Elevated expression of periostin in diabetic cardiomyopathy and the effect of valsartan.

BACKGROUND: Periostin, an extracellular matrix protein, plays a significant role in adverse cardiac remodeling. However, no report has documented the function of periostin in left ventricular remodeling of streptozototin (STZ)-induced diabetic rats. The aim of the present study was to observe the expression of periostin in Wistar rat's myocardium of diabetic cardiomyopathy (DCM) and the effect of valsartan on it. METHODS: Immunohistochemistry, real-time polymerase chain reaction, and Western blot analysis were used to determine the degree of expression and location of periostin, transforming growth factor (TGF)-ß1, TGF-ß1 type II receptor (TGF-ß1 R II), and Type I and III collagens in the myocardium of STZ-induced diabetic rats. RESULTS: Periostin, TGF-ß1, TGF-ß1 R II, and Type I and III collagens were significantly increased in the myocardium of diabetic rats compared with control group on both messenger ribonucleic acid and protein levels. In addition, diabetic rats treated with valsartan could have reduced expression of periostin and improved cardiac remodeling of DCM. CONCLUSIONS: Periostin may play a crucial role in cardiac remodeling and myocardial interstitial fibrosis process of DCM and it could be one of the important mechanisms for valsartan to improve the ventricular remodeling of DCM.

[Implication of elevated expression of receptor for activated C kinase 1 in mononuclear cells and coronary atherosclerotic plaques from patients with coronary artery disease].

OBJECTIVE: To observe the expression and clinical implication of receptor for activated C kinase 1 (RACK1) in mononuclear cells and coronary atherosclerotic plaques from patients with coronary artery disease. METHODS: mRNA and protein expressions of RACK1 were detected in mononuclear cells from 29 patients with stable angina pectoris (SAP), 41 patients with acute coronary syndrome (ACS) and 30 healthy volunteers. RACK1 protein expression was also detected by immunohistochemistry in 17 coronary atherosclerotic plaques and 6 normal autopsy coronary samples. RESULTS: (1) mRNA expression of RACK1 was significantly upregulated in mononuclear cells from patients with ACS compared with those from patients with SAP (18.71 ± 5.45 vs. 12.18 ± 4.14, P < 0.05), and the latter was also significantly higher than in healthy controls (12.18 ± 4.14 vs. 3.65 ± 1.57, P < 0.05). (2) Similar changes were observed for protein expression of RACK1 for the three groups. (3) Increased expression of RACK1 was found in atherosclerotic plaques, especially in unstable plaques, positive RACK1 stain was evidenced in foam cells, inflammatory cells, smooth muscle cells and endothelial cells. CONCLUSIONS: The expression of RACK1 is significantly upregulated in mononuclear cells from patients with coronary artery disease, especially in patients with ACS, and in coronary atherosclerotic plaques, especially in unstable plaques. Our results thus suggest that RACK1 might play an important role in the development and progression of coronary artery disease.

SagE induces highly effective protective immunity against Streptococcus iniae mainly through an immunogenic domain in the extracellular region.

BACKGROUND: Streptococcus iniae is a Gram-positive bacterium and a severe pathogen of a wide range of farmed fish. S. iniae possesses a virulence-associated streptolysin S cluster composed of several components, one of which is SagE. SagE a transmembrane protein with one major extracellular region named ECR. This study aimed to develop a SagE-based DNA candidate vaccine against streptococcosis and examine the immunoprotective mechanism of the vaccine. RESULTS: We constructed a DNA vaccine, pSagE, based on the sagE gene and examined its immunological property in a Japanese flounder (Paralichthys olivaceus) model. The results showed that at 7 days post-vaccination, expression of SagE at transcription and translation levels was detected in the tissues of the vaccinated fish. After challenge with S. iniae at one and two months post-vaccination, pSagE-vaccinated fish exhibited relative percent survival (RPS) of 95% and 88% respectively. Immunological analysis showed that (i) pSagE significantly upregulated the expression of a wide range of immune genes, (ii) pSagE induced the production of specific serum antibodies that bound whole-cell S. iniae, and (iii) treatment of S. iniae with pSagE-induced antibodies blocked bacterial invasion of host cells. To localize the immunoprotective domain of SagE, the ECR-expressing DNA vaccine pSagEECR was constructed. Immunization analysis showed that flounder vaccinated with pSagEECR exhibited a RPS of 68%, and that pSagEECR induced serum antibody production and immune gene expression in a manner similar to, though to lower magnitudes than, those induced by pSagE. CONCLUSIONS: We in this study developed a DNA vaccine, pSagE, which induces highly protective immunity against S. iniae. The protective effect of pSagE is probably due to its ability to elicit systemic immune response, in particular that of the humoral branch, which leads to production of specific serum antibodies that impair bacterial infection. These results add insights to the immunoprotective mechanism of fish DNA vaccine.