Vasa vasorum lumen narrowing in brain vascular hyalinosis in systemic hypertension patients with ischemic stroke
Sergiy G. Gychka,
Nataliia V. Shults,
Sofia I. Nikolaienko,
Nurefsan E. Sariipek,
Tatiana A. Malysheva,
Vyacheslav A. Dibrova,
Yuichiro J. Suzuki,
Alexander S. Gavrish
Posted 17 Oct 2020
bioRxiv DOI: 10.1101/2020.10.16.342741
Posted 17 Oct 2020
Ischemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the lumen of the brain vasculature contributes to the increased incidence of stroke. While hyalinosis represents the major pathological lesions contributing to the vascular lumen narrowing and stroke, the pathogenic mechanism of brain vascular hyalinosis has not been well characterized. Thus, the present study examined the postmortem brain vasculature of human patients who died of ischemic stroke due to systemic hypertension. Hematoxylin and eosin staining and immunohistochemistry showed the occurrence of brain vascular hyalinosis with infiltrated plasma proteins along with the narrowing of vasa vasorum and oxidative stress. Transmission electron microscopy revealed the endothelial cell bulge protrusion into the vasa vasorum lumen and the occurrence of endocytosis in the vasa vasorum endothelium. The treatment of cultured microvascular endothelial cells with adrenaline also promoted the formation of the bulge as well as endocytic vesicles. siRNA knockdown of sortin nexin-9 (a mediator of clathrin-mediated endocytosis) inhibited the adrenaline-induced endothelial cell bulge formation. Adrenaline promoted protein-protein interactions between sortin nexin-9 and neural Wiskott-Aldrich Syndrome protein (a regulator of actin polymerization). We propose that endocytosis-depending endothelial cell bulge narrows the vasa vasorum, resulting in ischemic oxidative damage to the cerebral vessels, the formation of hyalinosis, the occurrence of ischemic stroke, and death in systemic hypertension patients. ### Competing Interest Statement The authors have declared no competing interest.
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