Caveolin-3 and Arrhythmias: Insights into the Molecular Mechanisms

He, Miaomiao; Qiu, Jie; Wang, Yan; Bai, Yang; Chen, Guangzhi

doi:10.3390/jcm11061595

Cited by 5 publications

(3 citation statements)

References 111 publications

(116 reference statements)

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“… 42 In addition, overexpression as well as downregulation of caveolin-3 (CAV3), a major regulator of T-tubule function, has been shown to be associated with the development of cardiac arrhythmias. 43 Moreover, the knockdown of junctophilin-2 (JPH2), which is abundant in the T-tubules has been described as interacting with the Ca 2+ -handling machinery via the RYR2 by provoking Ca 2+ -leak from the sarcoplasmic reticulum and inducing increased automaticity and arrhythmogenesis. 44 Consistent with these observations, in our model of right-sided atrial remodelling, we discovered that JPH2 was significantly decreased in RA from RHD rats compared to sham ( Figure 10 ).…”

Section: Discussionmentioning

confidence: 99%

Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease

Le Quilliec,

LeBlanc,

Neuilly

et al. 2024

Europace

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Context Right heart disease (RHD), characterized by right ventricular (RV) and atrial (RA) hypertrophy, and cardiomyocytes’ (CM) dysfunctions have been described to be associated with the incidence of atrial fibrillation (AF). RHD and AF have in common, an inflammatory status, but the mechanisms relating RHD, inflammation, and AF remain unclear. Hypotheses RHD generates electrophysiological and morphological remodelling affecting the CM, leading to atrial inflammation and increased AF susceptibility. Methods Pulmonary artery banding (PAB) was surgically performed (except for sham) on male Wistar rats (225-275g) to provoke an RHD. Twenty-one days (D21) post-surgery, all rats underwent echocardiography and electrophysiological studies (EPS). Optical mapping was performed in situ, on Langendorff-perfused hearts. The contractility of freshly isolated CM was evaluated and recorded during 1 Hz pacing in vitro. Histological analyses were performed on formalin-fixed RA to assess myocardial fibrosis, Connexin-43 (Cx43) levels, and CM morphology. RA levels of selected genes and proteins were obtained by qPCR and Western-blot respectively. Results PAB induced severe RHD identified by RV and RA hypertrophy. PAB rats were significantly more susceptible to AF than sham. Compared to sham RA CM from PAB rats were significantly elongated, and hypercontractile. RA CM from PAB animals showed significant augmentation of mRNA and protein levels of proinflammatory interleukin (IL)-6 and IL1β. Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) and junctophilin-2 (JPH2) were decreased in RA CM from PAB compared to sham rats. Conclusions RHD-induced arrhythmogenicity may occur due to dysfunctional SERCA2a and inflammatory signalling generated from injured RA CM, which leads to an increased risk of AF.

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Section: Discussionmentioning

confidence: 99%

Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease

Le Quilliec,

LeBlanc,

Neuilly

et al. 2024

Europace

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“…The Cav-3-encoding gene is located on human chromosome 3 p25, and its distribution is more limited than that of Cav-1 and Cav-2. Cav-3 is mainly expressed in vascular smooth muscle, myocardium and skeletal muscle ( He et al, 2022 ), as well as myoepithelial cells and glial cells in the mammary gland. Mutations in the Cav-3 coding region P140L can weaken p38, AKT and endoplasmic reticulum stress signals ( Stoppani et al, 2011 ).…”

Section: Relationship Between Caveolins and Breast Cancermentioning

confidence: 99%

Role of Caveolae family-related proteins in the development of breast cancer

Han,

Qiu,

et al. 2023

Front. Mol. Biosci.

