Altered Esophageal Smooth Muscle Phenotype in Achalasia
Background/Aims: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Journal of neurogastroenterology and motility - 30(2024), 2 vom: 30. Apr., Seite 166-176 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rodrigues, David M [VerfasserIn] |
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| Links: |
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| Themen: |
Collagen |
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| Anmerkungen: |
Date Revised 10.04.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.5056/jnm23024 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360278515 |
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| 245 | 1 | 0 | |a Altered Esophageal Smooth Muscle Phenotype in Achalasia |
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| 500 | |a Date Revised 10.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Background/Aims: 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 | ||
| 520 | |a Methods: 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 | ||
| 520 | |a Results: 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 | ||
| 520 | |a Conclusions: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Collagen | |
| 650 | 4 | |a Fibrosis | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Innervation | |
| 650 | 4 | |a Smooth muscle | |
| 700 | 1 | |a Lourenssen, Sandra R |e verfasserin |4 aut | |
| 700 | 1 | |a Kataria, Jay |e verfasserin |4 aut | |
| 700 | 1 | |a Paterson, William G |e verfasserin |4 aut | |
| 700 | 1 | |a Blennerhassett, Michael G |e verfasserin |4 aut | |
| 700 | 1 | |a Bechara, Robert |e verfasserin |4 aut | |
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