Transcriptional regulation of cardiac genes balance pro- and anti-hypertrophic mechanisms in hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy. HCM is often hereditary, but our knowledge of the mechanisms leading from mutation to phenotype is incomplete. The transcriptional expression patterns in the myocar - dium of HCM patients may contribute t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2012-06-01
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| Series: | Cardiogenetics |
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| Online Access: | http://www.pagepressjournals.org/index.php/cardiogen/article/view/273 |
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| author | Nina Gennebäck Gerhard Wikström Urban Hellman Jane-Lise Samuel Anders Waldenström Stellan Mörner |
| author_facet | Nina Gennebäck Gerhard Wikström Urban Hellman Jane-Lise Samuel Anders Waldenström Stellan Mörner |
| author_sort | Nina Gennebäck |
| collection | DOAJ |
| description | Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy. HCM is often hereditary, but our knowledge of the mechanisms leading from mutation to phenotype is incomplete. The transcriptional expression patterns in the myocar - dium of HCM patients may contribute to understanding the mechanisms that drive and stabilize the hypertrophy. Cardiac myectomies/biopsies from 8 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 5 controls were studied with whole genome Illumina microarray gene expression (detecting 18 189 mRNA). When comparing HOCM myocardium to controls, there was significant transcriptional down-regulation of the <em>MYH6</em>, <em>EGR1</em>, <em>APOB</em> and <em>FOS</em> genes, and significant transcriptional up-regulation of the <em>ACE2</em>, <em>JAK2</em>, <em>NPPA</em> (<em>ANP</em>), <em>APOA1</em> and <em>HDAC5</em> genes. The transcriptional regulation revealed both pro- and anti-hypertrophic mechanisms. The pro-hypertrophic response was explained by the transcriptional down-regulation of <em>MYH6</em>, indicating that the switch to the fetal gene program is maintained, and the transcriptional up-regulation of <em>JAK2</em> in the JAK-STAT pathway. The anti-hypertrophic response was seen as a transcriptional down-regulation of the immediate early genes (IEGs), <em>FOS</em> and <em>EGR1</em>, and a transcriptional up-regulation of <em>ACE2</em> and <em>HDAC5</em>. This can be interpreted as a transcriptional endogenous protection system in the heart of the HOCM patients, neither growing nor suppressing the already hypertrophic myocardium. |
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| issn | 2035-8253 2035-8148 |
| language | English |
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| publishDate | 2012-06-01 |
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| series | Cardiogenetics |
| spelling | doaj.art-5e267fa6896a4fd4b7363c66ee02c8b12022-12-21T23:17:16ZengMDPI AGCardiogenetics2035-82532035-81482012-06-0121e5e510.4081/cardiogenetics.2012.e5288Transcriptional regulation of cardiac genes balance pro- and anti-hypertrophic mechanisms in hypertrophic cardiomyopathyNina Gennebäck0Gerhard Wikström1Urban Hellman2Jane-Lise Samuel3Anders Waldenström4Stellan Mörner5Department of Public Health and Clinical Medicine/Medicine, Umea University, UmeaDepartment of Medical Sciences, Cardiology, Uppsala University, UppsalaDepartment of Public Health and Clinical Medicine/Medicine, Umea University, UmeaINSERM U 942, 41, Bd de la Chapelle, Paris, France, Hôpital Lariboisière ParisDepartment of Cardiology, Heart Centre, Umeå University Hospital and Department of Public Health and Clinical Medicine, Umeå University, UmeåDepartment of Cardiology, Heart Centre, Umeå University Hospital and Department of Public Health and Clinical Medicine, Umeå University, UmeåHypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy. HCM is often hereditary, but our knowledge of the mechanisms leading from mutation to phenotype is incomplete. The transcriptional expression patterns in the myocar - dium of HCM patients may contribute to understanding the mechanisms that drive and stabilize the hypertrophy. Cardiac myectomies/biopsies from 8 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 5 controls were studied with whole genome Illumina microarray gene expression (detecting 18 189 mRNA). When comparing HOCM myocardium to controls, there was significant transcriptional down-regulation of the <em>MYH6</em>, <em>EGR1</em>, <em>APOB</em> and <em>FOS</em> genes, and significant transcriptional up-regulation of the <em>ACE2</em>, <em>JAK2</em>, <em>NPPA</em> (<em>ANP</em>), <em>APOA1</em> and <em>HDAC5</em> genes. The transcriptional regulation revealed both pro- and anti-hypertrophic mechanisms. The pro-hypertrophic response was explained by the transcriptional down-regulation of <em>MYH6</em>, indicating that the switch to the fetal gene program is maintained, and the transcriptional up-regulation of <em>JAK2</em> in the JAK-STAT pathway. The anti-hypertrophic response was seen as a transcriptional down-regulation of the immediate early genes (IEGs), <em>FOS</em> and <em>EGR1</em>, and a transcriptional up-regulation of <em>ACE2</em> and <em>HDAC5</em>. This can be interpreted as a transcriptional endogenous protection system in the heart of the HOCM patients, neither growing nor suppressing the already hypertrophic myocardium.http://www.pagepressjournals.org/index.php/cardiogen/article/view/273hypertrophic cardiomyopathy, HCM, gene expression, microarray. |
| spellingShingle | Nina Gennebäck Gerhard Wikström Urban Hellman Jane-Lise Samuel Anders Waldenström Stellan Mörner Transcriptional regulation of cardiac genes balance pro- and anti-hypertrophic mechanisms in hypertrophic cardiomyopathy Cardiogenetics hypertrophic cardiomyopathy, HCM, gene expression, microarray. |
| title | Transcriptional regulation of cardiac genes balance pro- and anti-hypertrophic mechanisms in hypertrophic cardiomyopathy |
| title_full | Transcriptional regulation of cardiac genes balance pro- and anti-hypertrophic mechanisms in hypertrophic cardiomyopathy |
| title_fullStr | Transcriptional regulation of cardiac genes balance pro- and anti-hypertrophic mechanisms in hypertrophic cardiomyopathy |
| title_full_unstemmed | Transcriptional regulation of cardiac genes balance pro- and anti-hypertrophic mechanisms in hypertrophic cardiomyopathy |
| title_short | Transcriptional regulation of cardiac genes balance pro- and anti-hypertrophic mechanisms in hypertrophic cardiomyopathy |
| title_sort | transcriptional regulation of cardiac genes balance pro and anti hypertrophic mechanisms in hypertrophic cardiomyopathy |
| topic | hypertrophic cardiomyopathy, HCM, gene expression, microarray. |
| url | http://www.pagepressjournals.org/index.php/cardiogen/article/view/273 |
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