Downregulation of FHL1 expression in thoracic aortic dissection: implications in aortic wall remodeling and pathogenesis of thoracic aortic dissection.
BACKGROUND
To investigate the potential role of four and a half Lin-11, Isl-1, and Mec-3 (FHL1) protein in the pathogenesis of thoracic aortic dissection (TAD).


METHODS
The expression levels and localization of FHL1 protein in aortic tissue of TAD were analyzed using Western blot and immunohistochemistry. Furthermore, small interfering ribonucleic acid was used to knock down the FHL1 gene in rat aortic smooth muscle cells (SMCs). After assessing knockdown efficiency and specificity by real-time polymerase chain reaction and Western blot, the effect of FHL1 knockdown on cell proliferation and apoptosis was evaluated by 3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay and flow cytometry, respectively.


RESULTS
Compared with normal aortic tissue, FHL1 protein expression in aortic tissue from TAD patients was significantly downregulated. Immunohistochemistry analysis showed that FHL1 was mainly localized in the cytoplasm of SMCs. In diseased aortic tissue, FHL1 immunoreactivity was lowest in SMCs in the split aortic media and adjacent area, but relatively high in SMCs in the aortic intima and adventitia. FHL1 knockdown significantly inhibited the proliferation of rat aortic SMCs but exerted no obvious effect on cell apoptosis.


CONCLUSIONS
FHL1 protein expression is downregulated in TAD. Downregulation of FHL1 expression might contribute to the pathogenesis of TAD, perhaps by suppressing the proliferation of aortic SMCs and affecting aortic wall remodeling.
Department of Vascular Surgery, Second Military Medical University, Shanghai, People's Republic of China.
Jianfeng
J
Weng
Mingfang
M
Liao
Sili
S
Zou
Junmin
J
Bao
Jian
J
Zhou
Lefeng
L
Qu
Rui
R
Feng
Xiang
X
Feng
Zhiqing
Z
Zhao
Zaiping
Z
Jing
D000328:Adult; D000784:Aortic Dissection / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D060588:LIM Domain Proteins; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
C101149:FHL1 protein, human; C517184:Fhl1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins