What question did this study set out to answer?

To determine the molecular mechanisms by which tumor necrosis factor-alpha (TNF) stimulates migration and proliferation in vascular smooth muscle cells, specifically in relation to platelet-derived growth factor (PDGF) signaling.

December 15, 2004Cardiovascular Research

Activation of vascular smooth muscle cells by TNF and PDGF: overlapping and complementary signal transduction mechanisms

Q: What is the clinical evidence from this study?

Study design: Other. Population: Vein graft neointimal hyperplasia. Intervention: Tumor necrosis factor-alpha (TNF) and platelet-derived growth factor (PDGF) vs. Basal/Control. Primary outcome: Smooth muscle cell migration and mitogenesis.

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Key result

In primary rabbit smooth muscle cells, TNF promotes migration and mitogenesis through signaling mechanisms that are both distinct from and overlapping with those employed by PDGF.

Population

Rabbit jugulocarotid interposition vein grafts and primary rabbit aortic smooth muscle cells (SMCs)

Comparison

Tumor necrosis factor-alpha and platelet-derived… vs Basal conditions / untreated cells

Design

Preclinical

Authors

KPKarsten PeppelCSL (United States)LZLisheng ZhangChinese Academy of Medical Sciences & Peking Union Medical College EOEric S. OrmanPDK International

Discussion

Member takes

Implication

TNF and PDGF pathways overlap yet diverge in VSMC migration; hypothesis-generating for vascular remodeling but leaves open in vivo relevance.

Key Points

To determine the molecular mechanisms by which tumor necrosis factor-alpha (TNF) stimulates migration and proliferation in vascular smooth muscle cells, specifically in relation to platelet-derived growth factor (PDGF) signaling.
Evaluated TNF expression in rabbit jugulocarotid interposition vein grafts postoperatively.
Treated cultured rabbit aortic smooth muscle cells with TNF, PDGF, or both, assessing chemotaxis, mitogenesis via [(3)H]thymidine incorporation, and activation of p38 MAPK, ERK1/2, PI3K, and NF-κB using kinase inhibitors (U0126, LY294002) and dominant-negative IκBα.
TNF and PDGF each independently increased smooth muscle cell migration 1.7-fold over basal levels, and while TNF alone failed to promote [(3)H]thymidine incorporation, it doubled PDGF-induced incorporation.
PDGF activated ERK1/2 and PI3K two to three times more strongly than TNF, whereas only TNF activated NF-κB, with dominant-negative IκBα selectively abolishing TNF-dependent mitogenesis.
PI3K inhibition with LY294002 decreased both TNF- and PDGF-induced migration by 38% to 54% (P<0.05), whereas ERK inhibition with U0126 reduced PDGF-stimulated migration by 35% (P<0.05) but did not affect TNF-stimulated migration.

Structured PICO

Population

Rabbit jugulocarotid interposition vein grafts and primary rabbit aortic smooth muscle cells (SMCs)

Intervention

Tumor necrosis factor-alpha (TNF) and platelet-derived growth factor (PDGF) stimulation, with or without inhibitors (U0126, LY294002, dominant-negative I kappa B alpha mutant)

Comparator

Basal conditions / untreated cells

Outcome

Smooth muscle cell migration, mitogenesis ([(3)H]thymidine incorporation), and signal transduction activation (p38mapk, ERK 1/2, PI3K, NF kappa B)surrogate

In primary rabbit smooth muscle cells, TNF promotes migration and mitogenesis through signaling mechanisms that overlap with and are distinct from PDGF, requiring complementary co-stimulation for mitogenesis.

Cite This Study

Peppel et al. (2004) studied Vein graft neointimal hyperplasia. Tumor necrosis factor-alpha (TNF) and platelet-derived growth factor (PDGF) vs. Basal/Control was evaluated on Smooth muscle cell migration and mitogenesis. In primary rabbit smooth muscle cells, TNF promotes migration and mitogenesis through signaling mechanisms that are both distinct from and overlapping with those employed by PDGF.

synapsesocial.com/papers/6a94da2dcf5366e90fd1cf63 https://doi.org/10.1016/j.cardiores.2004.10.031

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Implication

TNF and PDGF pathways overlap yet diverge in VSMC migration; hypothesis-generating for vascular remodeling but leaves open in vivo relevance.

Activation of vascular smooth muscle cells by TNF and PDGF: overlapping and complementary signal transduction mechanisms

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Activation of vascular smooth muscle cells by TNF and PDGF: overlapping and complementary signal transduction mechanisms

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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Also Consider