|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 |
|Date or Month Published||2006 Jan |
|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. |
|Alternate Journal||J. Vasc. Surg. |
|Citation Key||1882 |
|PubMed ID||16414402 |