scholarly journals Characteristic Cerebrovascular Findings Associated with ACTA2 Gene Mutations

2019 ◽  
Vol 46 (3) ◽  
pp. 342-343 ◽  
Author(s):  
Andrew Zhang ◽  
Alexandria Jo ◽  
Karen Grajewski ◽  
John Kim
Keyword(s):  
Smooth Muscle ◽  
Ischemic Stroke ◽  
Aortic Aneurysm ◽  
Early Onset ◽  
Thoracic Aortic Aneurysm ◽  
Gene Mutations ◽  
Muscle Dysfunction ◽  
Imaging Appearance ◽  
Cerebrovascular Imaging ◽  
Smooth Muscle Dysfunction

A specific mutation (Arg179) of the ACTA2 gene has previously been described to cause a syndrome of multisystemic smooth muscle dysfunction with an extremely characteristic cerebrovascular appearance.1 Accurate neuroimaging diagnosis of this entity is important as this syndrome predisposes to complications such as early-onset ischemic stroke and ascending thoracic aortic aneurysm.2,3 The following case demonstrates a previously undescribed ACTA2 mutation (Met46) with an identical cerebrovascular imaging appearance to that of Arg179 mutations, but a less severe overall phenotype.

scholarly journals An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Christian L. Lino Cardenas ◽  
Chase W. Kessinger ◽  
Yisha Cheng ◽  
Carolyn MacDonald ◽  
Thomas MacGillivray ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Aortic Aneurysm ◽  
Thoracic Aortic Aneurysm ◽  
Muscle Dysfunction ◽  
Smooth Muscle Dysfunction

Abstract 219: Early-onset Cerebrovascular Disease and Smooth Muscle Dysfunction Associated with a Novel Mylk1 Mutation

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Matheus Malta de Sá ◽  
Heather J Fullerton ◽  
Kevin A Shapiro
Keyword(s):  
Smooth Muscle ◽  
Cerebrovascular Disease ◽  
Early Onset ◽  
Novel Mutation ◽  
Muscle Dysfunction ◽  
Atp Binding ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Atp Binding Site ◽  
Smooth Muscle Dysfunction

Introduction: Genetic arteriopathies are an important cause of early-onset cerebrovascular disease. We report a novel mutation in the gene for myosin light chain kinase 1 ( Mylk1 ), a protein essential for smooth muscle contractility, leading to vascular smooth muscle dysfunction and stroke. Our patient presented with signs of systemic smooth muscle dysfunction at birth, and developed left hemiparesis due to right MCA stroke at 8 months of age. Cerebral angiogram showed tortuous intracranial vessels with right M1 occlusion and extensive proliferative ICA collaterals. Methods: Whole exome sequencing showed a de novo mutation in Mylk1 leading to a P1588L substitution in the ATP binding site. To understand the effect of this substitution on protein function, we built a homology model of MYLK1 based on the resolved crystal structure of MYLK4. We then investigated conformational changes in the secondary structure using Molecular Dynamics Simulation. The protein was solvated in TIP3P water and simulated at 310K, at 1 bar, in 150 mmol/L of NaCl. The integrity of the model was verified by Ramachandran plot, with 99.6% of the amino acids in allowed regions. Results: The P1588L substitution alters the loop-helix structure of the ATP binding domain, which is integral for the catalytic activity of MYLK1. The substitution also affects the polarity and the flexibility of the ATP binding site, which is likely to affect the docking and binding of ATP. Conclusions: Using in silico modeling, we demonstrated that a novel mutation in Mylk1 alters protein structure, likely interfering with systemic and vascular smooth muscle contractility and resulting in a clinical phenotype of stroke in childhood.

scholarly journals Homeostatic and therapeutic roles of VIP in smooth muscle function: myo-neuroimmune interactions

2009 ◽  
Vol 297 (4) ◽  
pp. G716-G725 ◽  
Author(s):  
Xuan-Zheng Shi ◽  
Sushil K. Sarna
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Response ◽  
Muscle Function ◽  
Contractile Response ◽  
Enteric Neurons ◽  
Muscle Dysfunction ◽  
Spontaneous Release ◽  
Circular Smooth Muscle ◽  
Smooth Muscle Function ◽  
Smooth Muscle Dysfunction

