Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10737-10742. doi: 10.1073/pnas.1706394114. Epub 2017 Sep 18.

Critical role of caveolin-1 in ocular neovascularization and multitargeted antiangiogenic effects of cavtratin via JNK.

Author information

1
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, People's Republic of China.
2
Center for Medical and Pharmaceutical Research, Binzhou Medical University, Yantai, Shandong 264003, People's Republic of China.
3
Laboratory of Molecular Genetics, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20824.
4
Department of Cell Biology, Weifang Medical University, Weifang 261053, People's Republic of China.
5
Medical Imaging Institute, Shandong Province Characteristical Key Subject, Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai 264003, People's Republic of China.
6
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, Sweden.
7
Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, United Kingdom.
8
National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, University of Leicester, Leicester LE3 9QP, United Kingdom.
9
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520; william.sessa@yale.edu rongju06512@gmail.com yzliu62@yahoo.com lixr6@mail.sysu.edu.cn.
10
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520.
11
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, People's Republic of China; william.sessa@yale.edu rongju06512@gmail.com yzliu62@yahoo.com lixr6@mail.sysu.edu.cn.

Abstract

Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization. Importantly, combined administration of cavtratin and anti-VEGF-A inhibited neovascularization more effectively than monotherapy, suggesting the existence of other pathways inhibited by cavtratin in addition to VEGF-A. Indeed, we found that cavtratin suppressed multiple critical components of pathological angiogenesis, including inflammation, permeability, PDGF-B and endothelial nitric oxide synthase expression (eNOS). Mechanistically, we show that cavtratin inhibits CNV and the survival and migration of microglia and macrophages via JNK. Together, our data demonstrate the unique advantages of cavtratin in antiangiogenic therapy to treat neovascular diseases.

KEYWORDS:

angiogenesis; caveolin-1; cavtratin; inflammation; ocular neovascularization

PMID:
28923916
PMCID:
PMC5635880
DOI:
10.1073/pnas.1706394114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center