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@ARTICLE{Morton:275866,
      author       = {Morton, Lorena and Garza, Alejandra P and Debska-Vielhaber,
                      Grazyna and Villafuerte, Luis E and Henneicke, Solveig and
                      Ulbrich, Philipp and Meuth, Sven G and Schreiber, Stefanie
                      and Dunay, Ildiko R},
      title        = {{P}ericytes and {E}xtracellular {V}esicle {I}nteractions in
                      {N}eurovascular {A}daptation to {C}hronic {A}rterial
                      {H}ypertension.},
      journal      = {Journal of the American Heart Association},
      volume       = {14},
      number       = {1},
      issn         = {2047-9980},
      address      = {New York, NY},
      publisher    = {Association},
      reportid     = {DZNE-2025-00101},
      pages        = {e038457},
      year         = {2025},
      abstract     = {Chronic arterial hypertension restructures the vascular
                      architecture of the brain, leading to a series of
                      pathological responses that culminate in cerebral
                      small-vessel disease. Pericytes respond dynamically to
                      vascular challenges; however, how they manifest under the
                      continuous strain of hypertension has not been elucidated.In
                      this study, we characterized pericyte behavior alongside
                      hypertensive states in the spontaneously hypertensive
                      stroke-prone rat model, focusing on their phenotypic and
                      metabolic transformation. Flow cytometry was used to
                      characterize pericytes by their expression of
                      platelet-derived growth factor receptor β, neuroglial
                      antigen 2, cluster of differentiation 13-alanyl
                      aminopeptidase, and antigen Kiel 67. Microvessels were
                      isolated for gene expression profiling and in vitro pericyte
                      expansion. Immunofluorescence validated the cell culture
                      model. Plasma-derived extracellular vesicles from
                      hypertensive rodents were applied as a treatment to assess
                      their effects on pericyte function and detailed metabolic
                      assessments on enriched pericytes measured oxidative
                      phosphorylation and glycolysis. Our results reveal a shift
                      in platelet-derived growth factor receptor β+ pericytes
                      toward increased neuroglial antigen 2 and cluster of
                      differentiation 13-alanyl aminopeptidase coexpression,
                      indicative of their critical role in vascular stabilization
                      and inflammatory responses within the hypertensive milieu.
                      Significant alterations were found within key pathways
                      including angiogenesis, blood-brain barrier integrity,
                      hypoxia, and inflammation. Circulating extracellular
                      vesicles from hypertensive rodents distinctly influenced
                      pericyte mitochondrial function, evidencing their dual role
                      as carriers of disease pathology and potential therapeutic
                      agents. Furthermore, a shift toward glycolytic metabolism in
                      hypertensive pericytes was confirmed, coupled with ATP
                      production dysregulation.Our findings demonstrate that
                      cerebral pericytes undergo phenotypic and metabolic
                      reprogramming in response to hypertension, with
                      hypertensive-derived plasma-derived extracellular vesicles
                      impairing their mitochondrial function. Importantly,
                      plasma-derived extracellular vesicles from normotensive
                      controls restore this function, suggesting their potential
                      as both therapeutic agents and precision biomarkers for
                      hypertensive vascular complications. Further investigation
                      into plasma-derived extracellular vesicle cargo is essential
                      to further explore their therapeutic potential in vascular
                      health.},
      keywords     = {Pericytes: metabolism / Pericytes: pathology / Animals /
                      Extracellular Vesicles: metabolism / Hypertension:
                      physiopathology / Hypertension: metabolism / Rats, Inbred
                      SHR / Male / Rats / Disease Models, Animal / Chronic Disease
                      / Cells, Cultured / Adaptation, Physiological / Blood-Brain
                      Barrier: metabolism / Blood-Brain Barrier: pathology /
                      blood–brain barrier (Other) / extracellular vesicles
                      (Other) / hypertension (Other) / mitochondrial membrane
                      potential (Other) / pericytes (Other) / spontaneously
                      hypertensive stroke‐prone rat (SHRSP) (Other) / vascular
                      remodeling (Other)},
      cin          = {AG Schreiber},
      ddc          = {610},
      cid          = {I:(DE-2719)1310010},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39719419},
      doi          = {10.1161/JAHA.124.038457},
      url          = {https://pub.dzne.de/record/275866},
}