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February 8, 2011PLoS ONEOpen Access

A Local Proinflammatory Signalling Loop Facilitates Adverse Age-Associated Arterial Remodeling

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Key result

An autocatalytic signaling loop involving MCP-1, MMP-2, and TGF-β1 enhances collagen production and invasiveness of vascular smooth muscle cells, contributing to adverse age-associated arterial remodeling.

Why the study?

Does suppression of the MCP-1/MMP-2/TGF-β1 signaling loop prevent age-associated adverse arterial remodeling in rat VSMCs?

Population

Male Fisher 344 crossbred Brown Norway rats, 8-month-old and 30-month-old, and vascular smooth muscle cells…

Comparison

In vitro treatments including MCP-1, TGF-β1… vs Untreated VSMCs or scramble siRNA controls.

Design

Preclinical

Authors

MWMingyi WangGSGaia SpinettiRMRobert E. Monticone

Discussion

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Member takes

Overview

Suggests a novel target against vascular aging; leaves open therapeutic efficacy pending prospective validation.

Structured PICO

Does suppression of the MCP-1/MMP-2/TGF-β1 signaling loop prevent age-associated adverse arterial remodeling in rat VSMCs?

P
Population
40 male Fisher 344 crossbred Brown Norway rats aged 8 and 30 months used to study the molecular mechanisms of age-associated arterial remodeling.
I
Intervention
In vitro treatments including MCP-1 (1-100 ng/ml), TGF-β1 (1-100 ng/ml), si-MCP-1 (25-50 nM), CCR2 antagonist vCCI (150 ng/ml), and MMP-2 inhibitor GM 6001 (15 μM) or neutralizing antibody.
C
Comparator
Untreated VSMCs or scramble siRNA controls.
O
Outcome
Activation of the MCP-1/MMP-2/TGF-β1 signaling loop, collagen production, and VSMC invasiveness.surrogate

Main Result

p-value: p=<0.05

A local proinflammatory signaling loop involving MCP-1, MMP-2, and TGF-β1 facilitates adverse age-associated arterial remodeling, providing a potential therapeutic target to retard vascular aging.

Limitations

  • In vitro and animal model findings may not fully translate to human arterial aging
  • Complex signaling networks and other suppressive signaling pathways were not fully explored

Cite This Study

Wang et al. (2011) studied Age-associated arterial remodeling (n=40). MCP-1, TGF-b1, and MMP-2 modulation vs. Untreated cells / Young vs Old was evaluated on Vascular smooth muscle cell (VSMC) invasion and collagen production (p=<0.05). An autocatalytic signaling loop involving MCP-1, MMP-2, and TGF-β1 enhances collagen production and invasiveness of vascular smooth muscle cells, contributing to adverse age-associated arterial remodeling.

synapsesocial.com/papers/6a82d03072d82bb027239db8https://doi.org/10.1371/journal.pone.0016653
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function2004 · 177 citations
  2. 2Matrix Metalloproteinase 2 Activation of Transforming Growth Factor-β1 (TGF-β1) and TGF-β1–Type II Receptor Signaling Within the Aged Arterial Wall2006 · 254 citations
  3. 3Proinflammatory Profile Within the Grossly Normal Aged Human Aortic Wall2007 · 267 citations
  4. 4Proinflammation of Aging Central Arteries: A Mini-Review2014 · 41 citations
  5. 5Central Arterial Aging and Angiotensin II Signaling2010 · 92 citations