High-dose atorvastatin improves vascular endothelial function in patients with leukoaraiosis.

OBJECTIVE: Leukoaraiosis (LA), as an age-related white matter degeneration, is mainly caused by chronic ischemia. Our study aims to explore the efficacy of different doses of atorvastatin (ATV) in the vascular endothelial function in patients with LA. METHODS: Our study enrolled 402 LA patients who were then randomly included as control or treated with ATV (10 mg), ATV (20 mg), or ATV (30 mg). The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected by enzyme colorimetric assay. The high-sensitivity C-reactive protein (hs-CRP) level, reactive hyperemia index (RHI), endothelin-1 (ET-1) content, and nitric oxide (NO) level were tested by latex agglutination test, peripheral arterial tonometry technology, radioimmunoassay, and nitrate reductase assay, respectively. RESULTS: After 8 weeks of ATV treatment, the levels of TC, LDL-C, and HS-CRP decreased significantly, and the trends were demonstrated in a more significant way with the increases of dose of ATV. The treatment with ATV at different doses elevated NO level and RHI and declined ET-1 content. Gastrointestinal reaction, muscular pain, and increased aminopherase were observed after treatment with the ATV at different doses with more obvious symptoms detected accompanied by the increase of the dose. The RHI was in negative correlation with the ET-1 and HS-CRP while in positive correlation with NO. CONCLUSION: Our study demonstrates that ATV can significantly improve the vascular endothelial function in LA patients with a dose-dependent effect.

Protective effects of tanshinone IIA on myocardial ischemia reperfusion injury by reducing oxidative stress, HMGB1 expression, and inflammatory reaction.

CONTEXT: Although there were reports on the protective functions of tanshinone IIA (TSA) on rat myocardial ischemia, the exerting mechanism has not been completely clarified. OBJECTIVE: An attempt was made to further verify the protective effect of TSA on myocardial ischemia reperfusion injury and elucidate its underlying mechanism. MATERIALS AND METHODS: The rats were given TSA (10, 20, and 40 mg/kg bw per day) in intraperitoneal injection for 15 d. Rami anterior descending branch of coronary artery was ligated for 30 min and then re-perfused for 120 min to establish a reperfusion model. Effects of TSA on the infarct area, creatine kinase (CK), aspartate aminotransferase (AST), high mobility group box B1 protein (HMGB1), and inflammation and oxidation were investigated. RESULTS: Compared with those in the IR group, infarct size percentages of rats' myocardium in L-TSA, M-TSA, and H-TSA groups were reduced by 1.21, 4.26, and 12.50%, respectively, CK activities by 7.4, 11.2, and 12.5%, respectively, and AST activities also declined (p < 0.05). Furthermore, compared with those in the IR group, SOD and GSH-Px activities increased, and MDA, TNF-α, IL-6, and iNOS levels decreased in L-TSA, M-TSA, and H-TSA groups (p < 0.05). Meanwhile, compared with those in the IR group, HMGB1 expressions in L-TSA, M-TSA, and H-TSA groups were lowered by 21.9, 32.4, and 35.6%, respectively. DISCUSSION AND CONCLUSION: The protective function of TSA on myocardial ischemia reperfusion injury may be possibly exerted by inhibiting the increase of ROS caused by the reperfusion to attenuate the expression of HMGB1 and inhibit inflammation.

Trimethylamine-N-oxide: a potential biomarker and therapeutic target in ischemic stroke.

Ischemic stroke is by far the most common cerebrovascular disease and a major burden to the global economy and public health. Trimethylamine-N-oxide (TMAO), a small molecule compound produced by the metabolism of intestinal microorganisms, is reportedly associated with the risk of stroke, as well as the severity and prognosis of stroke; however, this conclusion remains contentious. This article reviews the production of TMAO, TMAO's relationship with different etiological types of ischemic stroke, and the possibility of reducing TMAO levels to improve the prognosis of ischemic stroke.

Downregulation of ICCs and PDGFRα+ cells on colonic dysmotility in hirschsprung disease.

Background: To investigate the effect of the distribution and expression of interstitial cells of Cajal (ICCs) and platelet-derived growth factor receptor-α positive (PDGFRα+) cells in different colon segments on colonic motility in children with Hirschsprung disease (HSCR). Methods: Smooth muscles of the narrow and dilated segments of the colon were obtained from 16 pediatric patients with HSCR. The proximal margin was set as the control section. The mRNA and protein expressions of c-Kit, PDGFRα, ANO1, and SK3 channels were examined. Circular smooth muscle strips of the colon were prepared for performing electrophysiology experiments using electric field stimulation (EFS) and intervention from different drugs (TTX, NPPB, Apamin, L-NAME, and CyPPA). Results: The mRNA and protein expressions of c-Kit, ANO1, PDGFRα, and SK3 were much lower in the narrow segment than those in the dilated and proximal segments of the colon. The narrow segment showed a considerably spontaneous contraction of the muscle strip. After the EFS, the relaxation response decreased from the proximal to the narrow segment, whereas the contraction response increased. TTX blocking did not cause any significant changes in the narrow segment. In contrast, when NPPB, Apamin, L-NAME, and CyPPA were used to intervene in the muscle strips, the proximal segment showed a more sensitive inhibitory or excitatory response than the narrow segment. Conclusions: Downregulation of the ICCs and PDGFRα+ cells from the proximal to narrow segment may be responsible for the dysmotility of the colon in pediatric HSCR.

Polymorphism of klotho G-395A and susceptibility of coronary artery disease in East-Asia population: a meta-analysis.

OBJECTIVE: To investigate the association between polymorphism of Klotho G-395A and susceptibility of coronary artery disease (CAD) in East-Asia population. METHODS: A total of 6 case-control studies involving 1560 patients and 1459 controls were analyzed in the study. PubMed, Embase, CBM disc, Wanfang database were searched for published case-control studies investigating the association between Klotho G-395A and CAD that were available before Dec. 2013. Fixed or random effect models were selected for odds ratio (OR) calculation. A Meta-analysis was performed to estimate heterogeneity and the pooled odds ratio (OR) to evaluate the relationship between Klotho G-395A polymorphism and CAD. The sensitivity analysis was also assessed. RESULTS: There was no significant heterogeneity found (dominant genetic model: P = 0.2, I(2) = 30.8%). The pooled OR (95% CI) value of the frequencies of the Klotho G-395A genotype (GA + AA)/GG calculated by fixed effects mode was 1.24 (95% CI:1.06-1.45), P = 0.009. There was no significant heterogeneity among the remaining articles after using random effect model or excluding the article with the largest weight or the article with larger frequencies of the allele A, respectively. And the pooled OR (95% CI) value of the frequencies of the genotype (GA + AA)/GG were similar. Publication bias was not found by Begg's test. CONCLUSION: Klotho G-395A polymorphism may be a susceptible factor of CAD in East-Asia population.