Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Inhibits Vascular Calcification Through Sirtuin 3-Mediated Reduction of Mitochondrial Oxidative Stress
Vascular calcification is associated with cardiovascular death in patients with chronic kidney disease (CKD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) plays an important role in various cardiovascular diseases. However, its role in vascular calcification remains unknown....
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| Veröffentlicht in: | Antioxidants & redox signaling 2019-07, Vol.31 (1), p.75-91 |
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| creator | Feng, Han Wang, Jin-Yu Yu, Bo Cong, Xin Zhang, Wei-Guang Li, Li Liu, Li-Mei Zhou, Yun Zhang, Cheng-Lin Gu, Pei-Liang Wu, Li-Ling |
| description | Vascular calcification is associated with cardiovascular death in patients with chronic kidney disease (CKD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) plays an important role in various cardiovascular diseases. However, its role in vascular calcification remains unknown.
Adenine-induced rat CKD model was used to induce arterial medial calcification. The level of PGC-1α decreased in abdominal aorta of CKD rats. Overexpression of PGC-1α significantly ameliorated calcium deposition in rat abdominal aorta, isolated carotid rings, and cultured vascular smooth muscle cells (VSMCs). Mitochondrial reactive oxygen species (mtROS) increased in calcifying aorta and VSMCs. Upregulation of PGC-1α inhibited, whereas PGC-1α depletion promoted β-glycerophosphate-induced mtROS production and calcium deposition. Moreover, PGC-1α increased superoxide dismutase 1 (SOD1) and SOD2 contents
and
, whereas SOD2 deletion eliminated PGC-1α-mediated mtROS change and promoted calcium deposition. Mechanistically, sirtuin 3 (SIRT3) expression declined in calcifying aorta and VSMCs, while PGC-1α overexpression restored SIRT3 expression. Inhibition of SIRT3 by 3-TYP or siRNA (small interfering RNA) reduced PGC-1α-induced upregulation of SOD1 and SOD2, and abolished the protective effect of PGC-1α on calcification of VSMCs. Importantly, PGC-1α was reduced in calcified femoral arteries in CKD patients. In phosphate-induced human umbilical arterial calcification, upregulation of PGC-1α attenuated calcium nodule formation, while this protective effect was abolished by SIRT3 inhibitor.
We showed for the first time that PGC-1α is an important endogenous regulator against vascular calcification. Induction of PGC-1α could be a potential strategy to treat vascular calcification in CKD patients.
PGC-1α protected against vascular calcification by SIRT3-mediated mtROS reduction. |
| doi_str_mv | 10.1089/ars.2018.7620 |
| format | Article |
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Adenine-induced rat CKD model was used to induce arterial medial calcification. The level of PGC-1α decreased in abdominal aorta of CKD rats. Overexpression of PGC-1α significantly ameliorated calcium deposition in rat abdominal aorta, isolated carotid rings, and cultured vascular smooth muscle cells (VSMCs). Mitochondrial reactive oxygen species (mtROS) increased in calcifying aorta and VSMCs. Upregulation of PGC-1α inhibited, whereas PGC-1α depletion promoted β-glycerophosphate-induced mtROS production and calcium deposition. Moreover, PGC-1α increased superoxide dismutase 1 (SOD1) and SOD2 contents
and
, whereas SOD2 deletion eliminated PGC-1α-mediated mtROS change and promoted calcium deposition. Mechanistically, sirtuin 3 (SIRT3) expression declined in calcifying aorta and VSMCs, while PGC-1α overexpression restored SIRT3 expression. Inhibition of SIRT3 by 3-TYP or siRNA (small interfering RNA) reduced PGC-1α-induced upregulation of SOD1 and SOD2, and abolished the protective effect of PGC-1α on calcification of VSMCs. Importantly, PGC-1α was reduced in calcified femoral arteries in CKD patients. In phosphate-induced human umbilical arterial calcification, upregulation of PGC-1α attenuated calcium nodule formation, while this protective effect was abolished by SIRT3 inhibitor.
We showed for the first time that PGC-1α is an important endogenous regulator against vascular calcification. Induction of PGC-1α could be a potential strategy to treat vascular calcification in CKD patients.
PGC-1α protected against vascular calcification by SIRT3-mediated mtROS reduction.</description><identifier>ISSN: 1523-0864</identifier><identifier>EISSN: 1557-7716</identifier><identifier>DOI: 10.1089/ars.2018.7620</identifier><identifier>PMID: 30829051</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Adenine ; Aorta ; Arteries ; Arteriosclerosis ; Calcification ; Calcification (ectopic) ; Calcium ; Cardiovascular diseases ; Clonal deletion ; Coronary vessels ; Depletion ; Deposition ; Femoral artery ; Femur ; Gene expression ; Glycerophosphate ; Heart diseases ; Kidney diseases ; Mitochondria ; Muscles ; Nodules ; Oxidative stress ; Reactive oxygen species ; Reduction ; siRNA ; Smooth muscle ; Superoxide dismutase</subject><ispartof>Antioxidants & redox signaling, 2019-07, Vol.31 (1), p.75-91</ispartof><rights>Copyright Mary Ann Liebert, Inc. Jul 1, 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c321t-2201df72d417310015f01aa8ebc3258a28fa8242f2a42e30e740a3473ebcd4b33</citedby><cites>FETCH-LOGICAL-c321t-2201df72d417310015f01aa8ebc3258a28fa8242f2a42e30e740a3473ebcd4b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30829051$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Feng, Han</creatorcontrib><creatorcontrib>Wang, Jin-Yu</creatorcontrib><creatorcontrib>Yu, Bo</creatorcontrib><creatorcontrib>Cong, Xin</creatorcontrib><creatorcontrib>Zhang, Wei-Guang</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Liu, Li-Mei</creatorcontrib><creatorcontrib>Zhou, Yun</creatorcontrib><creatorcontrib>Zhang, Cheng-Lin</creatorcontrib><creatorcontrib>Gu, Pei-Liang</creatorcontrib><creatorcontrib>Wu, Li-Ling</creatorcontrib><title>Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Inhibits Vascular Calcification Through Sirtuin 3-Mediated Reduction of Mitochondrial Oxidative Stress</title><title>Antioxidants & redox signaling</title><addtitle>Antioxid Redox Signal</addtitle><description>Vascular calcification is associated with cardiovascular death in patients with chronic kidney disease (CKD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) plays an important role in various cardiovascular diseases. However, its role in vascular calcification remains unknown.
Adenine-induced rat CKD model was used to induce arterial medial calcification. The level of PGC-1α decreased in abdominal aorta of CKD rats. Overexpression of PGC-1α significantly ameliorated calcium deposition in rat abdominal aorta, isolated carotid rings, and cultured vascular smooth muscle cells (VSMCs). Mitochondrial reactive oxygen species (mtROS) increased in calcifying aorta and VSMCs. Upregulation of PGC-1α inhibited, whereas PGC-1α depletion promoted β-glycerophosphate-induced mtROS production and calcium deposition. Moreover, PGC-1α increased superoxide dismutase 1 (SOD1) and SOD2 contents
and
, whereas SOD2 deletion eliminated PGC-1α-mediated mtROS change and promoted calcium deposition. Mechanistically, sirtuin 3 (SIRT3) expression declined in calcifying aorta and VSMCs, while PGC-1α overexpression restored SIRT3 expression. Inhibition of SIRT3 by 3-TYP or siRNA (small interfering RNA) reduced PGC-1α-induced upregulation of SOD1 and SOD2, and abolished the protective effect of PGC-1α on calcification of VSMCs. Importantly, PGC-1α was reduced in calcified femoral arteries in CKD patients. In phosphate-induced human umbilical arterial calcification, upregulation of PGC-1α attenuated calcium nodule formation, while this protective effect was abolished by SIRT3 inhibitor.
We showed for the first time that PGC-1α is an important endogenous regulator against vascular calcification. Induction of PGC-1α could be a potential strategy to treat vascular calcification in CKD patients.
