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  • ACOX3 Dysfunction as a Potential Cause of Recurrent Spontaneous Vasospasm of Internal Carotid Artery.

ACOX3 Dysfunction as a Potential Cause of Recurrent Spontaneous Vasospasm of Internal Carotid Artery.

Translational stroke research (2020-01-25)
Joon-Tae Kim, So Yeon Won, KyungWook Kang, Sang-Hoon Kim, Man-Seok Park, Kang-Ho Choi, Tai-Seung Nam, Simone W Denis, Sacha Ferdinandusse, Ji Eun Lee, Seok-Yong Choi, Myeong-Kyu Kim
ABSTRACT

Recurrent spontaneous vasospasm of the extracranial internal carotid artery (RSV-eICA) is a rarely recognized cause of ischemic stroke in young adults. However, its pathophysiology remains largely unknown. Through whole-exome sequencing of the ACOX3 gene of two dizygotic Korean twin brothers affected by RSV-eICA, we identified two compound heterozygous missense variants c.235 T > G (p.F79 V) and c.665G > A (p.G222E). In silico analysis indicated that both variants were classified as pathogenic. In vitro ACOX3 enzyme assay indicated practically no enzyme activity in both F79 V and G222E mutants. To determine the effect of the mutants on vasospasm, we used a collagen contraction assay on human aortic smooth muscle cells (HASMC). Carbachol, a cholinergic agonist, induces contraction of HASMC. Knockdown of ACOX3 in HASMC, using siRNA, significantly repressed HASMC contraction triggered by carbachol. The carbachol-induced HASMC contraction was restored by transfection with plasmids encoding siRNA-resistant wild-type ACOX3, but not by transfection with ACOX3 G222E or by co-transfection with ACOX3 F79 V and ACOX3 G222E, indicating that the two ACOX3 mutants suppress carbachol-induced HASMC contraction. We propose that an ACOX3 dysfunction elicits a prolonged loss of the basal aortic myogenic tone. As a result, smooth muscles of the ICA's intermediate segment, in which the sympathetic innervation is especially rich, becomes hypersensitive to sympathomimetic stimuli (e.g., heavy exercise) leading to a recurrent vasospasm. Therefore, ACOX3 dysfunction would be a causal mechanism of RSV-eICA. For the first time, we report the possible involvement of ACOX3 in maintaining the basal myogenic tone of human arterial smooth muscle.

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Sigma-Aldrich
Anti-ACOX3 antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution
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Sigma-Aldrich
MISSION® esiRNA, targeting human ACOX3
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SKUPack SizeAvailabilityPriceQuantity
1 ea
1 Estimated to ship on February 23, 2025
$6,940.00