Inflammatory pathways are central to posterior cerebrovascular artery remodelling prior to the onset of congenital hypertension

• Published in: Journal of cerebral blood flow and metabolism Vol. 39; no. 9; pp. 1803 - 1817
• Main Authors: Walas, Dawid, Nowicki-Osuch, Karol, Alibhai, Dominic, von Linstow Roloff, Eva, Coghill, Jane, Waterfall, Christy, Paton, Julian FR
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.09.2019
• Subjects: Animals; Cerebral Arteries - metabolism; Cerebral Arteries - physiopathology; Cerebrovascular Circulation; Hypertension - complications; Hypertension - congenital; Hypertension - genetics; Hypertension - physiopathology; Inflammation - complications; Inflammation - genetics; Inflammation - physiopathology; Male; Original; Rats; Stroke - etiology; Stroke - genetics; Stroke - physiopathology; Transcriptional Activation; Transcriptome; fluorescent microscopy; Cerebrovascular remodelling; transcriptomic plasticity; inflammatory pathways; genetic hypertension
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X18769180

Cerebral artery hypoperfusion may provide the basis for linking ischemic stroke with hypertension. Brain hypoperfusion may induce hypertension that may serve as an auto-protective mechanism to prevent ischemic stroke. We hypothesised that hypertension is caused by remodelling of the cerebral arteries, which is triggered by inflammation. We used a congenital rat model of hypertension and examined age-related changes in gene expression of the cerebral arteries using RNA sequencing. Prior to hypertension, we found changes in signalling pathways associated with the immune system and fibrosis. Validation studies using second harmonics generation microscopy revealed upregulation of collagen type I and IV in both tunica externa and media. These changes in the extracellular matrix of cerebral arteries pre-empted hypertension accounting for their increased stiffness and resistance, both potentially conducive to stroke. These data indicate that inflammatory driven cerebral artery remodelling occurs prior to the onset of hypertension and may be a trigger elevating systemic blood pressure in genetically programmed hypertension.