Deletion of the FHL2 gene attenuates the formation of atherosclerotic lesions after a cholesterol-enriched diet.
OBJECTIVE
FHL2, a member of the four and a half LIM domain (FHL) family of proteins, may play an important role in the circulatory system and in particular atherosclerosis.


METHODS
To investigate the role of FHL2 in atherogenesis, FHL2-null and wild-type control male mice were fed either a normal chow (NC) or a cholesterol-enriched diet (CED).


RESULTS
At 3 months post CED, aortic atherosclerotic plaques were observed in both control and FHL2-null mice. Lesions in control mice increased dramatically by 6 months of CED. In contrast, lesion size did not increase during this time in CED-fed FHL2-null mice. Relative to control mice on a normal chow of diet (NCD), control mice on a CED exhibited lower circulating nitric oxide (NO) levels, and decreased expression of connexin37 (Cx37) and Cx40 in aortic endothelium. In contrast, FHL2-null mice on a CED maintained similar levels of circulating NO as FHL2-null mice fed a NCD. Cxs levels in aortic endothelium of FHL2-null mutants on a NCD were lower relative to control mice on a NCD, and did not decrease with CED.


CONCLUSIONS
Our data demonstrate a role for FHL2 in atherogenesis, the regulation of circular NO release, and expression of gap junctions within aortic endothelium.
Chu
Pao-Hsien
PH
The Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. pchu@adm.cgmh.org.tw
Yeh
Hung-I
HI
Wu
Hsueh-Hua
HH
Hong
Ray-Ching
RC
Shiu
Tzu-Fang
TF
Yang
Chuen-Mao
CM
D000818:Animals; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D017630:Connexins / Q000096:biosynthesis / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D060850:LIM-Homeodomain Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
D002791:Cholesterol, Dietary; D017630:Connexins; C491382:Fhl2 protein, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors; D009569:Nitric Oxide