Work

Active Colitis Attenuates Ventricular Excitation–Contraction Coupling by T-Tubular Remodeling

Year: 2026

Type: article

Abstract: In patients, extraintestinal manifestations of inflammatory bowel disease (IBD) are attenuated ventricular contractile function and arrhythmia. To determine the mechanism of IBD-induced changes in ventricular function, we used a mouse model of dextran sodium sulfate (3.5% weight/volume; 7 days)-induced colitis. Changes in cardiac function were quantified in isolated ventricular myocytes (VM) by cell shortening, imaging of [Ca2+]i, reactive oxygen species (ROS), and t-tubular density. During colitis, VMs exhibited attenuated cell-shortening and altered Ca2+-handling properties. A prolonged Ca2+ transient (CaT) rise time correlated with an increased coefficient of variation in the subcellular Ca2+ release and an attenuated t-tubular density. T-tubular loss was accompanied by increased ROS production, calpain-2 (CAPN2) expression, junctophilin-2 (JPH-2) cleavage, and autophagy. Inhibition of Angiotensin-converting enzyme during colitis (Perindopril: 3 mg/kg/day) prevented the increase in CAPN2, ROS production, autophagy, and t-tubular remodeling. It failed, however, to restore full length JPH-2. We conclude that, during IBD, the angiotensin II (AngII)-induced loss of t-tubular integrity and altered cellular Ca2+ handling can be prevented by suppression of the AngII-dependent increase in CAPN2 and autophagy and thus suppression of AngII signaling might benefit IBD patients with cardiac manifestations of the disease.

Source: Biomolecules

DOI: 10.3390/biom16040503

Authors: Edward J. Ouille V, Carlos H. Pereira, Ygor Marinho, Giedrius Kanaporis, Kathrin Banach

Institution: Rush University Medical Center

Language: English

Topic: Cardiac electrophysiology and arrhythmias

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258