ArticleFrontiers in cardiovascular medicine2026
Titin modulation and left ventricular remodelling in chronic primary mitral regurgitation.
Article in Frontiers in cardiovascular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Background: Left ventricular (LV) remodelling in mitral valve prolapse (MVP) is usually induced by chronic mitral regurgitation (MR), however it can also be disproportionate to the volume load, generating the hypothesis of MVP cardiomyopathy. Changes in the sarcomeric protein titin could contribute to its underlying pathophysiology. Objectives: To investigate the role of titin modulation as a mechanism of disproportionate LV remodelling in MVP patients. Methods: Myocardial biopsies from 16 patients with MVP and severe MR were compared with 6 controls. All patients underwent pre-operative transthoracic echocardiography and cardiac magnetic resonance imaging. Titin modifications were analyzed by gel electrophoresis and western blotting. Results: Five patients had disproportionate LV remodelling. Compared to controls, the larger N2BA isoform was significantly upregulated in MVP patients, displaying a significantly higher N2BA/N2B isoform ratio (0.589 ± 0.055 vs. 0.479 ± 0.024, Conclusions: MVP patients with severe MR demonstrate significant changes in titin isoform ratio, phosphorylation, oxidation and ubiquitination compared to controls. Disproportionate LV remodelling was correlated with increased phosphorylation and showed a trend towards increased N2BA titin, both markers of decreased myocardial stiffness.
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