title: Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries.
abstract: The phenotypic and functional changes of coronary arteries with aging promote ischemic heart disease. We hypothesized that these alterations reflect an aging-induced proinflammatory shift in vascular regulatory mechanisms. Thus, in isolated coronary arteries of young (3-month-old) and aged (25-month-old) male Fischer 344 rats the expression of 96 cytokines, chemokines, and their receptors were screened by a cDNA-based microarray technique. In aged vessels expressions of tumor necrosis factor (TNF)-alpha (3.3x), interleukin (IL)-1beta (3.0x), IL-6 (2.9x), IL-6Ralpha (2.8x) and IL-17 (6.1x) genes were significantly increased over young vessels. Quantitative reverse transcriptase-polymerase chain reaction confirmed these results. Western blotting demonstrated that protein expressions of TNF-alpha, IL-1beta, IL-6, and IL-17 were also significantly increased in vessels of aged rats compared with those of young rats. Immunofluorescent double labeling showed that in aged vessels IL-1beta and IL-6 are predominantly localized in the endothelium, whereas TNF-alpha and IL-17 are localized in smooth muscle. Thus, a proinflammatory shift in the profile of vascular cytokine expression may contribute to the aging-induced phenotypic changes in coronary arteries, promoting the development of ischemic heart disease in the elderly.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
authors.forename: John G
authors.initials: JG
authors.lastname: Edwards
authors.forename: Gabor
authors.initials: G
authors.lastname: Kaley
mesh_terms: D000368:Aged; D000375:Aging; D000818:Animals; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger