The Role Of FIZZ1 In Atherosclerosis Progression And The Potential Mechanism

Atherosclerosis(AS) takes the first place of the human killers since it leads to massive cardiovascular and cerebrovascular diseases. A number of profound studies have been made on the pathogenesis of AS by many researchers, but the fatality of cardiovascular and cerebrovascular diseases remain still high, which may be due to the doubt on the pathogenesis of AS.FIZZ1(found in inflammatory zone 1), a novel factor which was found in 2000, was significantly upregulated by hypoxia and inflammation in circulating monocytes and activated macrophages. It was observed that FIZZ1 participated in the development of hypoxic pulmonary vascular remodeling by stimulating pulmonary vascular smooth muscle cells(VSMCs) proliferation and migration. It is known that hypoxia and inflammation coexist during the development of atherosclerosis and there are many activated macrophages in atherosclerosis lesions. Therefore, We hypothesized that the expression of FIZZ1 was upregulated in atherosclerosis lesions and FIZZ1 participated in the process of atherosclerosis.In this study, an atherosclerosis model of apoE-knockout mouse was established. The expression of FIZZ1 was observed by immunohistochemistry and RT-PCR. We tested the proliferative and migrative role of FIZZ1 in cultured mouse vascular smooth muscle cells with recombinant FIZZ1. To provide new avenues for the prevention and treatment of atherosclerosis, the potential signal transduction pathway was also studied.Our main findings and conclusions were as follows:1. The hs-CRP level in AS group and rosiglitazone group is significantly higher than that in normal control group. Rosiglitazone could significantly decrease the serum hs-CRP level.2. Histomorphometric analysis showed that there were significant atherosclerosis plaques in the mice aortas of AS group and rosiglitazone group. And the area of atherosclerosis lesions in rosiglitazone group was significantly smaller than that in AS group. It showed that rosiglitazone could suppress the progression of atherosclerosis.