TY  - JOUR
AU  - Arndt, Philipp
AU  - Morton, Lorena
AU  - Briese, Michael
AU  - Lämmlin, Naomi
AU  - Mattern, Hendrik
AU  - Hasanuzzaman, Md
AU  - Westhues, Melina Julia
AU  - Khoshneviszadeh, Mahsima
AU  - Appenzeller, Silke
AU  - Gündel, Daniel
AU  - Toussaint, Magali
AU  - Brust, Peter
AU  - Kniess, Torsten
AU  - Oelschlegel, Anja
AU  - Goldschmidt, Jürgen
AU  - Meuth, Sven
AU  - Müller, Patrick
AU  - Braun-Dullaeus, Rüdiger
AU  - Debska-Vielhaber, Grazyna
AU  - Vielhaber, Stefan
AU  - Becker, Axel
AU  - Dityatev, Alexander
AU  - Henneicke, Solveig
AU  - Sendtner, Michael
AU  - Dunay, Ildiko
AU  - Schreiber, Stefanie
TI  - Vascular and Neural Transcriptomics Reveal Stage-Dependent Pathways to Inflammation and Cognitive Dysfunction in a Rat Model of Hypertension.
JO  - Journal of the American Heart Association
VL  - 15
IS  - 6
SN  - 2047-9980
CY  - New York, NY
PB  - Association
M1  - DZNE-2026-00285
SP  - e040710
PY  - 2026
AB  - Chronic arterial hypertension causes cerebral microvascular dysfunction and increases dementia risk in aging. However, cognitive health preservation by therapeutic blood pressure lowering alone is limited and depends on disease duration, the degree of irreversible tissue damage, and whether microvascular function can be restored. This study aimed to understand molecular and cellular temporospatial mechanisms of disease in the course of hypertension.We investigated the effects of initial, early chronic and late chronic hypertension in the frontal brain of spontaneously hypertensive stroke-prone rats by applying behavioral tests, histopathology, immunofluorescence, fluorescence-activated cell sorting, microvascular/neural tissue RNA sequencing, and 18F-fluorodeoxyglucose positron emission tomography imaging.Chronic hypertension caused behavioral deficits associated with frontal cortex function. Our results highlight stage-dependent responses to continuous microvascular stress and wounding by hypertension. Early chronic responses included a fast recruitment of activated microglia to the blood vessels, immigration of peripheral immune cells, blood-brain barrier breakdown and an energy-demanding hypermetabolic state. Vascular adaptation mechanisms were observed in later stages and included angiogenesis and upregulation of cellular adhesion molecules and extracellular matrix. Among the top upregulated genes in blood vessels, we identified Igfbp-5, which attenuates protective insulin-like growth factor 1 signaling.Our study provides new insight into mechanisms underlying hypertensive pathobiology and highlights its stage-dependent nature. This groundwork will be helpful for basic and clinical research to identify stage-dependent markers in the human disease course, investigate stage-dependent interventions besides blood pressure lowering, and better understand the relationship between poor vascular health and neurodegenerative diseases.
KW  - Animals
KW  - Hypertension: genetics
KW  - Hypertension: complications
KW  - Hypertension: metabolism
KW  - Hypertension: physiopathology
KW  - Disease Models, Animal
KW  - Rats, Inbred SHR
KW  - Transcriptome
KW  - Rats
KW  - Cognitive Dysfunction: genetics
KW  - Cognitive Dysfunction: metabolism
KW  - Cognitive Dysfunction: etiology
KW  - Cognitive Dysfunction: physiopathology
KW  - Male
KW  - Frontal Lobe: metabolism
KW  - Frontal Lobe: blood supply
KW  - Inflammation: genetics
KW  - Inflammation: metabolism
KW  - Behavior, Animal
KW  - Microglia: metabolism
KW  - Blood-Brain Barrier: metabolism
KW  - Blood Pressure
KW  - 18F‐FDG PET (Other)
KW  - RNA sequencing (Other)
KW  - SHRSP (Other)
KW  - cerebral small‐vessel disease (Other)
KW  - hypertension (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41294147
DO  - DOI:10.1161/JAHA.125.040710
UR  - https://pub.dzne.de/record/285728
ER  -