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Rebuilding the coronary vasculature: hedgehog as a new candidate for pharmacologic revascularization
Kory J Lavine1, David M Ornitz
1Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA. lavinek@msnotes.wustl.edu
Insights
Hedgehog signaling shows promise for treating ischemic heart disease by promoting new blood vessel growth. This noninvasive approach offers hope for patients unresponsive to traditional therapies.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Molecular Biology
Background:
- Ischemic heart disease and myocardial infarction are leading causes of death globally.
- Current treatments like surgery have limitations, leaving many patients with suboptimal outcomes.
- There is a critical need for noninvasive therapies to restore coronary blood flow.
Purpose of the Study:
- To review the role of the hedgehog signaling pathway in coronary vascular development and growth.
- To evaluate hedgehog as a novel therapeutic candidate for ischemic heart disease.
- To discuss the potential of therapeutic revascularization using proangiogenic factors.
Main Methods:
- Review of existing literature on proangiogenic factors for therapeutic revascularization.
- Analysis of studies investigating fibroblast growth factor and vascular endothelial growth factor.
- Examination of recent findings on the hedgehog pathway's role in vascular growth.
Main Results:
- Fibroblast growth factor and vascular endothelial growth factor have shown limited clinical success despite animal model efficacy.
- The hedgehog pathway has emerged as a potent promoter of coronary vascular growth.
- Hedgehog signaling is essential for both developmental and adult coronary vasculature formation.
Conclusions:
- The hedgehog pathway represents a promising new target for therapeutic revascularization in ischemic heart disease.
- Noninvasive strategies utilizing hedgehog signaling could offer improved treatment options.
- Further research into hedgehog's clinical application is warranted for patients ineligible for conventional therapies.
Abstract:
Myocardial infarction and ischemic heart disease are among the most common causes of morbidity and mortality in the industrial world. Surgical and percutaneous intravascular approaches are commonly used to treat these diseases. Regrettably, a significant number of patients are either ineligible or demonstrate suboptimal responses to these therapies. In an attempt to provide such patients improved therapeutic options, much effort has been spent developing noninvasive approaches to restore coronary vascular perfusion. One such strategy, termed therapeutic revascularization or angiogenesis, involves administration of proangiogenic factors, which improve coronary perfusion by promoting growth of the coronary vasculature. Thus far, two potential proangiogenic factors have been intensively examined, fibroblast growth factor and vascular endothelial growth factor. Unfortunately, despite their apparent efficacy in animal models, neither factor has performed adequately in the clinic to date. Within the past year a new factor, hedgehog, has been shown to effectively promote the growth of the coronary vasculature and thus has been proposed as a novel candidate for therapeutic revascularization. In this review, we discuss the discovery of the hedgehog pathway as an essential regulator of the development of the coronary vasculature, as an inducer of adult coronary vascular growth, and as a therapeutic in the treatment of ischemic heart disease.
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