Trends Cardiovasc Med 2006 Oct;16(7):217-20
Academic Medical Center, Laboratory of Experimental Internal Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Hedgehog is an important morphogenetic signal during embryonic development. The molecule contains several hydrophobic moieties, including cholesterol and palmitoyl groups, apparently incompatible with long-range functioning. Very recent research, however, performed in the fruitfly Drosophila melanogaster, demonstrated that hedgehog can be carried by insect lipoproteins which strongly resemble mammalian low-density lipoprotein (LDL), enabling the morphogen to act at long distances from its source. Such long-range signaling of hedgehog is in perfect agreement with current insight that in mammals hedgehog signaling is not terminated after gestation has been completed but remains active throughout life, mediating among others revascularization of adult ischemic cardiac tissue. In agreement, hedgehog gene therapy is highly effective in experimental rodents for limiting the damage after coronary occlusion. If indeed hedgehog is transported on lipoproteins in mammals, an interesting change of paradigm might emerge for LDL. No longer would LDL merely be bad news for the progression of atherosclerotic plaques, as it also conveys a revascularization and tissue salvage signal in the form of hedgehog.