1. Academic Validation
  2. FGF13 deficiency ameliorates calcium signaling abnormality in heart failure by regulating microtubule stability

FGF13 deficiency ameliorates calcium signaling abnormality in heart failure by regulating microtubule stability

  • Biochem Pharmacol. 2024 Jul:225:116329. doi: 10.1016/j.bcp.2024.116329.
Ran Zhao 1 Yingke Yan 1 Yiming Dong 1 Xiangchong Wang 2 Xuyan Li 3 Ruoyang Qiao 3 Huaxing Zhang 4 Nanqi Cui 5 Yanxue Han 1 Cong Wang 1 Jiabing Han 1 Qianli Ma 6 Demin Liu 7 Jing Yang 8 Guoqiang Gu 9 Chuan Wang 10
Affiliations

Affiliations

  • 1 Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China.
  • 2 Department of Pharmacology, Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Hebei University of Chinese Medicine, Shijiazhuang 050091, China.
  • 3 College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
  • 4 Core Facilities and Centers, Hebei Medical University, Shijiazhuang 050017, China.
  • 5 Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
  • 6 Department of Cardiac Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
  • 7 Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
  • 8 Department of Pathology and Pathophysiology, Hangzhou Normal University, Hangzhou 311121, China. Electronic address: 20220059@hznu.edu.cn.
  • 9 Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China. Electronic address: guguoqiang@hebmu.edu.cn.
  • 10 Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, The Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: wangchuan@hebmu.edu.cn.
Abstract

Calcium signaling abnormality in cardiomyocytes, as a key mechanism, is closely associated with developing heart failure. Fibroblast Growth Factor 13 (FGF13) demonstrates important regulatory roles in the heart, but its association with cardiac calcium signaling in heart failure remains unknown. This study aimed to investigate the role and mechanism of FGF13 on calcium mishandling in heart failure. Mice underwent transaortic constriction to establish a heart failure model, which showed decreased ejection fraction, fractional shortening, and contractility. FGF13 deficiency alleviated cardiac dysfunction. Heart failure reduces calcium transients in cardiomyocytes, which were alleviated by FGF13 deficiency. Meanwhile, FGF13 deficiency restored decreased Cav1.2 and Serca2α expression and activity in heart failure. Furthermore, FGF13 interacted with microtubules in the heart, and FGF13 deficiency inhibited the increase of microtubule stability during heart failure. Finally, in isoproterenol-stimulated FGF13 knockdown neonatal rat ventricular myocytes (NRVMs), wildtype FGF13 overexpression, but not FGF13 mutant, which lost the binding site of microtubules, promoted calcium transient abnormality aggravation and Cav1.2 downregulation compared with FGF13 knockdown group. Generally, FGF13 deficiency improves abnormal calcium signaling by inhibiting the increased microtubule stability in heart failure, indicating the important role of FGF13 in cardiac calcium homeostasis and providing new avenues for heart failure prevention and treatment.

Keywords

Calcium signalling; Calcium transients; Fibroblast growth factor 13; Heart failure; L-type calcium channel; Microtubules.

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