Nuclear Smooth Muscle α-actin Participates in Vascular Smooth Muscle Cell Differentiation.

Missense variants throughout , encoding smooth muscle α-actin (αSMA), predispose to adult-onset thoracic aortic disease, but variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by diverse childhood-onset vascular diseases. Here we show that αSMA localizes to the nucleus in wildtype (WT) smooth muscle cells (SMCs), enriches in the nucleus with SMC differentiation, and associates with chromatin remodeling complexes and SMC contractile gene promotors. The p.

Augmenting Mitochondrial Respiration in Immature Smooth Muscle Cells with an Pathogenic Variant Mitigates Moyamoya-like Cerebrovascular Disease.

pathogenic variants altering arginine 179 cause childhood-onset strokes due to moyamoya disease (MMD)-like occlusion of the distal internal carotid arteries. A smooth muscle cell (SMC)-specific knock-in mouse model () inserted the mutation into 67% of aortic SMCs, whereas explanted SMCs were uniformly heterozygous. SMCs fail to fully differentiate and maintain stem cell-like features, including high glycolytic flux, and increasing oxidative respiration (OXPHOS) with nicotinamide riboside (NR) drives the mutant SMCs to differentiate and decreases migration.

Nuclear Smooth Muscle α-actin in Vascular Smooth Muscle Cell Differentiation.

Missense variants throughout , encoding smooth muscle α-actin (αSMA), predispose to adult onset thoracic aortic disease, but variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by childhood-onset diverse vascular diseases. Our data indicate that αSMA localizes to the nucleus in wildtype (WT) smooth muscle cells (SMCs), enriches in the nucleus with SMC differentiation, and associates with chromatin remodeling complexes and SMC contractile gene promotors, and the p.R179 variant decreases nuclear localization of αSMA.

Systematic mapping of the conformational landscape and dynamism of soluble fibrinogen.

Background: Fibrinogen is a soluble, multisubunit, and multidomain dimeric protein, which, upon its proteolytic cleavage by thrombin, is converted to insoluble fibrin, initiating polymerization that substantially contributes to clot growth. Fibrinogen contains numerous, transiently accessible "cryptic" epitopes for hemostatic and immunologic proteins, suggesting that fibrinogen exhibits conformational flexibility, which may play functional roles in its temporal and spatial interactions. Hitherto, there have been limited integrative approaches characterizing the solution structure and internal flexibility of fibrinogen.