Lovastatin stimulates human vascular smooth muscle cell expression of bone morphogenetic protein-2, a potent inhibitor of low-density lipoprotein-stimulated cell growth

• Published in: Biochemical and biophysical research communications Vol. 302; no. 1; pp. 67 - 72
• Main Authors: Emmanuele, Luca, Ortmann, Jana, Doerflinger, Tim, Traupe, Tobias, Barton, Matthias
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.02.2003
• Subjects: Base Sequence; BMP-statins; Bone; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - physiology; Cell Division - physiology; Cholesterol; DNA Primers; Gene Expression Regulation - drug effects; HMG-CoA reductase inhibitor; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Lipoproteins, LDL - physiology; Lovastatin - pharmacology; Low-density lipoprotein; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Plaque rupture; Recombinant Proteins; Reverse transcriptase polymerase chain reaction; Risk factors; RNA, Messenger - genetics; Thymidine incorporation; Transforming Growth Factor beta; Transforming growth factor-β; Low-density lipoprotein; Plaque rupture; BMP-statins; Thymidine incorporation; Reverse transcriptase polymerase chain reaction; HMG-CoA reductase inhibitor; Transforming growth factor-β; Bone; Risk factors; Cholesterol
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(03)00109-8

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 μM) 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 μg 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.