The Role Of Klf2and PAR-1in Vulnerable Plaques Of Apoe-/-Mice And The Intervention Of Statin

Objectives:To explore the function of kruppel-like factor2(KLF2) and protease-activated receptor-1(PAR-1) in the vulnerable plaque of atherosclerosis, and to study the intervention of statin.Methods:Seventy two ApoE gene knock out (ApoE-'-) mice were randomized into a high fat-diet group and a normal-diet control group, an early high fat-diet control group, an early low-dosage intervention group, an early high-dosage intervention group, a late high fat-diet control group, a late low-dosage intervention group, and late high-dosage intervention group. Nice mice were assigned to each group. Mice model of atherosclerosis was built successfully. After intervented by atorvastatin, the aortic arch of ApoE-/-mice was made into paraffin sections, and then followed by haematoxylin and eosin staining. The degree of atherosclerotic positive remodeling was calculated on H&E slides. The vulnerability of atherosclerotic plaques was accessed by mesuring the ratio of the fibrous cap thickness to the tunica intima/media thickness (FCT/IMT) and the vulnerable index [VI=(machophages+lipid poor)/(SMCs+collagens)]. Meanwhile, the mRNA, protein and histology expressions of KLF2and PAR-1from regional tissue were determined by RT-PCR, western blot and immunohistochemistry in the aorta of ApoE-/-mice. Data were compared following stadard statistics.Results:1. ApoE-/-mice model of atherosclerosis was built successfully. Compared with the normal-diet control group, a larger plaque area (P<0.05) and a less plaque stablility (P<0.05) was observed in the high fat-diet group.2. For both mRNA (P<0.05) and protein expression (P<0.01), KLF2increased while PAR-1decreased in the group labeled as vulnerable group.3. The plaque area in the mice aorta was negatively correlated to KLF2expression(r=-0.711, P<0.01) and positively correlated to PAR-1expression(r=0.839, P<0.01). The stability of plaque (FCT/IMT) was positively correlated to KLF2expression(r=0.890, P<0.01), and negatively correlated to PAR-1expresion (r=-0.837, P<0.01)。4. KLF2expression was increased and PAR-1was decreased by atovastatin(P<0.01). KLF2or PAR-1expression was time-dependent and dosage-dependent to the statin intervention (P<0.01).Conclusions:1. The up-regulation of KLF2and the down-regulation of PAR-1may participate in the occurrence and development of vulnerable plaque.2. Atorvastatin up-regulates KLF2and down-regulates PAR-1expression, and this may be one of mechanisms that underlie the plaque stabilization effect by statin.