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Hedgehog turns lipoproteins into Janus-faced particles
Maarten F Bijlsma1, C Arnold Spek, Maikel P Peppelenbosch
1Academic Medical Center, Laboratory of Experimental Internal Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Trends in Cardiovascular Medicine
|September 19, 2006
Summary
Hedgehog signaling molecules, previously thought to act locally, are transported by lipoproteins, similar to low-density lipoprotein (LDL). This discovery reveals hedgehog
Area of Science:
- Developmental Biology
- Molecular Biology
- Cardiovascular Research
Background:
- Hedgehog (Hh) proteins are crucial morphogens in embryonic development.
- Hydrophobic components of Hh suggest limited signaling range.
- Hh signaling persists in mammals, aiding tissue repair, like cardiac revascularization.
Purpose of the Study:
- To investigate the transport mechanism of Hh.
- To explore the role of lipoproteins in Hh long-range signaling.
- To understand the implications for cardiovascular disease and LDL function.
Main Methods:
- Research in Drosophila melanogaster to identify Hh transport mechanisms.
- Comparison of insect lipoproteins with mammalian low-density lipoprotein (LDL).
- Review of existing literature on Hh signaling in mammalian development and adult tissue repair.
Main Results:
- Hedgehog can be transported by insect lipoproteins resembling mammalian LDL.
- This lipoprotein-mediated transport enables long-range Hh signaling.
- Hedgehog gene therapy shows efficacy in limiting cardiac damage in rodents.
Conclusions:
- Lipoprotein transport is a key mechanism for long-range hedgehog signaling.
- Mammalian LDL may transport hedgehog, impacting its role in cardiovascular health.
- LDL's role may extend beyond atherosclerosis to tissue repair and salvage via hedgehog.
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