Renal Angiotensin receptor type 1 and 2 upregulation in intrauterine growth restriction of newborn piglets.

Epidemiological and experimental studies suggest that intrauterine growth restriction (IUGR) is associated with abnormalities in kidney development which is thought to be linked with alterations causing adult cardiovascular diseases. The renin-angiotensin system (RAS) plays an important role in the development of renal vascular and tubular structures, and is known to be altered by experimentally induced IUGR. These experimental models of IGUR have been criticized because they may have a more severe impact on intrauterine development than that which is normally encountered in humans. Therefore, we asked whether naturally occurring small-for-gestational-age newborn piglets exhibit features of altered RAS activity. We investigated the regional renal expression of angiotensin II type 1 (AT1) and AT2 receptors in normal-weight and IUGR piglets. The AT1 receptor mRNA expression was markedly enhanced in IUGR piglets, in the renal cortex by 64% and in the renal medulla by 52% (p < 0.05, compared with normal littermates). In contrast, mRNA expression for the AT2 receptor was similar in both the normal-weight and IUGR piglets. A significantly higher AT1 receptor protein expression was found in the IUGR piglets (p < 0.05) in the glomeruli, in the proximal and distal tubules, as well as in the collecting ducts by immunohistochemistry. Furthermore, AT2 receptor protein expression was significantly higher in the IUGR piglets (p < 0.05) in the subcapsular nephrogenic zone and in the distal tubules and collecting ducts. Thus, IUGR is accompanied by an upregulation of angiotensin II receptor expression in the kidneys of newborn piglets. This may indicate an alteration of the RAS in newborns suffering from naturally occurring IUGR.

Identification of the receptor for advanced glycation end products in synovial tissue of patients with rheumatoid arthritis.

OBJECTIVES: Generation of advanced glycation end products (AGE) is an inevitable process in vivo and can be accelerated under pathologic conditions such as oxidative stress, e.g. in rheumatoid arthritis (RA). This process is mediated by the AGE-specific receptor (RAGE). In this study we analysed the presence of RAGE in RA and osteoarthritic (OA) synovial tissue using immunohistology. METHODS: Frozen synovial tissue samples from 11 RA patients and 12 OA patients were treated with goat anti-RAGE immunoglobulin G (IgG) and rabbit antigoat IgG. Immunostaining was visualised with streptavidin horse radish peroxidase (chromogen amino-ethyl-carbazole). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20. RESULTS: In 9/11 RA and 8/12 OA synovial specimens, RAGE was detected in synovial lining, sublining, and stroma. In RA, many T cells (CD45RO(+)) and some macrophages (CD68(+)) showed positive immunostaining for RAGE, whereas B cells were mostly negative. We found no difference in staining patterns between the RA and OA samples. CONCLUSIONS: We detected RAGE in RA and OA synovial tissue. The presence of RAGE on macrophages, T cells, and some B cells suggests its role in the pathogenesis of inflammatory joint disease.