期刊
JOURNAL OF CLINICAL MEDICINE
卷 11, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/jcm11061595
关键词
caveolin-3; arrhythmias; ion channels; intercellular communication; metabolic perturbation
资金
- National Natural Science Foundation of China [82070383]
Caveolin-3 plays a critical role in the cardiovascular system and is associated with cardiovascular diseases. Mutations in caveolin-3 can cause clinical phenotypic variations, including cardiomyopathy. These mutations affect current density and promote arrhythmia. Caveolin-3 overexpression or knockdown can contribute to the occurrence and development of arrhythmia. Additionally, caveolin-3 is related to obesity and glucose homeostasis.
Caveolin-3 is a muscle-specific protein on the membrane of myocytes correlated with a variety of cardiovascular diseases. It is now clear that the caveolin-3 plays a critical role in the cardiovascular system and a significant role in cardiac protective signaling. Mutations in the gene encoding caveolin-3 cause a broad spectrum of clinical phenotypes, ranging from persistent elevations in the serum levels of creatine kinase in asymptomatic humans to cardiomyopathy. The influence of Caveolin-3(CAV-3) mutations on current density parallels the effect on channel trafficking. For example, mutations in the CAV-3 gene promote ventricular arrhythmogenesis in long QT syndrome 9 by a combined decrease in the loss of the inward rectifier current (I-K1) and gain of the late sodium current (INa-L). The functional significance of the caveolin-3 has proved that caveolin-3 overexpression or knockdown contributes to the occurrence and development of arrhythmias. Caveolin-3 overexpression could lead to reduced diastolic spontaneous Ca2+ waves, thus leading to the abnormal L-Type calcium channel current-induced ventricular arrhythmias. Moreover, CAV-3 knockdown resulted in a shift to more negative values in the hyperpolarization-activated cyclic nucleotide channel 4 current (I-HCN4) activation curve and a significant decrease in I-HCN4 whole-cell current density. Recent evidence indicates that caveolin-3 plays a significant role in adipose tissue and is related to obesity development. The role of caveolin-3 in glucose homeostasis has attracted increasing attention. This review highlights the underlining mechanisms of caveolin-3 in arrhythmia. Progress in this field may contribute to novel therapeutic approaches for patients prone to developing arrhythmia.
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