Peroxisome proliferator-activated receptor delta regulates extracellular matrix and apoptosis of vascular smooth muscle cells through the activation of transforming growth factor-beta1/Smad3. Export

@article{citeulike:6108196, abstract = {Homeostasis of the extracellular matrix and apoptosis of vascular smooth muscle cells (VSMCs) are key components in the regulation of the stability of atherosclerotic plaques. Here, we demonstrate that peroxisome proliferator-activated receptor (PPAR)delta regulates extracellular matrix synthesis and degradation through transforming growth factor-beta1 and its effector, Smad3. Activation of PPARdelta strongly amplified the expression of types I and III collagen, fibronectin, elastin, and TIMP-3 (tissue inhibitor of metalloproteinases 3), but not of TIMP-1, matrix metalloproteinase-2 or -9. The effect of PPARdelta on the expression of type III collagen was dually regulated by the direct binding of PPARdelta and Smad3 to a direct repeat-1 site and a Smad-binding element, respectively, in the type III collagen gene promoter. The activation of PPARdelta attenuated apoptotic cell death in VSMCs induced by oxidized low-density lipoprotein, and similar antiapoptotic effects were observed on treatment of cells with exogenous type I and/or III collagen. Administration of a PPARdelta ligand GW501516 to mice also suppressed elastase-induced cell death of aortic VSMCs. These results suggest that PPARdelta-induced upregulation of extracellular matrix proteins exerts an antiapoptotic effect, thereby maintaining the stability of atherosclerotic plaques. Specific ligands of PPARdelta may aid in the therapeutic intervention of atherosclerosis by improving plaque stability and patient prognosis.}, author = {Kim, Hyo Jung J. and Kim, Min Young Y. and Jin, Hana and Kim, Hyun Joon J. and Kang, Sang Soo S. and Kim, Hye Jung J. and Lee, Jae Heun H. and Chang, Ki Churl C. and Hwang, Jin-Yong Y. and Yabe-Nishimura, Chihiro and Kim, Jin-Hoi H. and Seo, Han Geuk G.}, citeulike-article-id = {6108196}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/CIRCRESAHA.108.189159}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19461048}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19461048}, day = {2}, doi = {10.1161/CIRCRESAHA.108.189159}, issn = {1524-4571}, journal = {Circulation research}, keywords = {apoptosis, ecm, ppar, smad, tgfb, vsmc}, month = {July}, number = {1}, pages = {16--24}, posted-at = {2009-11-13 10:35:18}, priority = {2}, title = {Peroxisome proliferator-activated receptor {delta} regulates extracellular matrix and apoptosis of vascular smooth muscle cells through the activation of transforming growth factor-{beta}1/Smad3.}, url = {http://dx.doi.org/10.1161/CIRCRESAHA.108.189159}, volume = {105}, year = {2009} }

TY - JOUR ID - citeulike:6108196 L3 - citeulike-article-id:6108196 N2 - Homeostasis of the extracellular matrix and apoptosis of vascular smooth muscle cells (VSMCs) are key components in the regulation of the stability of atherosclerotic plaques. Here, we demonstrate that peroxisome proliferator-activated receptor (PPAR)delta regulates extracellular matrix synthesis and degradation through transforming growth factor-beta1 and its effector, Smad3. Activation of PPARdelta strongly amplified the expression of types I and III collagen, fibronectin, elastin, and TIMP-3 (tissue inhibitor of metalloproteinases 3), but not of TIMP-1, matrix metalloproteinase-2 or -9. The effect of PPARdelta on the expression of type III collagen was dually regulated by the direct binding of PPARdelta and Smad3 to a direct repeat-1 site and a Smad-binding element, respectively, in the type III collagen gene promoter. The activation of PPARdelta attenuated apoptotic cell death in VSMCs induced by oxidized low-density lipoprotein, and similar antiapoptotic effects were observed on treatment of cells with exogenous type I and/or III collagen. Administration of a PPARdelta ligand GW501516 to mice also suppressed elastase-induced cell death of aortic VSMCs. These results suggest that PPARdelta-induced upregulation of extracellular matrix proteins exerts an antiapoptotic effect, thereby maintaining the stability of atherosclerotic plaques. Specific ligands of PPARdelta may aid in the therapeutic intervention of atherosclerosis by improving plaque stability and patient prognosis. IS - 1 JF - Circulation research SN - 1524-4571 EP - 24 TI - Peroxisome proliferator-activated receptor {delta} regulates extracellular matrix and apoptosis of vascular smooth muscle cells through the activation of transforming growth factor-{beta}1/Smad3. VL - 105 SP - 16 KW - apoptosis KW - ecm KW - ppar KW - smad KW - tgfb KW - vsmc AU - Kim, Hyo Jung AU - Kim, Min Young AU - Jin, Hana AU - Kim, Hyun Joon AU - Kang, Sang Soo AU - Kim, Hye Jung AU - Lee, Jae Heun AU - Chang, Ki Churl AU - Hwang, Jin-Yong AU - Yabe-Nishimura, Chihiro AU - Kim, Jin-Hoi AU - Seo, Han Geuk PY - 2009/07/02/ UR - http://dx.doi.org/10.1161/CIRCRESAHA.108.189159 ER -