Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress.
OBJECTIVE
Humanin (HN) is a 24-amino acid peptide that has been shown to have an anti-apoptotic function against neuronal cell death caused by Alzheimer's disease. Increased oxidative stress, one of the major factors contributing to this cell death, also plays an important role in the inflammatory process of atherosclerosis. The current study was designed to test the hypothesis that HN is expressed in the human vascular wall and may protect against oxidative stress.


RESULTS
HN expression in the vascular wall was detected by immunostaining in the endothelial cell layer of human internal mammary arteries (n = 5), atherosclerotic coronary arteries (n = 17), and sections of the greater saphenous vein (n = 3). HN mRNA was expressed in the human aortic endothelial cells (HAECs). Cytoprotective effects of HN against oxidative stress were tested in vitro in HAECs. Pre-treatment with 0.1 µM HN reduced oxidized LDL (Ox-LDL)-induced (i) formation of reactive oxygen species by 50%, (ii) apoptosis by ∼50% as determined by TUNEL staining, and (iii) formation of ceramide, a lipid second messenger involved in the apoptosis signalling cascade, by ∼20%.


CONCLUSIONS
The current study demonstrates for the first time the expression of HN in the endothelial cell layer of human blood vessels. Exogenous addition of HN to endothelial cell cultures was shown to be effective against Ox-LDL-induced apoptosis. These findings suggest that HN may play a role and may have a protective effect in early atherosclerosis in humans.
Bachar
Adi R
AR
Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Scheffer
Lea
L
Schroeder
Andreas S
AS
Nakamura
Hiromi K
HK
Cobb
Laura J
LJ
Oh
Yun K
YK
Lerman
Lilach O
LO
Pagano
Richard E
RE
Cohen
Pinchas
P
Lerman
Amir
A
D000328:Adult; D000368:Aged; D017209:Apoptosis; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008323:Mammary Arteries / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012501:Saphenous Vein / Q000378:metabolism / Q000473:pathology
D002518:Ceramides; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C427211:humanin; C099252:oxidized low density lipoprotein