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...
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Published in | Biochemical and biophysical research communications Vol. 302; no. 1; pp. 67 - 72 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
28.02.2003
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Subjects | |
Online Access | Get full text |
ISSN | 0006-291X 1090-2104 |
DOI | 10.1016/S0006-291X(03)00109-8 |
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Abstract | 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. |
---|---|
AbstractList | 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. 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 mu M) increased BMP-2 gene transcription >14-fold as measured by real-time PCR analysis (P0.05 vs. solvent control). Moreover, VSMC proliferation stimulated with native low-density lipoprotein (100 mu g of protein/mL) was prevented by either human recombinant BMP-2 or BMP-7 at concentrations of 100ng/mL (P0.05). Both BMPs also inhibited basal cell proliferation (P0.05). 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. 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.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. 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. |
Author | Ortmann, Jana Doerflinger, Tim Emmanuele, Luca Traupe, Tobias Barton, Matthias |
Author_xml | – sequence: 1 givenname: Luca surname: Emmanuele fullname: Emmanuele, Luca – sequence: 2 givenname: Jana surname: Ortmann fullname: Ortmann, Jana – sequence: 3 givenname: Tim surname: Doerflinger fullname: Doerflinger, Tim – sequence: 4 givenname: Tobias surname: Traupe fullname: Traupe, Tobias – sequence: 5 givenname: Matthias surname: Barton fullname: Barton, Matthias email: barton@usz.ch |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/12593849$$D View this record in MEDLINE/PubMed |
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Keywords | 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 |
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Snippet | Bone morphogenetic proteins (BMPs) stimulate ectopic bone formation in skeletal muscle. Here we show that human vascular smooth muscle cells (VSMC) abundantly... |
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SubjectTerms | 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 |
Title | Lovastatin stimulates human vascular smooth muscle cell expression of bone morphogenetic protein-2, a potent inhibitor of low-density lipoprotein-stimulated cell growth |
URI | https://dx.doi.org/10.1016/S0006-291X(03)00109-8 https://www.ncbi.nlm.nih.gov/pubmed/12593849 https://www.proquest.com/docview/19394336 https://www.proquest.com/docview/73044486 |
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