John H Lillvis, Robert Erdman, Charles M Schworer, Alicia Golden, Kimberly Derr, Zoran Gatalica, Laura A Cox, Jianbin Shen, Richard S Vander Heide, Guy M Lenk, Leigh Hlavaty, Li Li, James R Elmore, David P Franklin, John L Gray, Robert P Garvin, David J Carey, Wayne D Lancaster, Gerard Tromp, Helena Kuivaniemi
{"title":"HOXA4沿主动脉的区域表达及其在人腹主动脉瘤中的潜在作用。","authors":"John H Lillvis, Robert Erdman, Charles M Schworer, Alicia Golden, Kimberly Derr, Zoran Gatalica, Laura A Cox, Jianbin Shen, Richard S Vander Heide, Guy M Lenk, Leigh Hlavaty, Li Li, James R Elmore, David P Franklin, John L Gray, Robert P Garvin, David J Carey, Wayne D Lancaster, Gerard Tromp, Helena Kuivaniemi","doi":"10.1186/1472-6793-11-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression.</p><p><strong>Results: </strong>We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007).</p><p><strong>Conclusions: </strong>Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.</p>","PeriodicalId":35905,"journal":{"name":"BMC Physiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2011-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6793-11-9","citationCount":"35","resultStr":"{\"title\":\"Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms.\",\"authors\":\"John H Lillvis, Robert Erdman, Charles M Schworer, Alicia Golden, Kimberly Derr, Zoran Gatalica, Laura A Cox, Jianbin Shen, Richard S Vander Heide, Guy M Lenk, Leigh Hlavaty, Li Li, James R Elmore, David P Franklin, John L Gray, Robert P Garvin, David J Carey, Wayne D Lancaster, Gerard Tromp, Helena Kuivaniemi\",\"doi\":\"10.1186/1472-6793-11-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression.</p><p><strong>Results: </strong>We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007).</p><p><strong>Conclusions: </strong>Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.</p>\",\"PeriodicalId\":35905,\"journal\":{\"name\":\"BMC Physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2011-05-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1186/1472-6793-11-9\",\"citationCount\":\"35\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Physiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/1472-6793-11-9\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Physiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/1472-6793-11-9","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms.
Background: The infrarenal abdominal aorta exhibits increased disease susceptibility relative to other aortic regions. Allograft studies exchanging thoracic and abdominal segments showed that regional susceptibility is maintained regardless of location, suggesting substantial roles for embryological origin, tissue composition and site-specific gene expression.
Results: We analyzed gene expression with microarrays in baboon aortas, and found that members of the HOX gene family exhibited spatial expression differences. HOXA4 was chosen for further study, since it had decreased expression in the abdominal compared to the thoracic aorta. Western blot analysis from 24 human aortas demonstrated significantly higher HOXA4 protein levels in thoracic compared to abdominal tissues (P < 0.001). Immunohistochemical staining for HOXA4 showed nuclear and perinuclear staining in endothelial and smooth muscle cells in aorta. The HOXA4 transcript levels were significantly decreased in human abdominal aortic aneurysms (AAAs) compared to age-matched non-aneurysmal controls (P < 0.00004). Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007).
Conclusions: Our results demonstrated spatial variation in expression of HOXA4 in human aortas that persisted into adulthood and that downregulation of HOXA4 expression was associated with AAAs, an important aortic disease of the ageing population.
BMC PhysiologyBiochemistry, Genetics and Molecular Biology-Physiology
CiteScore
9.60
自引率
0.00%
发文量
0
期刊介绍:
BMC Physiology is an open access journal publishing original peer-reviewed research articles in cellular, tissue-level, organismal, functional, and developmental aspects of physiological processes. BMC Physiology (ISSN 1472-6793) is indexed/tracked/covered by PubMed, MEDLINE, BIOSIS, CAS, EMBASE, Scopus, Zoological Record and Google Scholar.