Abstract:
:Disordered angiogenesis is implicated in pulmonary vascular remodeling secondary to congenital heart diseases (CHD). However, the underlying genes are not well delineated. We showed previously that an ovine model of CHD with increased pulmonary blood flow (PBF, Shunt) has an "angiogenesis burst" between 1 and 4 wk of age. Thus we hypothesized that the increased PBF elicited a proangiogenic gene expression profile before onset of vessel growth. To test this we utilized microarray analysis to identify genes that could be responsible for the angiogenic response. Total RNA was isolated from lungs of Shunt and control lambs at 3 days of age and hybridized to Affymetrix gene chips for microarray analyses (n = 8/group). Eighty-nine angiogenesis-related genes were found to be upregulated and 26 angiogenesis-related genes downregulated in Shunt compared with control lungs (cutting at 1.2-fold difference, P < 0.05). We then confirmed upregulation of proangiogenic genes FGF2, Angiopoietin2 (Angpt2), and Birc5 at mRNA and protein levels and upregulation of ccl2 at mRNA level in 3-day Shunt lungs. Furthermore, we found that pulmonary arterial endothelial cells (PAEC) isolated from fetal lambs exhibited increased expression of FGF2, Angpt2, Birc5, and ccl2 and enhanced angiogenesis when exposed to elevated shear stress (35 dyn/cm²) compared with cells exposed to more physiological shear stress (20 dyn/cm²). Finally, we demonstrated that blocking FGF2, Angpt2, Birc5, or ccl2 signaling with neutralizing antibodies or small interfering RNA (siRNA) significantly decreased the angiogenic response induced by shear stress. In conclusion, we have identified a "proangiogenic" gene expression profile in a lamb model of CHD with increased PBF that precedes onset of pulmonary vascular remodeling. Our data indicate that FGF2, Angpt2, Birc5, and ccl2 may play important roles in the angiogenic response.
journal_name
Physiol Genomicsjournal_title
Physiological genomicsauthors
Tian J,Fratz S,Hou Y,Lu Q,Görlach A,Hess J,Schreiber C,Datar SA,Oishi P,Nechtman J,Podolsky R,She JX,Fineman JR,Black SMdoi
10.1152/physiolgenomics.00135.2010subject
Has Abstractpub_date
2011-01-01 00:00:00pages
87-98issue
2eissn
1094-8341issn
1531-2267pii
physiolgenomics.00135.2010journal_volume
43pub_type
杂志文章abstract::Physiological, morphological, and transcriptional alterations elicited by ethynyl estradiol in the uteri of Sprague-Dawley rats and C57BL/6 mice were assessed using comparable study designs, microarray platforms, and analysis methods to identify conserved estrogen signaling networks. Comparative analysis identified 15...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00175.2005
更新日期:2005-11-17 00:00:00
abstract::Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that regulates the oxygen-dependent expression of a number of genes. This transcription factor may contribute to the abundant expression of many genes in renal medullary cells that function normally under hypoxic conditions. The present study was d...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.2001.6.3.159
更新日期:2001-08-28 00:00:00
abstract::Cultured shrimp are continuously exposed to variable environmental conditions that have been associated with stress and subsequent outbreaks of disease. To investigate the effect of environmental stress on Penaeus monodon gene expression, a 3,853 random cDNA microarray chip was generated with clones originating from s...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00068.2007
更新日期:2007-09-19 00:00:00
abstract::Hypoxia is an important ecological, evolutionary, and biomedical stressor. While physiological acclimatization of mammals to hypoxia is well studied, the variation in gene expression that underlies acclimatization is not well studied. We acclimatized inbred mice for 32 days to hypoxic conditions that simulated altitud...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00075.2009
更新日期:2010-05-01 00:00:00
abstract::We investigated the expression and function of serum response factor (SRF) in endothelial-mesenchymal transition (EndMT) in glomerular endothelial cells (GEnCs) of diabetic nephropathy (DN). The expression of SRF, endothelial markers (VE-cadherin, CD31), and mesenchymal markers (α-SMA, FSP-1, fibronectin) was examined...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00082.2016
更新日期:2016-10-01 00:00:00
