Vascular Smooth Muscle Cell Apoptosis Promotes Transplant Arteriosclerosis Through Inducing the Production of SDF-1α.
Summary of "Vascular Smooth Muscle Cell Apoptosis Promotes Transplant Arteriosclerosis Through Inducing the Production of SDF-1α."
Transplant arteriosclerosis is a leading cause of late allograft loss. Medial smooth muscle cell (SMC) apoptosis is considered to be an important event in transplant arteriosclerosis. However, the precise contribution of medial SMC apoptosis to transplant arteriosclerosis and the underlying mechanisms remain unclear. We transferred wild-type p53 to induce apoptosis of cultured SMCs. We found that apoptosis induces the production of SDF-1α from apoptotic and neighboring viable cells, resulting in increased SDF-1α in the culture media. Conditioned media from Ltv-p53-transferred SMCs activated PI3K/Akt/mTOR and MAPK/Erk signaling in a SDF-1α-dependent manner and thereby promoted mesenchymal stem cell (MSC) migration and proliferation. In a rat aorta transplantation model, lentivirus-mediated BclxL transfer selectively inhibits medial SMC apoptosis in aortic allografts, resulting in a remarkable decrease of SDF-1α both in allograft media and in blood plasma, associated with diminished recruitment of CD90(+) CD105(+) double-positive cells and impaired neointimal formation. Systemic administration of rapamycin or PD98059 also attenuated MSC recruitment and neointimal formation in the aortic allografts. These results suggest that medial SMC apoptosis is critical for the development of transplant arteriosclerosis through inducing SDF-1α production and that MSC recruitment represents a major component of vascular remodeling, constituting a relevant target and mechanism for therapeutic interventions.
Affiliation
Division of Liver Transplantation, Department of General Surgery Departments of Gerontology Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Journal Details
This article was published in the following journal.
Name: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Tr
ISSN: 1600-6143
Pages: 2029-43
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22845908
- DOI: http://dx.doi.org/10.1111/j.1600-6143.2012.04082.x
Medical and Biotech [MESH] Definitions
Gata6 Transcription Factor
A GATA transcription factor that is expressed predominately in SMOOTH MUSCLE CELLS and regulates vascular smooth muscle CELL DIFFERENTIATION.
Isoxsuprine
A beta-adrenergic agonist that causes direct relaxation of uterine and vascular smooth muscle. Its vasodilating actions are greater on the arteries supplying skeletal muscle than on those supplying skin. It is used in the treatment of peripheral vascular disease and in premature labor.
Muscle, Smooth, Vascular
The nonstriated, involuntary muscle tissue of blood vessels.
Apoptosis Inducing Factor
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
Myoblasts, Smooth Muscle
Precursor cells destined to differentiate into smooth muscle myocytes (MYOCYTES, SMOOTH MUSCLE).
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