may be less susceptible than whites to hyperglycaemiainduced macrovascular disease. Thus, these findings may explain the differences observed in the relationship between vascular disease and DKK1 between our study and the data from Register and colleagues. Recent data suggest that the association between vascular calcification and osteoporosis is not simply a consequence of age, stressing that the co-incidence of vascular calcification with low bone activity and osteoporosis could be biologically linked. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19691102/ During the development of vascular calcification, there is a transition of vascular SMCs towards an osteoblast- like phenotype, which promotes the mineralization within these structures. In this process there are several players, including those related to mineral metabolism, like phosphorus, calcium or parathyroid hormone, which influences the expression of osteogenic factors. There is emerging evidence suggesting that some inhibitors of the Wnt pathway, such as secreted frizzled Proteins 2 and 4 and DKK-1, may play a role linking vascular calcification and bone loss. AAs manifest a skeletal resistance to the effects of parathyroid hormone and exhibit opposite relationships between arterial calcification and serum vitamin D concentrations compared with Europeans. In our opinion, these ethnic differences in the effects of calciotropic hormones on bone and vessels may indicate that differences in other pathways, as Wnt pathway, may be expected according to race. However, this hypothesis must be confirmed. There are other differences between the study from Register and colleagues and ours, which may explain the discrepancy of results. First, the prevalence of cardiovascular disease is lower, 27%, compared to our study where a 58% of patients had previous cardiovascular disease. Second, in the study from Register and colleagues 28,3% of subjects were taking hormonal therapy while no women were on hormonal therapy in our study. Estradiol and progesterone has shown to regulate Wnt pathways in endometrial tissue and brain, so an influence of hormonal therapy in DKK1 concentrations can not be excluded. Finally, despite the low expected incidence of arterial calcification in AAs, in the study from Register and colleagues there is a high prevalence of aortic calcification. Thus, differences between study populations apart from the ethnicity may influence the discrepancy of results. There are no previous studies evaluating differences in serum DKK1 concentrations according to the presence of diabetes. We did not find differences in DKK1 between T2DM patients and subjects without diabetes. These results contrast with our previous data showing higher sclerostin concentrations in the same group of type 2 diabetes patients. However, serum DKK1 and sclerostin have shown to be barely correlated, as we found in our sample. In addition, the effects of DKK1 and sclerostin PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19690573 may differ due to differences in Kremen binding. While DKK1 is always an inhibitor of Wnt signaling, the effect of sclerostin is variable depending on context. Unlike our previous results about sclerostin, women had