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Blood pressure regulates platelet-derived growth factor A-chain gene expression in vascular smooth muscle cells in vivo. An autocrine mechanism promoting hypertensive vascular hypertrophy
- Source :
- Journal of Clinical Investigation. 95:1140-1150
- Publication Year :
- 1995
- Publisher :
- American Society for Clinical Investigation, 1995.
-
Abstract
- To clarify the role of PDGF A-chain in hypertensive vascular hypertrophy of spontaneously hypertensive rats (SHRs), we studied levels of PDGF A-chain gene expression and transcription factors related to the gene in vascular smooth muscle cells (VSMCs) of SHRs in vivo. RNase protection assay and in situ hybridization showed that PDGF A-chain mRNA levels in VSMCs of SHRs were twofold higher than in those of normotensive Wistar-Kyoto rats. Gel retardation assays showed that levels of Sp1 and AP-2 in VSMCs of SHRs were twofold more abundant than in those of Wistar-Kyoto rats. Treatment with four pharmacologically different species of antihypertensive drugs for 2 wk decreased the levels of both PDGF A-chain mRNA and Sp1, but not AP-2 level in VSMCs of SHRs with regression of aortic hypertrophy, indicating that increases in levels of both PDGF A-chain mRNA and Sp1 in VSMCs of SHRs were associated with high blood pressure. These results suggest that high blood pressure is a stimulus which upregulates PDGF A-chain gene expression in VSMCs of SHRs, resulting in an autocrine enhancement in hypertensive vascular hypertrophy, and that the activation of the gene may be mediated through increases in Sp1 in these cells.
- Subjects :
- Male
medicine.medical_specialty
Platelet-derived growth factor
Vascular smooth muscle
Systole
Molecular Sequence Data
Blood Pressure
In situ hybridization
Biology
Polymerase Chain Reaction
Rats, Inbred WKY
Muscle, Smooth, Vascular
Muscle hypertrophy
Rats, Sprague-Dawley
chemistry.chemical_compound
Heart Rate
Rats, Inbred SHR
Internal medicine
Gene expression
medicine
Animals
RNA, Messenger
cardiovascular diseases
Autocrine signalling
Antihypertensive Agents
Aorta
In Situ Hybridization
Platelet-Derived Growth Factor
Regulation of gene expression
Base Sequence
Hypertrophy
General Medicine
Rats
Endocrinology
Gene Expression Regulation
chemistry
Hypertension
cardiovascular system
biology.protein
Tunica Media
Platelet-derived growth factor receptor
Transcription Factors
Research Article
Subjects
Details
- ISSN :
- 00219738
- Volume :
- 95
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....b73cd7de23e7ddeaff52b6605c557177
- Full Text :
- https://doi.org/10.1172/jci117762