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Hypertension-induced neurovascular and cognitive dysfunction at single-cell resolution.

Samantha M Schaeffer1, Anthony G Pacholko1, Monica M Santisteban1

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Summary

High blood pressure (hypertension) early damages brain cells like endothelial cells and neurons, leading to cognitive impairment. This study reveals the molecular basis for these hypertension-induced brain changes.

Keywords:
angiotensin-IIneural network dysfunctionneurovascular couplingnitric oxideoligodendrocytesenescencesingle-cell RNA sequencingvascular remodelingwhite matter disease

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Area of Science:

  • Neuroscience
  • Cardiovascular Science
  • Genomics

Background:

  • Hypertension is a major cause of cognitive impairment.
  • The precise cellular mechanisms by which hypertension affects the brain are not fully understood.
  • Angiotensin II plays a role in human hypertension and cerebrovascular changes.

Purpose of the Study:

  • To investigate the transcriptomic changes in the neocortex of a mouse model of hypertension.
  • To identify early cellular vulnerabilities and molecular pathways affected by hypertension.
  • To understand the progression of neurovascular and cognitive deficits.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) was employed in a mouse model of angiotensin II-induced hypertension.
  • Transcriptomic profiles were analyzed at early (3 days) and later (42 days) time points relative to deficit onset.
  • Cellular changes were correlated with neurovascular and cognitive outcomes.

Main Results:

  • Early hypertension (3 days) induced endothelial cell transport disruption and senescence, stalled oligodendrocyte differentiation, and interneuronal hypofunction.
  • These early changes were linked to angiotensin II signaling.
  • Later hypertension (42 days) showed deficits in myelination, axonal conduction, and neuronal mitochondrial dysfunction, coinciding with cognitive impairment.

Conclusions:

  • Hypertension causes early, previously unrecognized vulnerability in endothelial cells, interneurons, and oligodendrocytes.
  • These early cellular changes provide a molecular basis for later neurovascular dysfunction and cognitive impairment.
  • The study offers valuable data for future research into hypertension-related brain damage and therapeutic targets.