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Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy.
Circulation. 2004 Mar 23; 109(11):1392-400.Circ

Abstract

BACKGROUND

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists inhibit vascular smooth muscle proliferation and migration and improve endothelial function. It is unknown whether PPAR-gamma agonists favorably modulate bone marrow (BM)-derived angiogenic progenitor cells (APCs) to promote endothelial lineage differentiation and early reendothelialization after vascular intervention.

METHODS AND RESULTS

C57/BL6 mice, treated with or without rosiglitazone (8 mg/kg per day), a PPAR-gamma agonist, underwent femoral angioplasty. Rosiglitazone treatment attenuated neointimal formation (intima/media ratio: 0.98+/-0.12 [rosiglitazone] versus 3.1+/-0.5 [control]; P<0.001; n=10 per group). Using a BM transplantation model, we identified that 58+/-12% of the cells within the neointima at 4 weeks were derived from the BM. Pure endothelial marker-positive, pure alpha-smooth muscle actin (alphaSMA)-positive, or double-positive APCs could be found both in mouse BM and in human peripheral blood after culture in conditional medium enriched with vascular endothelial growth factor. Rosiglitazone caused a 6-fold (P<0.001) increase in colony formation by human endothelial progenitor cells, promoted the differentiation of APCs toward the endothelial lineage in mouse BM in vivo (0.66+/-0.06% [control] to 0.95+/-0.08% [rosiglitazone]; P<0.05) and in human peripheral blood in vitro (13.2+/-1.5% [control] to 28.4+/-3.3% [rosiglitazone]; P<0.05), and inhibited the differentiation toward the smooth muscle cell lineage. Within the neointima, rosiglitazone also stimulated APCs to differentiate into mature endothelial cells and caused earlier reendothelialization compared with controls (31+/-5 versus 8+/-2 CD31-positive cells per millimeter of neointimal surface on day 14; P<0.01).

CONCLUSIONS

Similar to embryonic stem cell-derived progenitors, the adult BM and peripheral blood harbor APCs that are at least bipotential and able to differentiate into endothelial and smooth muscle lineages. The PPAR-gamma agonist rosiglitazone promotes the differentiation of these APCs toward the endothelial lineage and attenuates restenosis after angioplasty.

Authors+Show Affiliations

Division of Cardiac Surgery, Toronto General Hospital, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14993120

Citation

Wang, Chao-Hung, et al. "Rosiglitazone Facilitates Angiogenic Progenitor Cell Differentiation Toward Endothelial Lineage: a New Paradigm in Glitazone Pleiotropy." Circulation, vol. 109, no. 11, 2004, pp. 1392-400.
Wang CH, Ciliberti N, Li SH, et al. Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy. Circulation. 2004;109(11):1392-400.
Wang, C. H., Ciliberti, N., Li, S. H., Szmitko, P. E., Weisel, R. D., Fedak, P. W., Al-Omran, M., Cherng, W. J., Li, R. K., Stanford, W. L., & Verma, S. (2004). Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy. Circulation, 109(11), 1392-400.
Wang CH, et al. Rosiglitazone Facilitates Angiogenic Progenitor Cell Differentiation Toward Endothelial Lineage: a New Paradigm in Glitazone Pleiotropy. Circulation. 2004 Mar 23;109(11):1392-400. PubMed PMID: 14993120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy. AU - Wang,Chao-Hung, AU - Ciliberti,Nadia, AU - Li,Shu-Hong, AU - Szmitko,Paul E, AU - Weisel,Richard D, AU - Fedak,Paul W M, AU - Al-Omran,Mohammed, AU - Cherng,Wen-Jin, AU - Li,Ren-Ke, AU - Stanford,William L, AU - Verma,Subodh, Y1 - 2004/03/01/ PY - 2004/3/3/pubmed PY - 2004/7/9/medline PY - 2004/3/3/entrez SP - 1392 EP - 400 JF - Circulation JO - Circulation VL - 109 IS - 11 N2 - BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists inhibit vascular smooth muscle proliferation and migration and improve endothelial function. It is unknown whether PPAR-gamma agonists favorably modulate bone marrow (BM)-derived angiogenic progenitor cells (APCs) to promote endothelial lineage differentiation and early reendothelialization after vascular intervention. METHODS AND RESULTS: C57/BL6 mice, treated with or without rosiglitazone (8 mg/kg per day), a PPAR-gamma agonist, underwent femoral angioplasty. Rosiglitazone treatment attenuated neointimal formation (intima/media ratio: 0.98+/-0.12 [rosiglitazone] versus 3.1+/-0.5 [control]; P<0.001; n=10 per group). Using a BM transplantation model, we identified that 58+/-12% of the cells within the neointima at 4 weeks were derived from the BM. Pure endothelial marker-positive, pure alpha-smooth muscle actin (alphaSMA)-positive, or double-positive APCs could be found both in mouse BM and in human peripheral blood after culture in conditional medium enriched with vascular endothelial growth factor. Rosiglitazone caused a 6-fold (P<0.001) increase in colony formation by human endothelial progenitor cells, promoted the differentiation of APCs toward the endothelial lineage in mouse BM in vivo (0.66+/-0.06% [control] to 0.95+/-0.08% [rosiglitazone]; P<0.05) and in human peripheral blood in vitro (13.2+/-1.5% [control] to 28.4+/-3.3% [rosiglitazone]; P<0.05), and inhibited the differentiation toward the smooth muscle cell lineage. Within the neointima, rosiglitazone also stimulated APCs to differentiate into mature endothelial cells and caused earlier reendothelialization compared with controls (31+/-5 versus 8+/-2 CD31-positive cells per millimeter of neointimal surface on day 14; P<0.01). CONCLUSIONS: Similar to embryonic stem cell-derived progenitors, the adult BM and peripheral blood harbor APCs that are at least bipotential and able to differentiate into endothelial and smooth muscle lineages. The PPAR-gamma agonist rosiglitazone promotes the differentiation of these APCs toward the endothelial lineage and attenuates restenosis after angioplasty. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/14993120/Rosiglitazone_facilitates_angiogenic_progenitor_cell_differentiation_toward_endothelial_lineage:_a_new_paradigm_in_glitazone_pleiotropy_ L2 - https://www.ahajournals.org/doi/10.1161/01.CIR.0000123231.49594.21?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -