Atorvastatin Prevents Early Lipotoxic Remodelling in Right Ventricular Pacing-Induced Cardiomyopathy.

Authors

Yu-Sheng Lin, Wan-Chun Ho, Meng-Hung Lin, Ting-Yu Kuo, Chang-Min Chung, Pei-Chun Yen, Yung-Lung Chen, Huang-Chung Chen, Mien-Cheng Chen, Tzu-Hsien Tsai, Wei-Chieh Lee

Published in

CJC open. Volume 8. Issue 10. Pages 1298-1309. Epub Jul 30, 2026.

Abstract

Right ventricular (RV) pacing can induce metabolic and structural alterations in left ventricular (LV) myocardium, including lipid accumulation, glycogen depletion, and increased endoplasmic reticulum (ER) stress. This study evaluated protective effects of atorvastatin on RV pacing-induced metabolic dysfunction.
Fifteen male Lanyu miniature pigs were randomized into sham control (n = 5), RV pacing (n = 5), and RV pacing with atorvastatin treatment (n = 5) groups. RV pacing was achieved via ventricular lead implantation at the RV outflow tract, followed by complete atrioventricular block, with ventricular pacing maintained for at least 80 beats/min in dual-chamber, dual-sensing, dual-response, rate-responsive mode to provide atrial-synchronous ventricular pacing while allowing atrial sensing or pacing. The RV pacing with atorvastatin treatment group received atorvastatin (40 mg/d) starting 2 weeks before surgery until euthanasia at 6 months. Metabolic, histologic, and molecular parameters were assessed in LV myocardial tissue.
Compared with sham controls, RV pacing significantly increased myocardial lipid accumulation, with higher triglyceride (2.43 ± 0.17 vs 1.74 ± 0.14 μg/mg, P < 0.01) and diacylglycerol (2902 ± 567.7 vs 977.5 ± 182.5 μg/mg, P < 0.01) levels, and significantly reduced glycogen content (0.09 ± 0.03 vs 0.21 ± 0.03 μg/mg, P < 0.05). ER stress markers binding immunoglobulin protein and cleaved caspase-9 were markedly increased in the RV pacing group (P < 0.0001). Atorvastatin significantly reduced lipid accumulation (triglycerides: 1.83 ± 0.08 μg/mg; P < 0.05), ER stress, and apoptosis, but did not significantly restore glycogen levels.
RV pacing induces lipid accumulation, glycogen loss, and increased ER stress in the LV myocardium. Atorvastatin partially mitigated these effects by normalizing fatty acid metabolism and reducing ER stress and apoptosis, suggesting a potential role in attenuating early/subclinical RV pacing-induced metabolic remodelling.

PMID:
42861281
Bibliographic data and abstract were imported from PubMed on 12 Oct 2026.

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