Objective To study the presence of microflammation state in ESRD patients and the relationship between microinflammation state and atherosclerosis. Methods Inflammatory cytokines and carotid artery B ultrasound data of 246 ESRD patients and 43 cases with normal renal function as control were collected. The presence of microflammation state and its relationship to atherosclerosis were studied. Results The levels of inflammatory cytokines(CRP,IL 6,TNF ?)in ESRD patients were mostly in normal range, but still much higher than those in control.According to the level of CRP,the patients were divided into three groups.Significant differences of carotid artery B ultrasound and prevalence of cerebrocardiovasculer events were found between two groups with CRP levels less and higher than 4 mg/L. According to the history of atherosclerosis cerebrocardiovasculer disease,patients were divided into two groups. Levels of CRP, IL 6, TNF ?were higher in patients with cerebrocardiovasculer disease than those in patients without, but still in normal range. Conclusions There is a microinflammation status in ESRD patients. The microinflammation status may be a risk factor of high prevalence and mortality of atherosclerosis related cardiovascular events in ESRD patients.

OBJECTIVETo investigate the effects of angiotensin II (Ang II) antagonist telmisartan on retina vessel endothelial cell apoptosis and its impact on the ACE2-Ang-(1-7)-Mas axis in spontaneous hypertensive rats (SHR).

METHODSThirty-six SHR 16 week-old were randomly divided into 3 groups (n = 12 each): SHR, SHRT (telmisartan 10 mg · kg-1 · d-1 by gastric gavage) and SHRTA group (telmisartan 10 mg · kg-1 · d-1 by gastric gavage plus intravenous injection of A-779 0.5 mg · kg-1 · d-1), twelve WKY rats served as normotensive control group. Systolic blood pressure was measured at pre-treatment and 8 weeks later. After 8 weeks, rats were sacrificed, the expression of ACE2 and Mas in retina were analyzed by qRT-PCR, Western blot and Immunohistochemistry, the Ang-(1-7) concentration in serum was measured by ELISA. Specimens were obtained and stained by hematoxylin and eosin, and the morphology of retina vessel was observed. Apoptosis of vessel endothelial cells were determined by using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling method.

RESULTSThe systolic blood pressure of SHR, SHRT and SHRTA groups at baseline were significantly higher than age-matched WKY group (all P < 0.01). Eight weeks later, the systolic blood pressure group was significantly lower in SHRT group than in the SHR group (P < 0.01), this effect was partly reversed in SHRTA group. The retinal ACE2 mRNA and protein expression was significantly lower in SHR group than in WKY and SHRT groups (P < 0.01), which was similar between SHRT group and SHRTA group (P > 0.05). The retinal Mas mRNA and protein expression were significantly lower in SHR group compared to WKY and SHRT groups (all P < 0.01), which was significantly lower in SHRTA group than in the SHRT group (P < 0.05). ELISA results showed that serum Ang-(1-7) protein level was significantly lower in SHR group than in WKY group and SHRT group (both P < 0.05), which was lower in SHRTA group compared to SHRT group. Retinal vessel endothelial cell apoptosis was higher in SHR group than in WKY group, which could be reduced by cotreatment with telmisartan and this beneficial effect could be reversed by A-779.

CONCLUSIONTelmisartan can reduce retinal vessel endothelial cell apoptosis via upregulating the ACE2-Ang-(1-7)-Mas axis.

Angiotensin I ; metabolism ; Angiotensin II ; analogs & derivatives ; Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Apoptosis ; drug effects ; Benzimidazoles ; pharmacology ; Benzoates ; pharmacology ; Blood Pressure ; Endothelial Cells ; Peptide Fragments ; metabolism ; Peptidyl-Dipeptidase A ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Retina ; Systole ; Up-Regulation

Blood-brain barrier (BBB) damage after ischemia significantly influences stroke outcome. Compound LFHP-1c was previously discovered with neuroprotective role in stroke model, but its mechanism of action on protection of BBB disruption after stroke remains unknown. Here, we show that LFHP-1c, as a direct PGAM5 inhibitor, prevented BBB disruption after transient middle cerebral artery occlusion (tMCAO) in rats. Mechanistically, LFHP-1c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity, but also reduced the interaction of PGAM5 with NRF2, which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia. Furthermore, LFHP-1c administration by targeting PGAM5 shows a trend toward reduced infarct volume, brain edema and neurological deficits in nonhuman primate