The nuclear receptor, PPARgamma, interacts with the transmembrane receptor LRP1 in vascular smooth muscle cells to help protect against calcified lesions of mouse arteries that resemble those found in humans. The finding, reported in Nature Communications this week, reveals a novel regulatory mechanism that is required for maintaining the integrity of blood vessels and could prove useful in the development of treatment of vascular disease.
Calcification of blood vessels is implicated in heart disease. Although the mechanisms that lead to calcification are not fully understood, they are believed to involve the transmebrane receptor LRP1, which engages Wnt signalling pathways. Phillippe Boucher and colleagues generate mice lacking PPAR gamma - in their blood vessels and show that this increases atherosclerosis susceptibility and enhanced Wnt signalling due to reduced activation of LRP1.
The authors suggest that their findings may have important clinical implications because selective PPARgamma blockers may be therapeutically effective in the treatment and prevention of atherosclerosis.