Endothelial nitric oxide synthase stimulates aneurysm growth in aged mice.
OBJECTIVE
Age-associated changes in endothelial nitric oxide synthase (eNOS) expression have not been definitively linked to the pathophysiology of aortic aneurysms. We examined the role of eNOS in human patients and an age-appropriate mouse model.


METHODS
eNOS transcripts and immunodetectable protein were assessed by quantitative PCR and immunohistochemistry in human ascending thoracic aneurysms (n = 29) and referent aortae (n = 31). Carotid aneurysms were induced with CaCl2 in young adult (3 months) and aged (18 months) C57BL/6 and eNOS-knockout (eNOS-KO) mice.


RESULTS
eNOS transcripts and protein were reduced in human aneurysms compared with controls, although aortic eNOS expression also decreased with patient age. Aged wild-type mice had significantly larger aneurysm diameter than young adult mice. Aged wild-type mice had reduced eNOS transcripts and protein compared with young adult mice. Aged eNOS-KO mice had smaller aneurysms compared with aged wild-type mice but similar size aneurysms compared with young eNOS-KO and young wild-type mice.


CONCLUSIONS
eNOS expression is reduced in both aged human and aged mouse endothelium and eNOS expression is linked to aneurysm expansion in aged but not young adult mice. These findings support the relevance of age-associated changes in eNOS expression in clinical aneurysmal disease.
Pimiento
Jose M
JM
Department of Surgery, Yale University School of Medicine, New Haven, Conn 06520-8089, USA.
Maloney
Stephen P
SP
Tang
Paul C Y
PC
Muto
Akihito
A
Westvik
Tormod S
TS
Fitzgerald
Tamara N
TN
Fancher
Tiffany T
TT
Tellides
George
G
Dardik
Alan
A
D000328:Adult; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000378:metabolism; D001014:Aortic Aneurysm / Q000201:enzymology; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D002532:Intracranial Aneurysm / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D052250:Nitric Oxide Synthase Type III