title: Aging differentially alters the expression of angiogenic genes in a tissue-dependent manner.
abstract: Organ functions are altered and impaired during aging, thereby resulting in increased morbidity of age-related diseases such as Alzheimer's disease, diabetes, and heart failure in the elderly. Angiogenesis plays a crucial role in the maintenance of tissue homeostasis, and aging is known to reduce the angiogenic capacity in many tissues. Here, we report the differential effects of aging on the expression of angiogenic factors in different tissues, representing a potentially causes for age-related metabolic disorders. PCR-array analysis revealed that many of angiogenic genes were down-regulated in the white adipose tissue (WAT) of aged mice, whereas they were largely up-regulated in the skeletal muscle (SM) of aged mice compared to that in young mice. Consistently, blood vessel density was substantially reduced and hypoxia was exacerbated in WAT of aged mice compared to that in young mice. In contrast, blood vessel density in SM of aged mice was well preserved and was not different from that in young mice. Moreover, we identified that endoplasmic reticulum (ER) stress was strongly induced in both WAT and SM during aging in vivo. We also found that ER stress significantly reduced the expression of angiogenic genes in 3T3-L1 adipocytes, whereas it increased their expression in C2C12 myotubes in vitro. These results collectively indicate that aging differentially affects the expression of angiogenic genes in different tissues, and that aging-associated down-regulation of angiogenic genes in WAT, at least in part through ER stress, is potentially involved in the age-related adipose tissue dysfunction.
authors.affiliation: Department of Cardiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii, Kawaramachi-Hirokoji, Kamigyo, Kyoto 602-8566, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: Department of Cardiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii, Kawaramachi-Hirokoji, Kamigyo, Kyoto 602-8566, Japan.
authors.forename: Kiyonari
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Cardiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii, Kawaramachi-Hirokoji, Kamigyo, Kyoto 602-8566, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ono
authors.affiliation: Department of Cardiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii, Kawaramachi-Hirokoji, Kamigyo, Kyoto 602-8566, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Soma
authors.affiliation: Department of Cardiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii, Kawaramachi-Hirokoji, Kamigyo, Kyoto 602-8566, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ueyama
authors.affiliation: Department of Cardiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii, Kawaramachi-Hirokoji, Kamigyo, Kyoto 602-8566, Japan.
authors.forename: Satoaki
authors.initials: S
authors.lastname: Matoba
authors.affiliation: Department of Cardiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii, Kawaramachi-Hirokoji, Kamigyo, Kyoto 602-8566, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Cardiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii, Kawaramachi-Hirokoji, Kamigyo, Kyoto 602-8566, Japan. Electronic address: ikedak@koto.kpu-m.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D041721:3T3-L1 Cells; D052436:Adipose Tissue, White / Q000098:blood supply* / Q000502:physiology*; D000375:Aging; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D018919:Neovascularization, Physiologic
chemical_list: D043925:Angiogenesis Inducing Agents
keywords: Age-related disease; Aging; Angiogenesis; Metabolic disorder; White adipose tissue