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Published on: June 8, 2022
Inhibitory effect of caveolin-1 in vascular endothelial cells, pericytes and smooth muscle cells
Hongping Xu1, Liwei Zhang1, Wei Chen1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
Abstract:
Caveolin-1 (Cav1) is the principle structural protein of caveolae. It plays important roles in the vascular system under both physiological and pathological conditions. Although Cav1 has been shown to inhibit microvascular permeability and has been considered as a tumor-suppressor for years, the underlying cellular mechanism has yet to be discovered. Here, we systematically investigated Cav1 functions in the main types of vascular cells, including endothelial cells (ECs), pericytes (PCs) and smooth muscle cells (SMCs). We synthesized a cell-permeable peptide called cavtratin that is derived from the Cav1 scaffolding domain. We found that cavtratin inhibited ECs in all assays, including survival, proliferation, migration and permeability assays. It also inhibited the proliferation of PCs and SMCs but had no effect on their survival or migration. The inhibitory effect of cavtratin on the proliferation of all vascular cells suggests that Cav1 plays important roles in vascular development and angiogenesis. Under physiological condition, the main function of Cav1 is to inhibit EC permeability.
Insights
Caveolin-1 (Cav1) is crucial for vascular health, regulating cell functions and permeability. This study reveals Cav1
Area of Science:
- Vascular Biology
- Cellular Mechanisms
- Protein Function
Background:
- Caveolin-1 (Cav1) is the primary structural protein of caveolae.
- Cav1 is implicated in vascular system functions and disease.
- Its precise cellular mechanisms, particularly in vascular cells, remain unclear.
Purpose of the Study:
- To investigate Cav1 functions in endothelial cells (ECs), pericytes (PCs), and smooth muscle cells (SMCs).
- To elucidate the cellular mechanisms underlying Cav1's roles in the vascular system.
- To assess the impact of targeting the Cav1 scaffolding domain.
Main Methods:
- Systematic investigation of Cav1 functions across major vascular cell types.
- Synthesis of a cell-permeable peptide, cavtratin, derived from the Cav1 scaffolding domain.
- Assays evaluating cell survival, proliferation, migration, and permeability.
Main Results:
- Cavtratin inhibited EC survival, proliferation, migration, and permeability.
- Cavtratin inhibited PC and SMC proliferation but not their survival or migration.
- These findings suggest Cav1's significant role in vascular development and angiogenesis.
Conclusions:
- Cav1 plays critical roles in the proliferation and function of multiple vascular cell types.
- Cav1 is essential for inhibiting microvascular permeability under physiological conditions.
- Targeting Cav1 may offer therapeutic avenues for vascular development and disease.
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