We tested the hypothesis that spontaneous release of vasoactive intestinal peptide (VIP) from enteric neurons maintains homeostasis in smooth muscle function in mild inflammatory insults and that infusion of exogenous VIP has therapeutic effects on colonic smooth muscle dysfunction in inflammation. In vitro experiments were performed on human colonic circular smooth muscle tissues and in vivo on rats. The incubation of human colonic circular smooth muscle strips with TNF-α suppressed their contractile response to ACh and the expression of the pore-forming α1C subunit of Cav1.2 channels. VIP reversed both effects by blocking the translocation of NF-κB to the nucleus and its binding to the κB recognition sites on hα1C1b promoter. The translocation of NF-κB was inhibited by blocking the degradation of IκBβ. Induction of inflammation by a subthreshold dose of 17 mg/kg trinitrobenzene sulfonic acid (TNBS) in rats moderately decreased muscularis externa concentration of VIP, and it had little effect on the contractile response of circular smooth muscle strips to ACh. The blockade of VIP and pituitary adenylate cyclase-activating peptide receptors 1/2 during mild inflammatory insult significantly worsened the suppression of contractility and the inflammatory response. The induction of more severe inflammation by 68 mg/kg TNBS induced marked suppression of colonic circular muscle contractility and decrease in serum VIP. Exogenous infusion of VIP by an osmotic pump reversed these effects. We conclude that the spontaneous release of VIP from the enteric motor neurons maintains homeostasis in smooth muscle function in mild inflammation by blocking the activation of NF-κB. The infusion of exogenous VIP mitigates colonic inflammatory response and smooth muscle dysfunction.

scholarly journals Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis

1998 ◽  
Vol 32 (1) ◽  
pp. 123-127 ◽  
Author(s):  
Mark R Adams ◽  
Jacqui Robinson ◽  
Robyn McCredie ◽  
J.Paul Seale ◽  
Keld E Sorensen ◽  
...  
Keyword(s):  
At Risk ◽  
Smooth Muscle ◽  
Muscle Dysfunction ◽  
Smooth Muscle Dysfunction

scholarly journals High-resolution iris and retinal imaging in multisystemic smooth muscle dysfunction syndrome due to a novel Asn117Lys substitution in ACTA2: a case report

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Aisling B. Mc Glacken-Byrne ◽  
David Prentice ◽  
Danial Roshandel ◽  
Michael R. Brown ◽  
Philip Tuch ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Case Report ◽  
High Resolution ◽  
Retinal Imaging ◽  
Muscle Dysfunction ◽  
Smooth Muscle Dysfunction

MR Imaging Diagnosis of ACTA2

Neurographics ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 409-413
Author(s):  
R. Farias-Moeller ◽  
S.M. Lew ◽  
R. Sacho ◽  
T.G. Kelly
Keyword(s):  
Smooth Muscle ◽  
Clinical Manifestations ◽  
Muscle Dysfunction ◽  
Imaging Features ◽  
Imaging Diagnosis ◽  
Childhood Stroke ◽  
Intestinal Dysmotility ◽  
Prognostic Implications ◽  
Smooth Muscle Dysfunction ◽  
Large Vessel Disease

Smooth muscle alpha-2 actin (ACTA2) mutations are associated with diffuse smooth-muscle dysfunction syndrome and produce distinct imaging features. Clinical manifestations include intrathoracic large-vessel disease, nonreactive mydriasis, bladder hypotonia, and intestinal dysmotility. ACTA2 mutations are associated with childhood stroke due to diffuse cerebral arteriopathy distinct from moyamoya disease. Recognition of this syndrome has important clinical and prognostic implications. The purpose of this article is to review the unique imaging phenotypes associated with ACTA2 mutations, including vascular and nonvascular abnormalities.

scholarly journals Bladder smooth muscle dysfunction in patients with irritable bowel syndrome.

Gut ◽  
1986 ◽  
Vol 27 (9) ◽  
pp. 1014-1017 ◽  
Author(s):  
P J Whorwell ◽  
E W Lupton ◽  
D Erduran ◽  
K Wilson
Keyword(s):  
Irritable Bowel Syndrome ◽  
Smooth Muscle ◽  
Muscle Dysfunction ◽  
Bladder Smooth Muscle ◽  
Irritable Bowel ◽  
Smooth Muscle Dysfunction
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