English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Smooth muscle cell contraction is an essential function of arteries and relies on the integrity of the actin-myosin apparatus. The tissue-specific α2-smooth muscle actin, encoded by  ACTA2 , is predominantly expressed in vascular smooth muscle cells.  ACTA2  mutations predispose to development of aortic aneurysms and early onset coronary and cerebrovascular disease. Based on arteriographic findings, a distinct cerebrovascular disease has been proposed for  ACTA2  heterozygous patients carrying the R179H mutation.Results   We present the first integrated analysis of a severely compromised patient with the R179H mutation and define the arterial pathology of  ACTA2 -related cerebrovascular disease. Histologically, striking morphological abnormalities were present in cerebral arteries of all sizes. Massive intimal smooth muscle cell proliferation, fragmentation of the elastic laminae and medial fibromuscular proliferation characterized large arteries whereas prominent vessel wall thickening, fibrosis and smooth muscle cell proliferation were unique changes in small arteries. The medial fibrosis and smooth muscle cell proliferation explain the characteristic radiologic appearance of “straight arteries” and suggest impaired function of mutant smooth muscle cells. Actin three-dimensional molecular modeling revealed critical positioning of R179 at the interface between the two strands of filamentous actin and destabilization of inter-strand bundling by the R179H mutation, explaining the severe associated phenotype.Conclusions  In conclusion, these characteristic clinical and pathologic findings confirm  ACTA2 -related cerebrovascular disease as a new cerebrovascular disorder for which new therapeutic strategies need to be designed.    Electronic supplementary material  The online version of this article (doi:10.1186/s40478-015-0262-7) contains supplementary material, which is available to authorized users.

The defining pathology of the new clinical and histopathologic entity ACTA2-related cerebrovascular disease