abstract::Hypertension (HTN) is a prevalent condition with complex etiology and pathophysiology. Evidence exists of significant communication between the nervous system and the immune system (IS), and there appears to be a direct role for inflammatory bone marrow (BM) cells in the pathophysiology of hypertension. However, the m...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00039.2016
更新日期:2016-07-01 00:00:00
abstract::Although a great deal has been elucidated concerning the mechanisms regulating muscle differentiation, little is known about transcription factor-specific gene regulation. Our understanding of the genetic mechanisms regulating cell differentiation is quite limited. Much of what has been defined centers on regulatory s...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00149.2004
更新日期:2004-12-15 00:00:00
abstract::Current models in skeletal muscle biology do not fully account for the breadth, causes, and consequences of phenotypic variation among skeletal muscle groups. The muscle allotype concept arose to explain frank differences between limb, masticatory, and extraocular (EOM) muscles, but there is little understanding of th...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00222.2003
更新日期:2004-07-08 00:00:00
abstract::MicroRNAs (miRs) are small, noncoding RNAs that are emerging as crucial regulators of cardiac remodeling in left ventricular hypertrophy (LVH) and failure (LVF). However, there are no data on their role in right ventricular hypertrophy (RVH) and failure (RVF). This is a critical question given that the RV is uniquely ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00163.2011
更新日期:2012-05-01 00:00:00
abstract::Dynamic, epigenetic mechanisms can regulate macrophage phenotypes following exposure to different stimulating conditions and environments. However, temporal patterns of microRNAs (miRNAs or miRs) across multiple macrophage polarization phenotypes have not been defined. We determined miRNA expression in bone marrow-der...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00098.2015
更新日期:2016-05-01 00:00:00
abstract::Vasopressin is a peptide hormone that regulates renal water excretion in part through its actions on the collecting duct. The regulation occurs in part via control of transcription of genes coding for the water channels aquaporin-2 (Aqp2) and aquaporin-3 (Aqp3). To identify transcription factors expressed in collectin...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00148.2009
更新日期:2010-02-04 00:00:00
abstract::Teleost fish represent unique models to study the role of neuroestrogens because of the extremely high activity of brain aromatase (AroB; the product of cyp19a1b). Aromatase respectively converts androstenedione and testosterone to estrone and 17beta-estradiol (E2). Specific inhibition of aromatase activity by fadrozo...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00051.2009
更新日期:2009-08-07 00:00:00
abstract::Caloric restriction (CR) is an effective method for prevention of age-associated diseases as well as overweight and obesity; however, there is controversy regarding the effects of dieting regimens on behavior. In this study, we investigated two different dieting regimens: repeated fasting and refeeding (RFR) and daily...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00082.2009
更新日期:2009-11-06 00:00:00
abstract::Besides neuronal plasticity, the neurotrophin brain-derived neurotrophic factor (BDNF) is also important in vascular function. The BDNF has been associated with angiogenesis through its specific receptor tropomyosin-related kinase B (TrkB). Additionally, Val66Met polymorphism decreases activity-induced BDNF. Since BDN...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00086.2015
更新日期:2016-02-01 00:00:00
abstract::Mesodermal and epidermal precursor cells undergo phenotypic changes during differentiation to the smooth muscle cell (SMC) lineage that are relevant to pathophysiological processes in the adult. Molecular mechanisms that underlie lineage determination and terminal differentiation of this cell type have received much a...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00148.2004
更新日期:2004-11-17 00:00:00
abstract::The gut microbiome plays a critical role in the onset and progression of obesity and the metabolic syndrome. However, it is not well documented whether the cecal vs. the fecal microbiome is more relevant when assessing their contributions to these diseases. