Altered Esophageal Smooth Muscle Phenotype in Achalasia.

Area of Science:

• Gastroenterology
• Esophageal Pathophysiology
• Smooth Muscle Biology

Background:

• Achalasia is characterized by impaired esophageal motility due to loss of inhibitory innervation.
• Associated changes in esophageal smooth muscle contractility and structure remain incompletely understood.

Purpose of the Study:

• To investigate the contractile phenotype, innervation, and inflammatory status of esophageal circular smooth muscle in achalasia patients.
• To correlate these findings with patient-specific parameters.

Main Methods:

• Circular smooth muscle biopsies from 25 achalasia patients undergoing peroral endoscopic myotomy.
• Immunocytochemistry and quantitative Polymerase Chain Reaction (qPCR) for analyzing innervation, neurotransmitters, smooth muscle proliferation, cellular phenotype, and collagen expression.
• Comparison with control tissue from esophagectomy and correlation with clinical factors.

Main Results:

• Increased mast cell number and collagen deposition observed in achalasia smooth muscle.
• Significantly reduced axon density compared to controls, irrespective of achalasia subtype.
• Altered smooth muscle phenotype with increased α-smooth muscle actin and smoothelin mRNA, alongside decreased myosin heavy chain and collagen 3a1 mRNA.

Conclusions:

• The thickened circular smooth muscle layer in achalasia is substantially denervated.
• Achalasia is associated with an altered smooth muscle contractile phenotype and fibrosis.
• Peroral endoscopic myotomy provides valuable tissue for studying achalasia pathophysiology.