Atorvastatin Attenuates Myocardial Hypertrophy Induced by Chronic Intermittent Hypoxia In Vitro Partly through miR-31/PKCε Pathway

Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia （CIH）. However, little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy, and whether specific hypertrophyrelated microRNAs are involved in the modulation. MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia. This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy. H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days. The size of cardiomyocytes, and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR, respectively. MiR-31 mimic or Ro 31-8220, a specific inhibitor of protein kinase C epsilon （PKCε）, was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes. PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting. The results showed that CIH induced obvious enlargement of cardiomyocytes, which was paralleled with increased atrial natriuretic peptide （ANP）, brain natriuretic peptide （BNP）, and slow/beta cardiac myosin heavy-chain （MYHT） mRNA levels. All these changes were reversed by the treatment with atorvastatin. Meanwhile, miR-31 was increased by CIH in vitro. Of note, the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31. Moreover, overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes. Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε. These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.

Contact performance analysis of pressure controller's sealing interface in deep in-situ pressure-preserved coring system

The sealing performance of contact interfaces plays the most important role in the design and operation of the in-situ pressure-preserved coring system.To meet the demand of ultra-high pressure-retained coring for oil and gas exploration in deep reservoirs,a quantitative analysis of the contact mechanical behavior of the pressure controller was performed.Based on the micro-contact theory of rough surfaces,a three-dimensional numerical model of the rough contact interface between the valve cover and the valve seat was constructed,and the micro-contact behavior of the metal contact surfaces was comprehensively studied.The results show that the actual contact area of the valve interface increases with the increase of surface roughness before the critical contact point,but decreases after that.Compared with the real contact model with double rough surfaces,although the simplified hard-contact model with a single rough surface can reflect the micro-contact behavior of the rough surface to a certain extent,it cannot truly reveal the microchannel morphology between the sealing interfaces under pressure.Therefore,the realistic double-rough-surface model should be recommended to evaluate the sealing performance of coring tools,particularly for high pressure conditions.The material properties of valves have a significant effect on the contact characteristics of rough surfaces,which suggested that the actual contact area decreases with the increase of the elastic modulus of the contact material under the same loading conditions.The knowledge of this work could help to enhance the seal design of pressure controllers for in-situ pressure-preserved coring.