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Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast
Abstract:
Proliferation of smooth muscle cells (SMCs) represents an important event in vascular lesion formation. Despite the common belief that growth factors contribute to the development of the atherosclerotic plaque, until now there has been no direct evidence for a role of mitogens in the development of arterial lesions. Balloon catheter injury of the rat carotid artery is accompanied by death of medial SMCs and is typically followed by proliferation of SMCs with subsequent formation of an intimal lesion. Our hypothesis is that injury causes mitogens to be released from dead cells, which then stimulate cell proliferation. One such mitogen that may be important in this process is basic fibroblast growth factor (bFGF), which can be detected immunocytochemically in SMCs and endothelial cells of adult rat carotid arteries. Systemic injection of a neutralizing antibody against bFGF prior to balloon catheterization significantly decreased the induced SMC proliferation by approximately 80%. The intimal lesion that developed within 8 days after injury, however, was not significantly reduced. The results of this study support the concept that endogenous bFGF is the major mitogen controlling the growth of vascular smooth muscle cells following injury. These data may have implications for the observed failure of endarterectomy and angioplasty procedures.
Insights
Injury to arteries triggers the release of basic fibroblast growth factor (bFGF), a key mitogen that drives smooth muscle cell proliferation. Neutralizing bFGF significantly reduced cell growth but not lesion size, suggesting complex roles in vascular repair.
Area of Science:
- Vascular Biology
- Cellular Proliferation
- Atherosclerosis Research
Background:
- Smooth muscle cell (SMC) proliferation is crucial in vascular lesion development.
- Growth factors' role in atherosclerotic plaque formation lacked direct evidence.
- Arterial injury models show SMC death followed by proliferation and intimal lesion formation.
Purpose of the Study:
- To investigate the role of mitogens, specifically basic fibroblast growth factor (bFGF), in SMC proliferation after arterial injury.
- To test the hypothesis that injury-induced cell death releases mitogens that stimulate SMC proliferation.
Main Methods:
- Balloon catheter injury was performed on rat carotid arteries.
- Systemic injection of a neutralizing antibody against bFGF was administered before injury.
- SMC proliferation and intimal lesion formation were quantified 8 days post-injury.
Main Results:
- Neutralizing bFGF significantly decreased induced SMC proliferation by approximately 80%.
- The development of the intimal lesion 8 days after injury was not significantly reduced by bFGF neutralization.
- Endogenous bFGF was detected immunocytochemically in SMCs and endothelial cells of healthy arteries.
Conclusions:
- Endogenous bFGF is a major mitogen controlling vascular SMC growth post-injury.
- These findings may have implications for understanding the outcomes of endarterectomy and angioplasty.
- While bFGF drives proliferation, its role in complete lesion formation requires further investigation.