Background. Hypercholesterolemia and disruptions of the blood brain barrier (BBB) have been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease (AD). Simvastatin therapy may be of benefit in treating AD; however, its mechanism has not been yet fully understood. Objective. To explore whether simvastatin could block disruption of BBB induced by cholesterol both in vivo and in vitro. Methods. New Zealand rabbits were fed cholesterol-enriched diet with or without simvastatin. Total cholesterol of serum and brain was measured. BBB dysfunction was evaluated. To further test the results in vivo, rat brain microvascular endothelial cells (RBMECs) were stimulated with cholesterol in the presence/absence of simvastatin in vitro. BBB disruption was evaluated. Results. Simvastatin blocked cholesterol-rich diet induced leakage of Evan's blue dye. Cholesterol content in the serum was affected by simvastatin, but not brain cholesterol. Simvastatin blocked high-cholesterol medium-induced decrease in TEER and increase in transendothelial FITC-labeled BSA Passage in RBMECs. Conclusions. The present study firstly shows that simvastatin improves disturbed BBB function both in vivo and in vitro. Our data provide that simvastatin may be useful for attenuating disturbed BBB mediated by hypercholesterolemia.

Nuclear factor-κB interacting long non-coding RNA (LncRNA NKILA) is a well-studied tumor suppressor lncRNA in several types of malignancies. The present study reports the involvement of this lncRNA in diabetic cardiomyopathy (DC). A 8-year-follow-up study on 312 diabetic patients without exhibiting obvious complications demonstrated that plasma lncRNA NKILA levels were upregulated specifically in diabetic patients who developed DC but not in patients with other complications. Plasma levels of lncRNA NKILA at 6 months prior to diagnosis is sufficient to distinguish patients with DC from other diabetic patients without significant complications. Although in vitro experiments demonstrated that lncRNA NKILA expression in cardiomyocyte cells was not affected by high-glucose treatment, ectopic lncRNA NKILA expression and lncRNA NKILA knockdown potentiated, and inhibited cardiomyocyte apoptosis, respectively. Therefore, the data from the present study suggests that overexpression of lncRNA NKILA is involved in DC, and overexpression of lncRNA NKILA may serve as a therapeutic target for treating DC.