TY  - JOUR
AU  - Morton, Lorena
AU  - Garza, Alejandra P
AU  - Debska-Vielhaber, Grazyna
AU  - Villafuerte, Luis E
AU  - Henneicke, Solveig
AU  - Ulbrich, Philipp
AU  - Meuth, Sven G
AU  - Schreiber, Stefanie
AU  - Dunay, Ildiko R
TI  - Pericytes and Extracellular Vesicle Interactions in Neurovascular Adaptation to Chronic Arterial Hypertension.
JO  - Journal of the American Heart Association
VL  - 14
IS  - 1
SN  - 2047-9980
CY  - New York, NY
PB  - Association
M1  - DZNE-2025-00101
SP  - e038457
PY  - 2025
AB  - 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.
KW  - Pericytes: metabolism
KW  - Pericytes: pathology
KW  - Animals
KW  - Extracellular Vesicles: metabolism
KW  - Hypertension: physiopathology
KW  - Hypertension: metabolism
KW  - Rats, Inbred SHR
KW  - Male
KW  - Rats
KW  - Disease Models, Animal
KW  - Chronic Disease
KW  - Cells, Cultured
KW  - Adaptation, Physiological
KW  - Blood-Brain Barrier: metabolism
KW  - Blood-Brain Barrier: pathology
KW  - blood–brain barrier (Other)
KW  - extracellular vesicles (Other)
KW  - hypertension (Other)
KW  - mitochondrial membrane potential (Other)
KW  - pericytes (Other)
KW  - spontaneously hypertensive stroke‐prone rat (SHRSP) (Other)
KW  - vascular remodeling (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39719419
DO  - DOI:10.1161/JAHA.124.038457
UR  - https://pub.dzne.de/record/275866
ER  -