Bone Morphogenic Protein 4-Smad–Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function
OBJECTIVE—Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The presen...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2016-03, Vol.36 (3), p.553-560 |
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| container_title | Arteriosclerosis, thrombosis, and vascular biology |
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| creator | Hu, Weining Zhang, Yang Wang, Li Lau, Chi Wai Xu, Jian Luo, Jiang-Yun Gou, Lingshan Yao, Xiaoqiang Chen, Zhen-Yu Ma, Ronald Ching Wan Tian, Xiao Yu Huang, Yu |
| description | OBJECTIVE—Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus.
APPROACH AND RESULTS—We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα.
CONCLUSIONS—The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice. |
| doi_str_mv | 10.1161/ATVBAHA.115.306302 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1768560481</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1768560481</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5302-bd790225c943132fd21c2db70845c9715d0b5dbbd7b6add450587b89218a54403</originalsourceid><addsrcrecordid>eNp9kM1O3DAUhS0EKpT2BVhUXrIJtR3bSZbhZ2AkKpCAbiPHvkNSnDi1HYbu-g59wz5JjWboktU99-o7R7oHoSNKTiiV9Gt9__20vqrTIk5yInPCdtABFYxnXOZyN2lSVJmQnO2jjyH8IIRwxsgHtM9kISvC5QF6OXUj4G_OT517hLHX-Na7CP2IeXY3KPP395_laGYNBj9MHh5nq2LvRuxW-DZJsBCzc_D9cwIuvVvHDi-Ujs7jusbLYVK9D_hiNC52YHtl8WIe9WvCJ7S3UjbA5-08RA-Li_uzq-z65nJ5Vl9nWqSHstYUFWFM6IrnNGcrw6hmpi1IydOtoMKQVpg2Ya1UxnBBRFm0ZcVoqQTnJD9Ex5vcybufM4TYDH3QYK0awc2hoYUshSS8pAllG1R7F4KHVTP5flD-V0NJ89p4s208LaLZNJ5MX7b5czuA-W95qzgBcgOsnY3gw5Od1-CbDpSN3XvJ_wCnYY56</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1768560481</pqid></control><display><type>article</type><title>Bone Morphogenic Protein 4-Smad–Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><source>Alma/SFX Local Collection</source><creator>Hu, Weining ; Zhang, Yang ; Wang, Li ; Lau, Chi Wai ; Xu, Jian ; Luo, Jiang-Yun ; Gou, Lingshan ; Yao, Xiaoqiang ; Chen, Zhen-Yu ; Ma, Ronald Ching Wan ; Tian, Xiao Yu ; Huang, Yu</creator><creatorcontrib>Hu, Weining ; Zhang, Yang ; Wang, Li ; Lau, Chi Wai ; Xu, Jian ; Luo, Jiang-Yun ; Gou, Lingshan ; Yao, Xiaoqiang ; Chen, Zhen-Yu ; Ma, Ronald Ching Wan ; Tian, Xiao Yu ; Huang, Yu</creatorcontrib><description>OBJECTIVE—Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus.
APPROACH AND RESULTS—We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα.
CONCLUSIONS—The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.115.306302</identifier><identifier>PMID: 26769046</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Adult ; Aged ; Animals ; Antibodies, Neutralizing - pharmacology ; Bone Morphogenetic Protein 4 - genetics ; Bone Morphogenetic Protein 4 - metabolism ; Bone Morphogenetic Protein 4 - pharmacology ; Case-Control Studies ; Cells, Cultured ; Diabetes Mellitus - metabolism ; Diabetes Mellitus - physiopathology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Endothelial Cells - drug effects ; Endothelial Cells - metabolism ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - physiopathology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Platelet-Derived Growth Factor - antagonists & inhibitors ; Platelet-Derived Growth Factor - metabolism ; Platelet-Derived Growth Factor - pharmacology ; Receptor, Platelet-Derived Growth Factor alpha - genetics ; Receptor, Platelet-Derived Growth Factor alpha - metabolism ; RNA Interference ; Signal Transduction - drug effects ; Smad Proteins, Receptor-Regulated - genetics ; Smad Proteins, Receptor-Regulated - metabolism ; Time Factors ; Tissue Culture Techniques ; Transfection ; Up-Regulation ; Vasodilation - drug effects ; Vasodilator Agents - pharmacology</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2016-03, Vol.36 (3), p.553-560</ispartof><rights>2016 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5302-bd790225c943132fd21c2db70845c9715d0b5dbbd7b6add450587b89218a54403</citedby><cites>FETCH-LOGICAL-c5302-bd790225c943132fd21c2db70845c9715d0b5dbbd7b6add450587b89218a54403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26769046$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Weining</creatorcontrib><creatorcontrib>Zhang, Yang</creatorcontrib><creatorcontrib>Wang, Li</creatorcontrib><creatorcontrib>Lau, Chi Wai</creatorcontrib><creatorcontrib>Xu, Jian</creatorcontrib><creatorcontrib>Luo, Jiang-Yun</creatorcontrib><creatorcontrib>Gou, Lingshan</creatorcontrib><creatorcontrib>Yao, Xiaoqiang</creatorcontrib><creatorcontrib>Chen, Zhen-Yu</creatorcontrib><creatorcontrib>Ma, Ronald Ching Wan</creatorcontrib><creatorcontrib>Tian, Xiao Yu</creatorcontrib><creatorcontrib>Huang, Yu</creatorcontrib><title>Bone Morphogenic Protein 4-Smad–Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus.
