ABSTRACT
Objective: To observe the expression of transient receptor potential channel-1—large conductance Ca2+-activated K+channel (TRPC1-BK) signal complex in aortic smooth muscle tissue in experimental mice of atherosclerosis (AS). Methods: Our research included in 2 groups: Control group, wild C57BL/6J mice were fed by normal diet and AS group, ApoE-/- mice were fed by high fat diet to establish AS model. All animals were treated for 10 weeks, n=10 in each group. The total RNA and protein were extracted from aortic smooth muscle tissue in sacrificed mice. The mRNA and protein expressions of TRPC1, BKα and BKβ1 subunit were measured by RT-PCR, Western blot analysis and immunohistochemistry staining. Results: By RT-PCR examination, compared with Control group, AS group showed increased mRNA expression of TRPC1, P<0.05 and decreased mRNA expressions of BKα and BKβ1 subunit, both P<0.01. By Western blot analysis, compared with Control group, AS group had elevated protein expression of TRPC1, P<0.05 and reduced protein expressions of BKα and BKβ1 subunit, both P<0.01; by immunohistochemistry staining, AS group had the higher protein expression of TRPC1, P<0.01 and the lower protein expressions of BKα and BKβ1 subunit, both P<0.05. Conclusion: The mRNA and protein expressions of TRPC1-BK signal complex were affected in aortic smooth muscle tissue in AS mice, which speculated that TRPC1-BK signal complex might be become a new target for treating the relevant vascular disease.
ABSTRACT
Objective In this research we established rapid atrial pacing rabbit models, to investigate the effects of simvastatin on changes of early atrial effective refractory period (AERP) and protein expression of atrial α1c sub-unit of L-type calcium channel on atrial remodeling. Methods 42 rabbits were randomly divided into 3 groups:control group,rapid pacing group and simvastatin group,simvastatin 5 mg/( kg·d) was given intragastrically daily for two weeks before electrophysiology study in simvastatin group, normal saline was given intragastrically in control and rapid pacing group instead. Control group with no pacing, in simvastatin group and rapid pacing group, right atrium was paced at 800 beats/min for 8 hours to establish acute atrial fibrillation models, right atrial effective re-fractory period(AERP)was measured at the basic cycle length of 200 ms and 150 ms before pacing and 1,2,4,6, and 8 hours after the onset of the pacing, the changes of rate adaptation of AERP (AERP200-AERP150) were ana-lyzed . Right atrium tissue was obtained for measurement of protein expression of atrialα1 c subunit of L-type calcium channel by Western blot. Simultaneously,lipid levels in each group was examined. Results No significant differ-ence in lipid levels among three groups was observed. The AERP was shortened and the rate adaptation of AERP (AERP200-AERP150) disappeared during pacing compared with those before pacing(P<0.05). The shortening of AERP was reversed and AERP200-AERP150 was maintained in simvastatin group. Compared with the control group,the protein expression levels of atrial α1c subunit of L-type calcium channel decreased significantly after 8 hours pacing in rapid pacing group(P<0.01). The protein expression levels of simvastatin group decreased insig-nificantly . Conclusion Atrial rapid pacing can induce the shortening of the AERP and the losing of adaptability to the frequency of AERP,pretreatment with simvastatin can improve the degree significantly and maintain the adapta-bility to frequence basically. The protein expression levels of atrial α1c subunit of L-type calcium channel de-creased significantly after 8 hours pacing,pretreatment with simvastatin can prevent this change without lowering the lipid levels,thus contributing to the ionic mechanism of simvastatin for antiarrhythmia.