Endothelium-specific overexpression of human IC53 downregulates endothelial nitric oxide synthase activity and elevates systolic blood pressure in mice
| Autor: | Ruifeng Yang, Hongliang Li, Yu-Sheng Wei, Hua Cai, Hou-Zao Chen, Li-Hong Sun, Tie-Min Ma, De-Pei Liu, Yue Huang, Xiang Lv, Ran Zhang, Chih-Chuan Liang, Ming-Lei Zhuo, Jing-Zhou Chen, Ru-Tai Hui, Guang Liu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Physiology
Vasodilator Agents Blood Pressure Cell Cycle Proteins Vasodilation Umbilical vein Mice chemistry.chemical_compound Enos Cloning Molecular Promoter Regions Genetic Cells Cultured Regulation of gene expression Endothelin-1 biology Intracellular Signaling Peptides and Proteins Cadherins Nitric oxide synthase Phenotype medicine.anatomical_structure Hypertension RNA Interference Cardiology and Cardiovascular Medicine medicine.medical_specialty Genotype Nitric Oxide Synthase Type III Endothelium Systole Down-Regulation Mice Transgenic Nerve Tissue Proteins Nitric Oxide Gene Expression Regulation Enzymologic Nitric oxide Downregulation and upregulation Antigens CD Physiology (medical) Internal medicine medicine Animals Humans RNA Messenger Dose-Response Relationship Drug Tumor Suppressor Proteins Endothelial Cells Original Articles biology.organism_classification Mice Inbred C57BL Endocrinology chemistry biology.protein |
| Zdroj: | Cardiovascular Research. 84:292-299 |
| ISSN: | 0008-6363 |
| Popis: | Aims Hypertension is one of the major risk factors for cardiovascular diseases. Endothelial cells (ECs) exert important functions in the regulation of blood pressure. A novel gene, IC53 , as an isoform of the cyclin-dependent kinase (CDK)-binding protein gene C53 , is mainly expressed in vascular ECs and is upregulated in the failing heart of rats. Overexpression of IC53 promotes proliferation of ECs. To examine whether IC53 plays a role in the regulation of vascular tone and blood pressure, we constructed a transgenic (tg) mouse model of the IC53 gene and studied its phenotypes relevant to vascular function. Methods and results IC53 cDNA was cloned from a human aorta cDNA library. Using the endothelium-specific VE-cadherin promoter, we constructed tg mice in which IC53 was specifically overexpressed in vascular endothelia and found that the tg mice exhibit elevated systolic blood pressure (SBP) in contrast to the wild-type (wt) controls. Further studies revealed impaired endothelium-dependent vasodilation, reduced nitric oxide (NO) production and decreased endothelial NO synthase (eNOS) expression, and activity in the tg mice. Inhibition of IC53 in human umbilical vein ECs induces upregulation of eNOS activity. Conclusion Our results indicate that IC53 participates in the regulation of vascular homeostasis. Endothelium-specific overexpression of IC53 is associated with elevated SBP, which may be in part attributed to the downregulation of eNOS signalling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|