Reduced ACTC1 Expression Might Play a Role in the Onset of Congenital Heart Disease by Inducing Cardiomyocyte Apoptosis
Background: The Cardiac α actin 1 gene (ACTC1) has been related to familial atrial septal defects. This study was set to explore a potential role of this gene in the formation of sporadic congenital heart disease (CHD). Methods and Results: Assessment of cardiac tissue samples from 33 patients with...
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| Veröffentlicht in: | Circulation Journal 2010, Vol.74(11), pp.2410-2418 |
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| creator | Jiang, Hong-Kun Qiu, Guang-Rong Li-Ling, Jesse Xin, Na Sun, Kai-Lai |
| description | Background: The Cardiac α actin 1 gene (ACTC1) has been related to familial atrial septal defects. This study was set to explore a potential role of this gene in the formation of sporadic congenital heart disease (CHD). Methods and Results: Assessment of cardiac tissue samples from 33 patients with sporadic CHD (gestational age (GA) 18 weeks-49 months) with real-time RT-PCR, Western blotting and immunohistochemistry has revealed a markedly decreased ACTC1 expression in the majority of samples (78.8%) compared with autopsied normal heart tissue from aged-matched subjects (GA 17 weeks-36 months). Also, as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, the proportion of apoptotic cardiomyocytes in samples featuring down-regulated ACTC1 expression (Group 1) was significantly greater than those with normal expression (Group 2) and the controls (P |
| doi_str_mv | 10.1253/circj.CJ-10-0234 |
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This study was set to explore a potential role of this gene in the formation of sporadic congenital heart disease (CHD). Methods and Results: Assessment of cardiac tissue samples from 33 patients with sporadic CHD (gestational age (GA) 18 weeks-49 months) with real-time RT-PCR, Western blotting and immunohistochemistry has revealed a markedly decreased ACTC1 expression in the majority of samples (78.8%) compared with autopsied normal heart tissue from aged-matched subjects (GA 17 weeks-36 months). Also, as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, the proportion of apoptotic cardiomyocytes in samples featuring down-regulated ACTC1 expression (Group 1) was significantly greater than those with normal expression (Group 2) and the controls (P<0.01). The proportion of apoptotic cells strongly correlated with the expression of ACTC1 (r=-0.918, P<0.01). A study of 2 essential genes involved in apoptosis, Caspase-3 and Bcl-2, confirmed that the former has significantly increased expression, whilst the latter has decreased expression in Group 1 than in the other groups (P<0.01). Transfection of a small interfering RNA targeting, Actc1 (Actc1-siRNA), to a cardiomyocyte cell line, H9C2, also detected more apoptotic cells. Conclusions: Reduced ACTC1 expression might play a role in the onset of CHD through induction of cardiomyocyte apoptosis. (Circ J 2010; 74: 2410-2418)</description><identifier>ISSN: 1346-9843</identifier><identifier>EISSN: 1347-4820</identifier><identifier>DOI: 10.1253/circj.CJ-10-0234</identifier><identifier>PMID: 20962418</identifier><language>eng</language><publisher>Japan: The Japanese Circulation Society</publisher><subject>Actins - genetics ; Actins - metabolism ; Age Factors ; Animals ; Apoptosis ; Bcl-2 ; Blotting, Western ; Cardiac α actin 1 ; Case-Control Studies ; Caspase 3 - genetics ; Caspase-3 ; Cell Line ; Child, Preschool ; China ; Congenital heart disease ; Down-Regulation ; Female ; Gene Expression Regulation, Developmental ; Gestational Age ; Heart Defects, Congenital - genetics ; Heart Defects, Congenital - metabolism ; Heart Defects, Congenital - pathology ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Infant ; Infant, Newborn ; Male ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - pathology ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; RNA Interference ; RNA, Messenger - metabolism ; Transfection</subject><ispartof>Circulation Journal, 2010, Vol.74(11), pp.2410-2418</ispartof><rights>2010 THE JAPANESE CIRCULATION SOCIETY</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c642t-d44468a4b056765f71f63774b50acb492418dd5d41be9b4b1795fb88613d798f3</citedby><cites>FETCH-LOGICAL-c642t-d44468a4b056765f71f63774b50acb492418dd5d41be9b4b1795fb88613d798f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20962418$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Hong-Kun</creatorcontrib><creatorcontrib>Qiu, Guang-Rong</creatorcontrib><creatorcontrib>Li-Ling, Jesse</creatorcontrib><creatorcontrib>Xin, Na</creatorcontrib><creatorcontrib>Sun, Kai-Lai</creatorcontrib><title>Reduced ACTC1 Expression Might Play a Role in the Onset of Congenital Heart Disease by Inducing Cardiomyocyte Apoptosis</title><title>Circulation Journal</title><addtitle>Circ J</addtitle><description>Background: The Cardiac α actin 1 gene (ACTC1) has been related to familial atrial septal defects. This study was set to explore a potential role of this gene in the formation of sporadic congenital heart disease (CHD). Methods and Results: Assessment of cardiac tissue samples from 33 patients with sporadic CHD (gestational age (GA) 18 weeks-49 months) with real-time RT-PCR, Western blotting and immunohistochemistry has revealed a markedly decreased ACTC1 expression in the majority of samples (78.8%) compared with autopsied normal heart tissue from aged-matched subjects (GA 17 weeks-36 months). Also, as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, the proportion of apoptotic cardiomyocytes in samples featuring down-regulated ACTC1 expression (Group 1) was significantly greater than those with normal expression (Group 2) and the controls (P<0.01). The proportion of apoptotic cells strongly correlated with the expression of ACTC1 (r=-0.918, P<0.01). A study of 2 essential genes involved in apoptosis, Caspase-3 and Bcl-2, confirmed that the former has significantly increased expression, whilst the latter has decreased expression in Group 1 than in the other groups (P<0.01). Transfection of a small interfering RNA targeting, Actc1 (Actc1-siRNA), to a cardiomyocyte cell line, H9C2, also detected more apoptotic cells. Conclusions: Reduced ACTC1 expression might play a role in the onset of CHD through induction of cardiomyocyte apoptosis. (Circ J 2010; 74: 2410-2418)</description><subject>Actins - genetics</subject><subject>Actins - metabolism</subject><subject>Age Factors</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Bcl-2</subject><subject>Blotting, Western</subject><subject>Cardiac α actin 1</subject><subject>Case-Control Studies</subject><subject>Caspase 3 - genetics</subject><subject>Caspase-3</subject><subject>Cell Line</subject><subject>Child, Preschool</subject><subject>China</subject><subject>Congenital heart disease</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gestational Age</subject><subject>Heart Defects, Congenital - genetics</subject><subject>Heart Defects, Congenital - metabolism</subject><subject>Heart Defects, Congenital - pathology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Male</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Rats</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA Interference</subject><subject>RNA, Messenger - metabolism</subject><subject>Transfection</subject><issn>1346-9843</issn><issn>1347-4820</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM9v2yAYQNG0ae2y3XeauO3kDmwM5hh5XX-oU6eqOyPAnxMiBzwg6vzfz26y9gIIve9J30PoMyUXtKyrb9ZFu7tobwtKClJW7A06pxUTBWtK8vb5zQvZsOoMfUhpR0gpSS3fo7OSSF4y2pyjpwfoDhY6vG4fW4ov_44RUnLB459us83416AnrPFDGAA7j_MW8L1PkHHocRv8BrzLesDXoGPG310CnQCbCd_4Wev8Brc6di7sp2CnDHg9hjGH5NJH9K7XQ4JPp3uFfv-4fGyvi7v7q5t2fVdYzspcdIwx3mhmSM0Fr3tBe14JwUxNtDVMLkt0Xd0xakAaZqiQdW-ahtOqE7LpqxX6evSOMfw5QMpq75KFYdAewiEpMXfgUsyNVogcSRtDShF6NUa313FSlKiltnqurdrb5WOpPY98OckPZg_dy8D_vDNwdQR2KesNvABzLGcHOBkFU5Qu56v6ldjqqMBX_wBtgZT8</recordid><startdate>2010</startdate><enddate>2010</enddate><creator>Jiang, Hong-Kun</creator><creator>Qiu, Guang-Rong</creator><creator>Li-Ling, Jesse</creator><creator>Xin, Na</creator><creator>Sun, Kai-Lai</creator><general>The Japanese Circulation Society</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>2010</creationdate><title>Reduced ACTC1 Expression Might Play a Role in the Onset of Congenital Heart Disease by Inducing Cardiomyocyte Apoptosis</title><author>Jiang, Hong-Kun ; Qiu, Guang-Rong ; Li-Ling, Jesse ; Xin, Na ; Sun, Kai-Lai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c642t-d44468a4b056765f71f63774b50acb492418dd5d41be9b4b1795fb88613d798f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Actins - genetics</topic><topic>Actins - metabolism</topic><topic>Age Factors</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Bcl-2</topic><topic>Blotting, Western</topic><topic>Cardiac α actin 1</topic><topic>Case-Control Studies</topic><topic>Caspase 3 - genetics</topic><topic>Caspase-3</topic><topic>Cell Line</topic><topic>Child, Preschool</topic><topic>China</topic><topic>Congenital heart disease</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gestational Age</topic><topic>Heart Defects, Congenital - genetics</topic><topic>Heart Defects, Congenital - metabolism</topic><topic>Heart Defects, Congenital - pathology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Male</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Rats</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA Interference</topic><topic>RNA, Messenger - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Hong-Kun</creatorcontrib><creatorcontrib>Qiu, Guang-Rong</creatorcontrib><creatorcontrib>Li-Ling, Jesse</creatorcontrib><creatorcontrib>Xin, Na</creatorcontrib><creatorcontrib>Sun, Kai-Lai</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>Circulation Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Hong-Kun</au><au>Qiu, Guang-Rong</au><au>Li-Ling, Jesse</au><au>Xin, Na</au><au>Sun, Kai-Lai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced ACTC1 Expression Might Play a Role in the Onset of Congenital Heart Disease by Inducing Cardiomyocyte Apoptosis</atitle><jtitle>Circulation Journal</jtitle><addtitle>Circ J</addtitle><date>2010</date><risdate>2010</risdate><volume>74</volume><issue>11</issue><spage>2410</spage><epage>2418</epage><pages>2410-2418</pages><issn>1346-9843</issn><eissn>1347-4820</eissn><abstract>Background: The Cardiac α actin 1 gene (ACTC1) has been related to familial atrial septal defects. This study was set to explore a potential role of this gene in the formation of sporadic congenital heart disease (CHD). Methods and Results: Assessment of cardiac tissue samples from 33 patients with sporadic CHD (gestational age (GA) 18 weeks-49 months) with real-time RT-PCR, Western blotting and immunohistochemistry has revealed a markedly decreased ACTC1 expression in the majority of samples (78.8%) compared with autopsied normal heart tissue from aged-matched subjects (GA 17 weeks-36 months). Also, as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, the proportion of apoptotic cardiomyocytes in samples featuring down-regulated ACTC1 expression (Group 1) was significantly greater than those with normal expression (Group 2) and the controls (P<0.01). The proportion of apoptotic cells strongly correlated with the expression of ACTC1 (r=-0.918, P<0.01). A study of 2 essential genes involved in apoptosis, Caspase-3 and Bcl-2, confirmed that the former has significantly increased expression, whilst the latter has decreased expression in Group 1 than in the other groups (P<0.01). Transfection of a small interfering RNA targeting, Actc1 (Actc1-siRNA), to a cardiomyocyte cell line, H9C2, also detected more apoptotic cells. Conclusions: Reduced ACTC1 expression might play a role in the onset of CHD through induction of cardiomyocyte apoptosis. (Circ J 2010; 74: 2410-2418)</abstract><cop>Japan</cop><pub>The Japanese Circulation Society</pub><pmid>20962418</pmid><doi>10.1253/circj.CJ-10-0234</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actins - genetics Actins - metabolism Age Factors Animals Apoptosis Bcl-2 Blotting, Western Cardiac α actin 1 Case-Control Studies Caspase 3 - genetics Caspase-3 Cell Line Child, Preschool China Congenital heart disease Down-Regulation Female Gene Expression Regulation, Developmental Gestational Age Heart Defects, Congenital - genetics Heart Defects, Congenital - metabolism Heart Defects, Congenital - pathology Humans Immunohistochemistry In Situ Nick-End Labeling Infant Infant, Newborn Male Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology Proto-Oncogene Proteins c-bcl-2 - genetics Rats Reverse Transcriptase Polymerase Chain Reaction RNA Interference RNA, Messenger - metabolism Transfection |
| title | Reduced ACTC1 Expression Might Play a Role in the Onset of Congenital Heart Disease by Inducing Cardiomyocyte Apoptosis |
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