| Title | Bone morphogenetic protein 4: potential regulator of shear stress-induced graft neointimal atrophy. |
| Publication Type | Journal Article |
| Year of Publication | 2006 |
| Authors | Hsieh PCH, Kenagy RD, Mulvihill ER, Jeanette JP, Wang X, Chang CMC, Yao Z, Ruzzo WL, Justice S, Hudkins KL, Alpers CE, Berceli S, Clowes AW |
| Journal | Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter |
| Volume | 43 |
| Issue | 1 |
| Pagination | 150-8 |
| Date or Month Published | 2006 Jan |
| ISSN | 0741-5214 |
| Keywords | Animals, Atrophy, Blood Vessel Prosthesis, Bone Morphogenetic Protein 4, Bone Morphogenetic Proteins, Male, Papio, Shear Strength, Stress, Mechanical, Tunica Intima |
| Abstract | OBJECTIVE: Placement in baboons of a distal femoral arteriovenous fistula increases shear stress through aortoiliac polytetrafluoroethylene (PTFE) grafts and induces regression of a preformed neointima. Atrophy of the neointima might be controlled by shear stress-induced genes, including the bone morphogenetic proteins (BMPs). We have investigated the expression and function of BMPs 2, 4, and 5 in the graft neointima and in cultured baboon smooth muscle cells (SMCs).
METHODS: Baboons received bilateral aortoiliac PTFE grafts and 8 weeks later, a unilateral femoral arteriovenous fistula.
RESULTS: Quantitative polymerase chain reaction showed that high shear stress increased BMP2, 4, and 5 messenger RNA (mRNA) in graft intima between 1 and 7 days, while noggin (a BMP inhibitor) mRNA was decreased. BMP4 most potently (60% inhibition) inhibited platelet-derived growth factor-stimulated SMC proliferation compared with BMP2 and BMP5 (31% and 26%, respectively). BMP4 also increased SMC death by 190% +/- 10%. Noggin reversed the antiproliferative and proapoptotic effects of BMP4. Finally, Western blotting confirmed BMP4 protein upregulation by high shear stress at 4 days. BMP4 expression demonstrated by in situ hybridization was confined to endothelial cells.
CONCLUSIONS: Increased BMPs (particularly BMP4) coupled with decreased noggin may promote high shear stress-mediated graft neointimal atrophy by inhibiting SMC proliferation and increasing SMC death. |
| DOI | 10.1016/j.jvs.2005.08.008 |
| Downloads | http://www.ncbi.nlm.nih.gov/pubmed/16414402?dopt=Abstract |
| Alternate Journal | J. Vasc. Surg. |
| Citation Key | 1882 |
| PubMed ID | 16414402 |
