The Effect Of Atorvastatin On The Expression Of Peroxisome Proliferator Activated Receptor Gamma (PPARγ) In Human Peripheral Blood Monocytes Of Acute Coronary Syndrome(ACS)

Background and Objective It is widely recognized that atherosclerosis is a specific example of a chronic inflammatory disease. Peroxisome Proliferator Activated Receptor Gamma (PPARγ) is a kind of nuclear hormone receptor,which play most important roles in regulation of metablism. Some studies indicated that activation of PPARγcould lead to reduction in atherosclerosis by decreasing inflammatory responses. Anti-inflammatory effects of statins contribute to their clinical benefit. Molecular mechanisms underlying these effects have not been well explored. We hypothesized that part of this anti-inflammation effects are mediated by activation of PPARγ.Methods 159 persons (35 normal persons and 124 patients with ACS) were investigated. Patients with ACS were randomized to either atorvastatin 10mg/d or atorvastatin 40mg/d in addition to their routine anti-anginal treatment. Serum level of HsCRP, blood lipids and expression of PPARγin peripheral blood monocytes were measured before and after one week treatment.Expression of PPARγwere quantified via flow-cytometry. PPARγexpression in monocytes after incubation with atorvastatin for 24 hours were quantitative via RT-PCR.Results Our studies indicated that PPARγexpressed in peripheral blood monocytes of normal subjects and patients with ACS. Compared with normal subjects, patients with ACS had higher level of serum HsCRP (8.07±0.51 versus 2.99±0.15mg/L, respectively;p<0.05) and lower PPARγexpression in monocytes (1.15±0.43 versus 5.93±0.54, respectively;p<0.05). Expression of PPARγin patients with AMI was lower than that in patientswith unstable angina.(0.51±0.42 versus 3.13±0.88, respectively;p<0.01 ). Serum level of hsCRP in patients with AMI was higher than that in patients with UA(16.07±0.86 versus 5.21±0.72mg/L, respectively;p<0.01). PPARγexpression in monocyte increased and serum hsCRP decreased after treatment. The effect of atorvastatin 40mg/d on PPARγand hsCRP was more effective than that of atorvastatin 10mg/d( PPARγ: 3.38±0.12 versus 0.51±0.02 , respectively;P<0.01 ; HsCRP : 11.45±2.14 versus 1.00±2.25mg/L, respectively; p<0.01).In vitro studies, PPARγexpression in monocytes after incubation with atorvastatin for 24 hours was significantly increased(0.68±0.17 versus 0.56±0.02,respectively; p<0.01), this effect could be reversed by mevalonate.Conclusion 1.Both normal subjects and patients with ACS have expression of PPARγin monocytes.The PPARγexpression in normal subjects is higher than that people with ACS. 2.The PPARγexpression decrease with the aggravation of ACS.3.Atorvastation improve the level of PPARγexpression. The effect of atorvastatin 40mg/d on PPARγis more effective than that of atorvastatin 10mg/d.Atorvastatin influence the expression of PPARγvia inhibition of mevalonate.4.Atorvastation can significantly decrease the serum leves of HsCRP in patient with ACS, which means it has anti-inflammatory effect. Our investigations imply part of this anti-inflammatory effects may be mediated by activation of PPARγ.