APPROACH AND RESULTS—We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα.
CONCLUSIONS—The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice.</description><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Antibodies, Neutralizing - pharmacology</subject><subject>Bone Morphogenetic Protein 4 - genetics</subject><subject>Bone Morphogenetic Protein 4 - metabolism</subject><subject>Bone Morphogenetic Protein 4 - pharmacology</subject><subject>Case-Control Studies</subject><subject>Cells, Cultured</subject><subject>Diabetes Mellitus - metabolism</subject><subject>Diabetes Mellitus - physiopathology</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endothelial Cells - drug effects</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>Platelet-Derived Growth Factor - antagonists & inhibitors</subject><subject>Platelet-Derived Growth Factor - metabolism</subject><subject>Platelet-Derived Growth Factor - pharmacology</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - genetics</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - metabolism</subject><subject>RNA Interference</subject><subject>Signal Transduction - drug effects</subject><subject>Smad Proteins, Receptor-Regulated - genetics</subject><subject>Smad Proteins, Receptor-Regulated - metabolism</subject><subject>Time Factors</subject><subject>Tissue Culture Techniques</subject><subject>Transfection</subject><subject>Up-Regulation</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilator Agents - pharmacology</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1O3DAUhS0EKpT2BVhUXrIJtR3bSZbhZ2AkKpCAbiPHvkNSnDi1HYbu-g59wz5JjWboktU99-o7R7oHoSNKTiiV9Gt9__20vqrTIk5yInPCdtABFYxnXOZyN2lSVJmQnO2jjyH8IIRwxsgHtM9kISvC5QF6OXUj4G_OT517hLHX-Na7CP2IeXY3KPP395_laGYNBj9MHh5nq2LvRuxW-DZJsBCzc_D9cwIuvVvHDi-Ujs7jusbLYVK9D_hiNC52YHtl8WIe9WvCJ7S3UjbA5-08RA-Li_uzq-z65nJ5Vl9nWqSHstYUFWFM6IrnNGcrw6hmpi1IydOtoMKQVpg2Ya1UxnBBRFm0ZcVoqQTnJD9Ex5vcybufM4TYDH3QYK0awc2hoYUshSS8pAllG1R7F4KHVTP5flD-V0NJ89p4s208LaLZNJ5MX7b5czuA-W95qzgBcgOsnY3gw5Od1-CbDpSN3XvJ_wCnYY56</recordid><startdate>201603</startdate><enddate>201603</enddate><creator>Hu, Weining</creator><creator>Zhang, Yang</creator><creator>Wang, Li</creator><creator>Lau, Chi Wai</creator><creator>Xu, Jian</creator><creator>Luo, Jiang-Yun</creator><creator>Gou, Lingshan</creator><creator>Yao, Xiaoqiang</creator><creator>Chen, Zhen-Yu</creator><creator>Ma, Ronald Ching Wan</creator><creator>Tian, Xiao Yu</creator><creator>Huang, Yu</creator><general>American Heart Association, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201603</creationdate><title>Bone Morphogenic Protein 4-Smad–Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function</title><author>Hu, Weining ; Zhang, Yang ; Wang, Li ; Lau, Chi Wai ; Xu, Jian ; Luo, Jiang-Yun ; Gou, Lingshan ; Yao, Xiaoqiang ; Chen, Zhen-Yu ; Ma, Ronald Ching Wan ; Tian, Xiao Yu ; Huang, Yu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5302-bd790225c943132fd21c2db70845c9715d0b5dbbd7b6add450587b89218a54403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Antibodies, Neutralizing - pharmacology</topic><topic>Bone Morphogenetic Protein 4 - genetics</topic><topic>Bone Morphogenetic Protein 4 - metabolism</topic><topic>Bone Morphogenetic Protein 4 - pharmacology</topic><topic>Case-Control Studies</topic><topic>Cells, Cultured</topic><topic>Diabetes Mellitus - metabolism</topic><topic>Diabetes Mellitus - physiopathology</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Endothelial Cells - drug