PGC-1α protected against vascular calcification by SIRT3-mediated mtROS reduction.</description><subject>Adenine</subject><subject>Aorta</subject><subject>Arteries</subject><subject>Arteriosclerosis</subject><subject>Calcification</subject><subject>Calcification (ectopic)</subject><subject>Calcium</subject><subject>Cardiovascular diseases</subject><subject>Clonal deletion</subject><subject>Coronary vessels</subject><subject>Depletion</subject><subject>Deposition</subject><subject>Femoral artery</subject><subject>Femur</subject><subject>Gene expression</subject><subject>Glycerophosphate</subject><subject>Heart diseases</subject><subject>Kidney diseases</subject><subject>Mitochondria</subject><subject>Muscles</subject><subject>Nodules</subject><subject>Oxidative stress</subject><subject>Reactive oxygen species</subject><subject>Reduction</subject><subject>siRNA</subject><subject>Smooth muscle</subject><subject>Superoxide dismutase</subject><issn>1523-0864</issn><issn>1557-7716</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpdkc1uEzEQxy1ERUvhyBVZ4tLLpvZ4N3aOVcRHpVataOFqTfxBXG3WwfZW7fvwAoj36DPhJYEDJ49nfv5r5B8hbzibcaYWp5jyDBhXMzkH9owc8a6TjZR8_nyqQTRMzdtD8jLnO8YYcM5ekEPBFCxYx4_Ij2uX4kPIcePodYp98C5hiak5MyXcY3GWfnbGbafW0y-6jLjr1yt_-knPh3VYhZLpV8xm7DHRJfYm-GCwhDjQ23WK47c1vQmpjGGgorl0Nuxj7Wj-QNHTy1CiWcfBpoA9vXoItr6_d_SmJJfzK3Lgsc_u9f48Jl8-vL9dfmourj6eL88uGiOAlwbqP1gvwbZcCs4Y7zzjiMqt6rxTCMqjghY8YAtOMCdbhqKVogK2XQlxTE52udsUv48uF70J2bi-x8HFMWvgSi46xVtW0Xf_oXdxTEPdTgOA4gCLbqKaHWVSzDk5r7cpbDA9as70pE9XfXrSpyd9lX-7Tx1XG2f_0X99id-H1JmP</recordid><startdate>20190701</startdate><enddate>20190701</enddate><creator>Feng, Han</creator><creator>Wang, Jin-Yu</creator><creator>Yu, Bo</creator><creator>Cong, Xin</creator><creator>Zhang, Wei-Guang</creator><creator>Li, Li</creator><creator>Liu, Li-Mei</creator><creator>Zhou, Yun</creator><creator>Zhang, Cheng-Lin</creator><creator>Gu, Pei-Liang</creator><creator>Wu, Li-Ling</creator><general>Mary Ann Liebert, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20190701</creationdate><title>Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Inhibits Vascular Calcification Through Sirtuin 3-Mediated Reduction of Mitochondrial Oxidative Stress</title><author>Feng, Han ; Wang, Jin-Yu ; Yu, Bo ; Cong, Xin ; Zhang, Wei-Guang ; Li, Li ; Liu, Li-Mei ; Zhou, Yun ; Zhang, Cheng-Lin ; Gu, Pei-Liang ; Wu, Li-Ling</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c321t-2201df72d417310015f01aa8ebc3258a28fa8242f2a42e30e740a3473ebcd4b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenine</topic><topic>Aorta</topic><topic>Arteries</topic><topic>Arteriosclerosis</topic><topic>Calcification</topic><topic>Calcification (ectopic)</topic><topic>Calcium</topic><topic>Cardiovascular diseases</topic><topic>Clonal deletion</topic><topic>Coronary vessels</topic><topic>Depletion</topic><topic>Deposition</topic><topic>Femoral artery</topic><topic>Femur</topic><topic>Gene expression</topic><topic>Glycerophosphate</topic><topic>Heart diseases</topic><topic>Kidney diseases</topic><topic>Mitochondria</topic><topic>Muscles</topic><topic>Nodules</topic><topic>Oxidative stress</topic><topic>Reactive oxygen species</topic><topic>Reduction</topic><topic>siRNA</topic><topic>Smooth muscle</topic><topic>Superoxide dismutase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Feng, Han</creatorcontrib><creatorcontrib>Wang, Jin-Yu</creatorcontrib><creatorcontrib>Yu, Bo</creatorcontrib><creatorcontrib>Cong, Xin</creatorcontrib><creatorcontrib>Zhang, Wei-Guang</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Liu, Li-Mei</creatorcontrib><creatorcontrib>Zhou, Yun</creatorcontrib><creatorcontrib>Zhang, Cheng-Lin</creatorcontrib><creatorcontrib>Gu, Pei-Liang</creatorcontrib><creatorcontrib>Wu, Li-Ling</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Antioxidants & redox signaling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Feng, Han</au><au>Wang, Jin-Yu</au><au>Yu, Bo</au><au>Cong, Xin</au><au>Zhang, Wei-Guang</au><au>Li, Li</au><au>Liu, Li-Mei</au><au>Zhou, Yun</au><au>Zhang, Cheng-Lin</au><au>Gu, Pei-Liang</au><au>Wu, Li-Ling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Inhibits Vascular Calcification Through Sirtuin 3-Mediated Reduction of Mitochondrial Oxidative Stress</atitle><jtitle>Antioxidants & redox signaling</jtitle><addtitle>Antioxid Redox Signal</addtitle><date>2019-07-01</date><risdate>2019</risdate><volume>31</volume><issue>1</issue><spage>75</spage><epage>91</epage><pages>75-91</pages><issn>1523-0864</issn><eissn>1557-7716</eissn><abstract>Vascular calcification is associated with cardiovascular death in patients with chronic kidney disease (CKD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) plays an important role in various cardiovascular diseases. However, its role in vascular calcification remains unknown.
Adenine-induced rat CKD model was used to induce arterial medial calcification. The level of PGC-1α decreased in abdominal aorta of CKD rats. Overexpression of PGC-1α significantly ameliorated calcium deposition in rat abdominal aorta, isolated carotid rings, and cultured vascular smooth muscle cells (VSMCs). Mitochondrial reactive oxygen species (mtROS) increased in calcifying aorta and VSMCs. Upregulation of PGC-1α inhibited, whereas PGC-1α depletion promoted β-glycerophosphate-induced mtROS production and calcium deposition. Moreover, PGC-1α increased superoxide dismutase 1 (SOD1) and SOD2 contents
and
, whereas SOD2 deletion eliminated PGC-1α-mediated mtROS change and promoted calcium deposition. Mechanistically, sirtuin 3 (SIRT3) expression declined in calcifying aorta and VSMCs, while PGC-1α overexpression restored SIRT3 expression. Inhibition of SIRT3 by 3-TYP or siRNA (small interfering RNA) reduced PGC-1α-induced upregulation of SOD1 and SOD2, and abolished the protective effect of PGC-1α on calcification of VSMCs. Importantly, PGC-1α was reduced in calcified femoral arteries in CKD patients. In phosphate-induced human umbilical arterial calcification, upregulation of PGC-1α attenuated calcium nodule formation, while this protective effect was abolished by SIRT3 inhibitor.
We showed for the first time that PGC-1α is an important endogenous regulator against vascular calcification. Induction of PGC-1α could be a potential strategy to treat vascular calcification in CKD patients.
PGC-1α protected against vascular calcification by SIRT3-mediated mtROS reduction.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>30829051</pmid><doi>10.1089/ars.2018.7620</doi><tpages>17</tpages></addata></record> |
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| subjects | Adenine Aorta Arteries Arteriosclerosis Calcification Calcification (ectopic) Calcium Cardiovascular diseases Clonal deletion Coronary vessels Depletion Deposition Femoral artery Femur Gene expression Glycerophosphate Heart diseases Kidney diseases Mitochondria Muscles Nodules Oxidative stress Reactive oxygen species Reduction siRNA Smooth muscle Superoxide dismutase |
| title | Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α Inhibits Vascular Calcification Through Sirtuin 3-Mediated Reduction of Mitochondrial Oxidative Stress |
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