Proinflammatory profile within the grossly normal aged human aortic wall.
Studies in animal models demonstrate that angiotensin II and its downstream signaling molecules, that is, matrix metalloproteinases and monocyte chemoattractant protein-1, increase within the diffusely thickened intima of central arteries with aging. Whether such age-related changes occur within the human arterial wall is unknown. We harvested "grossly normal thoracic aortas" from 5 young (20+/-3 years) and 5 old white males (65+/-6 years) at necropsy, after death from traumatic causes. The intimae of older samples were markedly and diffusely thickened compared with younger intimae and contained increased levels of angiotensin-converting enzyme, angiotensin II, angiotensin II receptor type 1, matrix metalloproteinases 2/9, monocyte chemoattractant protein-1, and collagen I and III proteins. In situ activities of metalloproteinases 2/9 were also significantly enhanced within old, normal aortas. The thickened intima of older aortas also contained a 5-fold increase in the embryonic form of smooth muscle myosin heavy chain-labeled cells than that of younger aortas, and these fetal-type cells were colocalized with angiotensin II protein staining. The ability of isolated smooth muscle cells to invade an artificial basement membrane in response to a monocyte chemoattractant protein-1 gradient increased with age. Furthermore, angiotensin II increased the invasive capacity of young smooth muscle cells, and this effect was reduced by a metalloproteinase inhibitor or an angiotensin II receptor blocker. Thus, in the absence of lipid infiltration, the aged human aortic wall exhibits a proinflammatory profile that renders it a fertile substrate for the development of arterial disease, for example, atherosclerosis and hypertension.
Wang
Mingyi
M
National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA. mingyiw@grc.nia.nih.gov
Zhang
Jing
J
Jiang
Li-Qun
LQ
Spinetti
Gaia
G
Pintus
Gianfranco
G
Monticone
Robert
R
Kolodgie
Frank D
FD
Virmani
Renu
R
Lakatta
Edward G
EG
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D012016:Reference Values; D012084:Renin-Angiotensin System; D017539:Tunica Intima / Q000502:physiology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009218:Myosins