Expression of alpha smooth muscle actin decreases with ageing and increases upon lumen obstruction in mouse brain pericytes

Győri, Fanni and Mészáros, Ádám and Krecsmarik, Mónika and Molnár, Kinga and Balta, Cornel and Hermenean, Anca and Farkas, Elek Attila and Krizbai, István Adorján and Wilhelm, Imola Mária (2025) Expression of alpha smooth muscle actin decreases with ageing and increases upon lumen obstruction in mouse brain pericytes. GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE), 47 (2). pp. 2525-2540. ISSN 2509-2715

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Abstract

Cerebral pericytes are mural cells covering brain microvessels, organized as ensheathing, mesh and thin-strand pericytes. These latter two, together called capillary pericytes, have low levels of alpha smooth muscle actin (alpha-SMA), regulating basal vascular tone and applying a slow influence on cerebral blood flow. Pericytes are subject to alterations in ageing which may be even more pronounced in age-related pathologies, including microinfarcts, which usually affect a large number of vessels in the ageing brain. We modelled this condition by injecting 10 mu m-size microspheres into the circulation of mice resulting in the occlusion of capillaries covered by ensheathing and mesh pericytes. We observed that alpha-SMA and Acta2, the gene encoding it, as well as TGF-beta 1/Tgfb1, the major regulator of alpha-SMA, decreased during ageing in cerebral microvessels. In the vicinity of the microspheres stalled in the capillaries, expression of alpha-SMA increased significantly in both ensheathing and especially in mesh pericytes, both in young (2 to 3 months of age) and old (24 months of age) mice. On the other hand, gamma-actin was detected in endothelial cells, but not in pericytes, and decreased in microvessels of microsphere-containing hemispheres. Altogether, our data show that obstruction of cerebral microvessels increases alpha-SMA expression in pericytes in both age groups, but this does not compensate for the lower expression of the contractile protein in old animals. Increased alpha-SMA expression may lead to constriction of the obstructed vessels probably aggravating flow heterogeneity in the aged brain.

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