Key result
Perindopril prevents angiotensin II-induced loss of t-tubular integrity and altered Ca2+ handling in colitis mice.
Why the study?
Extraintestinal manifestations of inflammatory bowel disease include attenuated ventricular contractile function and arrhythmia, but the mechanisms of these changes remain unclear.
Does perindopril prevent ventricular excitation-contraction coupling attenuation in a mouse model of colitis?
Does perindopril prevent ventricular excitation-contraction coupling attenuation in a mouse model of colitis?
Suppression of AngII signaling with perindopril prevents t-tubular remodeling and altered calcium handling in a murine colitis model, highlighting a potential treatment for cardiac manifestations of IBD.
Should not yet change practice for IBD cardiac manifestations; leaves open full excitation-contraction coupling restoration by ACE inhibition.
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.
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V et al. (2026) studied Inflammatory bowel disease (IBD) with cardiac manifestations. Perindopril was evaluated on Changes in cardiac function (cell shortening, [Ca2+]i, ROS, and t-tubular density). In a mouse model of colitis, ACE inhibition with perindopril prevented the angiotensin II-induced loss of t-tubular integrity, ROS production, autophagy, and altered cellular Ca2+ handling.
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