Age-dependent renal cortical microvascular loss in female mice.
Renal function and blood flow decline during aging in association with a decrease in the number of intrarenal vessels, but if loss of estrogen contributes to this microvascular, rarefaction remains unclear. We tested the hypothesis that the decreased renal microvascular density with age is aggravated by loss of estrogen. Six-month-old female C57/BL6 mice underwent ovariectomy (Ovx) or sham operation and then were allowed to age to 18-22 mo. Another comparable group was replenished with estrogen after Ovx (Ovx+E), while a 6-mo-old group served as young controls. Kidneys were then dissected for evaluation of microvascular density (by micro-computed tomography) and angiogenic and fibrogenic factors. Cortical density of small microvessels (20-200 μm) was decreased in all aged groups compared with young controls (30.3 ± 5.8 vessels/mm², P < 0.05), but tended to be lower in sham compared with Ovx and Ovx+E (9.9 ± 1.7 vs. 17.2 ± 4.2 and 18 ± 3.0 vessels/mm², P = 0.08 and P = 0.02, respectively). Cortical density of larger microvessels (200-500 μm) decreased only in aged sham (P = 0.04 vs. young control), and proangiogenic signaling was attenuated. On the other hand, renal fibrogenic mechanisms were aggravated in aged Ovx compared with aged sham, but blunted in Ovx+E, in association with downregulated transforming growth factor-β signaling and decreased oxidative stress in the kidney. Therefore, aging induced in female mice renal cortical microvascular loss, which was likely not mediated by loss of endogenous estrogen. However, estrogen may play a role in protecting the kidney by decreasing oxidative stress and attenuating mechanisms linked to renal interstitial fibrosis.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
Victor H
VH
Urbieta-Caceres
Farhan A
FA
Syed
Jing
J
Lin
Xiang-Yang
XY
Zhu
Kyra L
KL
Jordan
Caitlin C
CC
Bell
Michael D
MD
Bentley
Amir
A
Lerman
Sundeep
S
Khosla
Lilach O
LO
Lerman
D000302:Adrenal Cortex / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000375:Aging; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005260:Female; D005355:Fibrosis; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects; D017698:Postmenopause; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055114:X-Ray Microtomography
D016212:Transforming Growth Factor beta; D004958:Estradiol; C010452:estradiol-17 beta-benzoate