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Breast cancer has become the most significant malignant tumor threatening women’s lives. Caveolae are concave pits formed by invagination of the plasma membrane that participate in many biological functions of the cell membrane, such as endocytosis, cell membrane assembly, and signal transduction. In recent years, Caveolae family-related proteins have been found to be closely related to the occurrence and development of breast cancer. The proteins associated with the Caveolae family-related include Caveolin (Cav) and Cavins. The Cav proteins include Cav-1, Cav-2 and Cav-3, among which Cav-1 has attracted the most attention as a tumor suppressor and promoting factor affecting the proliferation, apoptosis, migration, invasion and metastasis of breast cancer cells. Cav-2 also has dual functions of inhibiting and promoting cancer and can be expressed in combination with Cav-1 or play a regulatory role alone. Cav-3 has been less studied in breast cancer, and the loss of its expression can form an antitumor microenvironment. Cavins include Cavin-1, Cavin-2, Cavin-3 and Cavin-4. Cavin-1 inhibits Cav-1-induced cell membrane tubule formation, and its specific role in breast cancer remains controversial. Cavin-2 acts as a breast cancer suppressor, inhibiting breast cancer progression by blocking the transforming growth factor (TGF-β) signaling pathway. Cavin-3 plays an anticancer role in breast cancer, but its specific mechanism of action is still unclear. The relationship between Cavin-4 and breast cancer is unclear. In this paper, the role of Caveolae family-related proteins in the occurrence and development of breast cancer and their related mechanisms are discussed in detail to provide evidence supporting the further study of Caveolae family-related proteins as potential targets for the diagnosis and treatment of breast cancer.

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“…Caveolin-3 is a structural and regulatory protein that modulates the function of ion channels, including those involved in pace-making ( 141 ). Mutations in the gene encoding caveolin-3 have been linked to several cardiac diseases such as long QT syndrome, myocardial hypertrophy, and diabetic cardiomyopathy ( 142 , 143 ).…”

Section: San Remodeling and Dysfunction In Diabetesmentioning

confidence: 99%

Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives

Kury

Chacar²,

Alefishat³

et al. 2022

Front. Endocrinol.

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The sinoatrial node (SAN) is composed of highly specialized cells that mandate the spontaneous beating of the heart through self-generation of an action potential (AP). Despite this automaticity, the SAN is under the modulation of the autonomic nervous system (ANS). In diabetes mellitus (DM), heart rate variability (HRV) manifests as a hallmark of diabetic cardiomyopathy. This is paralleled by an impaired regulation of the ANS, and by a pathological remodeling of the pacemaker structure and function. The direct effect of diabetes on the molecular signatures underscoring this pathology remains ill-defined. The recent focus on the electrical currents of the SAN in diabetes revealed a repressed firing rate of the AP and an elongation of its tracing, along with conduction abnormalities and contractile failure. These changes are blamed on the decreased expression of ion transporters and cell-cell communication ports at the SAN (i.e., HCN4, calcium and potassium channels, connexins 40, 45, and 46) which further promotes arrhythmias. Molecular analysis crystallized the RGS4 (regulator of potassium currents), mitochondrial thioredoxin-2 (reactive oxygen species; ROS scavenger), and the calcium-dependent calmodulin kinase II (CaMKII) as metabolic culprits of relaying the pathological remodeling of the SAN cells (SANCs) structure and function. A special attention is given to the oxidation of CaMKII and the generation of ROS that induce cell damage and apoptosis of diabetic SANCs. Consequently, the diabetic SAN contains a reduced number of cells with significant infiltration of fibrotic tissues that further delay the conduction of the AP between the SANCs. Failure of a genuine generation of AP and conduction of their derivative waves to the neighboring atrial myocardium may also occur as a result of the anti-diabetic regiment (both acute and/or chronic treatments). All together, these changes pose a challenge in the field of cardiology and call for further investigations to understand the etiology of the structural/functional remodeling of the SANCs in diabetes. Such an understanding may lead to more adequate therapies that can optimize glycemic control and improve health-related outcomes in patients with diabetes.

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Caveolin-3 and Arrhythmias: Insights into the Molecular Mechanisms

Cited by 5 publications

References 111 publications

Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease

Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease

Role of Caveolae family-related proteins in the development of breast cancer

Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives

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