From diverticulosis to complicated diverticular disease: Progression of myogenic alterations and oxidative imbalance.

Autor: Pallotta L; Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy., Pisano A; Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy., Vona R; Center for Gender-Specific Medicine, Italian National Institute of Health, Rome, Italy., Cappelletti M; Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy., Pignataro MG; Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy., Tattoli I; Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy., Maselli MA; Experimental Pharmacology Laboratory, National Institute of Gastroenterology 'S. de Bellis', Research Hospital, Castellana Grotte, Bari, Italy., Tarallo M; Department of Surgical Science, Sapienza University of Rome, Rome, Italy., Casella G; Department of Surgical Science, Sapienza University of Rome, Rome, Italy., Caronna R; Department of Surgical Science, Sapienza University of Rome, Rome, Italy., Tancredi A; Department of Methods and Models for Economy, Territory and Finance, Sapienza University of Rome, Rome, Italy., Scotti GB; Department of Surgical Science, Sapienza University of Rome, Rome, Italy., Scalese G; Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy., Matarrese P; Center for Gender-Specific Medicine, Italian National Institute of Health, Rome, Italy., Giordano C; Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy., Severi C; Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Jazyk: angličtina
Zdroj: Neurogastroenterology and motility [Neurogastroenterol Motil] 2024 Aug; Vol. 36 (8), pp. e14850. Date of Electronic Publication: 2024 Jun 24.
DOI: 10.1111/nmo.14850
Abstrakt: Background: The natural history and pathophysiology of diverticular disease (DD) are still uncertain. An ex-vivo human complicated DD (cDD) model has recently shown a predominant transmural oxidative imbalance. The present study aims to evaluate whether the previously described alterations may precede the symptomatic form of the disease.
Methods: Colonic surgical samples obtained from patients with asymptomatic diverticulosis (DIV), complicated DD, and controls were systematically and detailed morphologically and molecularly analyzed. Therefore, histologic, histomorphometric, immunohistochemical evaluation, and gene and protein expression analysis were performed to characterize colonic muscle changes and evaluate chronic inflammation, oxidative imbalance, and hypoxia. Functional muscle activity was tested on strips and isolated cells in response to contractile and relaxant agents.
Key Results: Compared with controls, DD showed a marketed increase in muscle layer thickness, smooth muscle cell syncytium disarray, and increased interstitial fibrosis; moreover, the observed features were more evident in the cDD group. These changes mainly affected longitudinal muscle and were associated with altered contraction-relaxation dynamics and fibrogenic switch of smooth muscle cells. Chronic lymphoplasmacytic inflammation was primarily evident in the mucosa and spared the muscle. A transmural increase in carbonylated and nitrated proteins, with loss of antioxidant molecules, characterized both stages of DD, suggesting early oxidative stress probably triggered by recurrent ischemic events, more pronounced in cDD, where HIF-1 was detected in both muscle and mucosa.
Conclusion & Inferences: The different DD clinical scenarios are part of a progressive process, with oxidative imbalance representing a new target in the management of DD.
(© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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