effects</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>Platelet-Derived Growth Factor - antagonists & inhibitors</topic><topic>Platelet-Derived Growth Factor - metabolism</topic><topic>Platelet-Derived Growth Factor - pharmacology</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - genetics</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - metabolism</topic><topic>RNA Interference</topic><topic>Signal Transduction - drug effects</topic><topic>Smad Proteins, Receptor-Regulated - genetics</topic><topic>Smad Proteins, Receptor-Regulated - metabolism</topic><topic>Time Factors</topic><topic>Tissue Culture Techniques</topic><topic>Transfection</topic><topic>Up-Regulation</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Weining</creatorcontrib><creatorcontrib>Zhang, Yang</creatorcontrib><creatorcontrib>Wang, Li</creatorcontrib><creatorcontrib>Lau, Chi Wai</creatorcontrib><creatorcontrib>Xu, Jian</creatorcontrib><creatorcontrib>Luo, Jiang-Yun</creatorcontrib><creatorcontrib>Gou, Lingshan</creatorcontrib><creatorcontrib>Yao, Xiaoqiang</creatorcontrib><creatorcontrib>Chen, Zhen-Yu</creatorcontrib><creatorcontrib>Ma, Ronald Ching Wan</creatorcontrib><creatorcontrib>Tian, Xiao Yu</creatorcontrib><creatorcontrib>Huang, Yu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Weining</au><au>Zhang, Yang</au><au>Wang, Li</au><au>Lau, Chi Wai</au><au>Xu, Jian</au><au>Luo, Jiang-Yun</au><au>Gou, Lingshan</au><au>Yao, Xiaoqiang</au><au>Chen, Zhen-Yu</au><au>Ma, Ronald Ching Wan</au><au>Tian, Xiao Yu</au><au>Huang, Yu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone Morphogenic Protein 4-Smad–Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2016-03</date><risdate>2016</risdate><volume>36</volume><issue>3</issue><spage>553</spage><epage>560</epage><pages>553-560</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><abstract>OBJECTIVE—Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus.
APPROACH AND RESULTS—We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα.
CONCLUSIONS—The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>26769046</pmid><doi>10.1161/ATVBAHA.115.306302</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2016-03, Vol.36 (3), p.553-560 |
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| subjects | Adult Aged Animals Antibodies, Neutralizing - pharmacology Bone Morphogenetic Protein 4 - genetics Bone Morphogenetic Protein 4 - metabolism Bone Morphogenetic Protein 4 - pharmacology Case-Control Studies Cells, Cultured Diabetes Mellitus - metabolism Diabetes Mellitus - physiopathology Disease Models, Animal Dose-Response Relationship, Drug Endothelial Cells - drug effects Endothelial Cells - metabolism Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Endothelium, Vascular - physiopathology Humans Male Mice Mice, Inbred C57BL Middle Aged Platelet-Derived Growth Factor - antagonists & inhibitors Platelet-Derived Growth Factor - metabolism Platelet-Derived Growth Factor - pharmacology Receptor, Platelet-Derived Growth Factor alpha - genetics Receptor, Platelet-Derived Growth Factor alpha - metabolism RNA Interference Signal Transduction - drug effects Smad Proteins, Receptor-Regulated - genetics Smad Proteins, Receptor-Regulated - metabolism Time Factors Tissue Culture Techniques Transfection Up-Regulation Vasodilation - drug effects Vasodilator Agents - pharmacology |
| title | Bone Morphogenic Protein 4-Smad–Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function |
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