Effect Of Atorvastatin On PPARγand GlUT4 Expression In Hypertrophic Myocardium Of Spontaneously Hypertensive Rats

Background and Objective: Hypertension is a common cardiovasculardiseases. Sustained hypertension cause damage to target organs, includingheart, brain and kidney. Left ventricular hypertrophy is the majormanifestation of cardiac damage, and is the major risk factor ofcardiovascular events and sudden cardiac death in patients with hypertension.Recently studies have shown that alterations in cardiac energy metabolism toadapt increasing cardiac work have been implicated in the pathogenesis tothe development of myocardial hypertrophy. Inhibits the myocardialhypertrophy has been a new target in addition to controlling arterial pressurein hypertension treatment, and improve cardiomyocyte metabolism may beone way for it. PPARγas a central regulator of adipocyte differentiation andlipid metabolism, GLUT4 as an important mediator of cardiac glucosemetabolism, play an important role in the development of myocardialhypertrophy. Statins have run a protective effect on cardiovascular systemindependently of its lipid metabolism effect. Recent studies show that statinscan inhibit myocardial hypertrophy by controlling the synthesis of intermediate of isoprene, blocking the synthesis of collagen, and having theaction of anti-inflammation and anti-oxidation. But, the relationship betweenstatins and metabolism gene (PPARγ, GLUT4) is not very clear. Thepurposes of this study is to investigate the effect of atorvastatin (ATV) on theexpression of PPARγand GLUT4 in myocardial tissue of SHR and toresearch the possible mechanisms to inhibits the myocardial hypertrophy,which may provide a new idea in hypertension treatment.Methods: Sixteen male 8-week-old SHR were randomly divided intotwo groups: SHR-controlled group (SHR group, n=8) andatorvastatin-treated group (ATV group, n=8). Eight age-matchedWistar-Kyoto rats as normal control (WKY group, n=8). ATV group: ratswere given atorvastatin which was resolved in distilled water 50mg·kg-1·d-1for 10 weeks. SHR group and WKY group: rats were given the same volumeof distilled water for 10 weeks. After 10 weeks (1) The fasting serum lipidwere measured; (2)Body weight (BW), heart weight (HW) and left ventricleweight (LVW) were measured. The heart weight to body weight ratio(HW/BW) and the left ventricle weight to body weight ratio (LVW/BW)were calculated as an index for myocardial hypertrophy;(3)Histomorphology of the rats’myocardial tissue were observed afterHE-staining; (4)The distribution of the PPARγand GLUT4 protein in cardiomyocyte was observed by immunohistochemistry analysis; (5)Theexpression of PPARγand GLUT4 mRNA in myocardial tissue wereevaluated by RT-PCR method.Result：1. Result of serum lipid: SHR group and ATV group had significantlylower serum TC, TG, HDL-C and LDL-C levels compared with WKY group(p<0.05). However, there was no difference in serum TC, TG, HDL-C andLDL-C levels between SHR group and ATV group (p>0.05).2. Myocardial hypertrophy index: HW/BW and LVW/BW weresignificantly higher in SHR group and ATV group compared with WKYgroup (p<0.05), and decreased in ATV group compared with SHR group(p<0.05).3. Histomorphology of the myocardial tissue: in WKY group, thecardiomyocyte had normally size, regularly morphologies and orderliness. InSHR group, the cardiomyocyte had large size, irregularly morphologies,disarranged in rows, and a part of myocardial fibers were broken. In ATVgroup that was found between the two.4. Immunohistochemistry detection: the expression of PPARγproteinin cardiomyocyte were lower in SHR group and ATV group compared withWKY group(p<0.05)，and increased in ATV group compared with the SHR group (p<0.05). Positive GLUT4 protein staining in cardiomyocyte wasstrong in WKY group and weak in SHR group, and which was found in themiddle in ATV group.5. RT-PCR detection: the expression of PPARγand GLUT4 mRNA inmyocardial tissue were statistically lower in SHR group and ATV groupcompared with WKY group(p<0.05)，and increased in ATV group comparedwith SHR group (p<0.05).6. The association between the expression of PPARγin myocardialtissue and myocardial hypertrophy: the expression of PPARγmRNA inmyocardial tissue was negatively correlated with myocardial hypertrophyindex（with HW/BW, r=-0.858, P<0.0001; with LVW/BW, r=-0.901,P<0.0001).Conclusion：Atorvastatin upregulate the expression of PPARγandGLUT4 in myocardial tissue, whch mght be one of the possible mechanismsof atorvastatin to inhibit the myocardial hypertrophy of hypertension.