Lovastatin stimulates human vascular smooth muscle cell expression of bone morphogenetic protein-2, a potent inhibitor of low-density lipoprotein-stimulated cell growth.
Bone morphogenetic proteins (BMPs) stimulate ectopic bone formation in skeletal muscle. Here we show that human vascular smooth muscle cells (VSMC) abundantly express mRNA encoding for BMP receptor type II, BMP-2, and BMP-7 proteins. Treatment with the 3-hydroxy-3-methylglutaryl coenzyme A inhibitor lovastatin (34 microM) increased BMP-2 gene transcription >14-fold as measured by real-time PCR analysis (P<0.05 vs. solvent control). Moreover, VSMC proliferation stimulated with native low-density lipoprotein (100 microg of protein/mL) was prevented by either human recombinant BMP-2 or BMP-7 at concentrations of 100 ng/mL (P<0.05). Both BMPs also inhibited basal cell proliferation (P<0.05). Induction of BMPs and subsequent inhibition of VSMC growth and/or induction of vascular bone formation could contribute to the mechanisms by which statins increase plaque stability in patients with coronary atherosclerosis.
Emmanuele
Luca
L
Department of Internal Medicine, Medical Policlinic, University Hospital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland.
Ortmann
Jana
J
Doerflinger
Tim
T
Traupe
Tobias
T
Barton
Matthias
M
D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000502:physiology*; D008148:Lovastatin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D008148:Lovastatin