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Proteome Profiling of Cerebral Vessels in Rhesus Macaques: Dysregulation of Antioxidant Activity and Extracellular Matrix Proteins Contributes to Cerebrovascular Aging in Rhesus Macaques

Authors
  • Wang, Xia1
  • Liu, Yifan1
  • Jia, Yangjie1
  • Liu, Haotian1
  • Bao, Xinjie2
  • He, Zhanlong3
  • Ge, Wei1, 4
  • 1 State Key Laboratory of Medical Molecular Biology, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing , (China)
  • 2 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing , (China)
  • 3 Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Disease, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming , (China)
  • 4 Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding , (China)
Type
Published Article
Journal
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Publication Date
Oct 23, 2019
Volume
11
Identifiers
DOI: 10.3389/fnagi.2019.00293
Source
Frontiers
Keywords
Disciplines
  • Neuroscience
  • Original Research
License
Green

Abstract

Aging is a major risk factor for cerebrovascular disease; however, the molecular mechanisms of cerebrovascular aging remain to be clarified. The aim of this study was to reveal the molecular signaling pathways involved in cerebrovascular aging. This study used high-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with quantitative 6-plex tandem mass tag labeling, to profile protein changes in brain vessels from three groups of healthy rhesus macaques (3-years, 6-years, and 20-years). Western blot analyses were used to validate the proteomic data. A total of 2,934 proteins were identified and analyzed. Twenty-two proteins were continuously downregulated with increasing age, while three proteins were continuously upregulated. When comparing Group C vs. Group B, 270 proteins were downregulated, while 73 proteins were upregulated. All these 368 significantly changed proteins were used for further analysis. Bioinformatic analysis showed that the changed proteins were involved in several signaling pathways during cerebrovascular aging. Proteins in the NRF2 pathway, such as Glutathione S-transferase Mu (GSTM), were consistently downregulated especially after 6-years old, whereas proteins related to miRNA targets in the extracellular matrix (ECM) and membrane receptors were upregulated. Protein-protein interaction networks demonstrated that disorders of energy pathways and serine/threonine kinases were critical during cerebrovascular aging. Data are available via ProteomeXchange under the identifier PXD012306. Our results indicated that during aging, the disorders of energy metabolism and dysfunction of antioxidant activity caused over-production of reactive oxygen species (ROS) may exacerbate cerebrovascular aging. In addition, accumulation of ECM proteins during aging might be closely associated with age-related arterial stiffening and decreased compliance.

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