October 1, 1999Circulation Research
Angiotensin II Stimulates Platelet-Derived Growth Factor-B Chain Expression in Newborn Rat Vascular Smooth Muscle Cells and Neointimal Cells Through Ras, Extracellular Signal–Regulated Protein Kinase, and c-Jun N-Terminal Protein Kinase Mechanisms
Key result
Angiotensin II stimulates PDGF-B gene expression in newborn rat VSMCs via Ras-ERK and JNK.
Population
Cultured newborn rat medial vascular smooth muscle cells (VSMCs), neointimal VSMCs, and adult rat VSMCs
Comparison
Angiotensin II (Ang II) exposure vs Adult rat VSMCs or untreated cells
Design
Preclinical
Authors
Discussion
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Member takes
Implication
No immediate clinical implications; leaves open whether these pathways drive human vascular proliferative disorders.
Key Points
- To identify the signaling pathways through which angiotensin II induces PDGF-B chain gene expression in newborn versus adult rat vascular smooth muscle cells.
- Cultured medial vascular smooth muscle cells from newborn and adult rats as well as neointimal cells, stimulating them with angiotensin II.
- Assessed mRNA levels, kinase activation (ERK, JNK, p38), and transcriptional activity using kinase inhibitors and transient transfection with dominant-negative Ras, ERK, JNK, and p38 constructs.
- Angiotensin II stimulated PDGF-B mRNA expression via the AT1 receptor in newborn and neointimal vascular smooth muscle cells, but not in adult cells.
- Dominant-negative forms of Ras, ERK, and JNK—as well as the MEK inhibitor PD98059—abrogated angiotensin II-induced PDGF-B promoter activation and mRNA synthesis, whereas p38 inhibition had no effect.
- Angiotensin II activated ERK and JNK in adult vascular smooth muscle cells but induced the transcription factor Egr-1 far more weakly than in newborn cells.
Structured PICO
P
Population
Cultured newborn rat medial vascular smooth muscle cells (VSMCs), neointimal VSMCs, and adult rat VSMCs
I
Intervention
Angiotensin II (Ang II) exposure
C
Comparator
Adult rat VSMCs or untreated cells
O
Outcome
PDGF-B chain mRNA expression and transcriptional activationsurrogate
Angiotensin II stimulates PDGF-B chain gene expression in newborn and neointimal vascular smooth muscle cells through Ras-ERK and JNK pathways, providing mechanistic insight into vascular proliferative disorders.
Cite This Study
Deguchi et al. (1999) studied Vascular proliferative disorders. Angiotensin II was evaluated on PDGF-B chain mRNA expression. Angiotensin II stimulates PDGF-B chain gene expression in newborn rat vascular smooth muscle cells through mechanisms involving Ras-ERK and JNK.