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

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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.", "claims": [{"id": "claim-method", "statement": "The difference of Western blot data between two groups was analyzed by two-tailed Student’s t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31708766", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "The difference of Western blot data between two groups was analyzed by two-tailed Student’s t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Availability Statement\nThe datasets generated for this study can be found in the proteomics data available via ProteomeXchange with the identifier PXD012306.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31708766", "locator": "sections[21] \"Data Availability Statement\" paragraphs 1-2", "quote": "Data Availability Statement\nThe datasets generated for this study can be found in the proteomics data available via ProteomeXchange with the identifier PXD012306."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31708766"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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