J Neurogastroenterol Motil  https://doi.org/10.5056/jnm23024
Altered Esophageal Smooth Muscle Phenotype in Achalasia
David M Rodrigues,2 Sandra R Lourenssen,1 Jay Kataria,1 William G Paterson,1,2 Michael G Blennerhassett,1,2 and Robert Bechara1,2*
1Gastrointestinal Diseases Research Unit, Kingston General Hospital, Kingston, ON, Canada; and 2Division of Gastroenterology, Queen’s School of Medicine, Hotel Dieu Hospital, Kingston, ON, Canada
Correspondence to: Robert Bechara, MD
Division of Gastroenterology, Department of Medicine, Queen’s University, 76 Stuart Street Kingston, ON K7L 2V7, Canada
Tel: +1-613-544-3310, Fax: +1-613-544-3400, E-mail: robert.bechara@kingstonhsc.ca
Received: February 5, 2023; Revised: April 12, 2023; Accepted: May 11, 2023; Published online: August 2, 2023
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

Achalasia is a disorder characterized by impairment in lower esophageal sphincter relaxation and esophageal aperistalsis, caused primarily by loss of inhibitory innervation. However, little is known about associated changes in esophageal smooth muscle. We examined the contractile phenotype and innervation of the circular smooth muscle, as well as inflammatory status, and correlated these with patient-specific parameters.
Circular smooth muscle biopsies were obtained in consecutive patients with achalasia undergoing peroral endoscopic myotomy. Axonal innervation and neurotransmitter subtypes were determined with immunocytochemistry, and this was used with quantitative Polymerase Chain Reaction (qPCR) to characterize smooth muscle proliferation and cellular phenotype, as well as collagen expression. These were compared to control tissue obtained at esophagectomy and correlated with patient demographic factors including age, onset of symptoms, and Eckhardt score.
Biopsies of smooth muscle were obtained from 25 patients with achalasia. Overall, there was increased mast cell number and collagen deposition but increased smooth muscle cell proliferation vs control. There was a striking drop in axon density over controls, with no differences among subtypes of achalasia. Immunocytochemical analysis showed increased expression of the contractile marker α-smooth muscle actin, principally in Type 1 achalasia, that increased with disease duration, while qPCR identified increased mRNA for smoothelin with decreased myosin heavy chain and collagen 3a1, but not collagen 1a1.
The thickened circular smooth muscle layer in achalasia is largely denervated, with an altered contractile phenotype and fibrosis. Biopsies obtained during peroral endoscopic myotomy provide a means to further study the pathophysiology of achalasia.
Keywords: Collagen; Fibrosis; Inflammation; Innervation; Smooth muscle

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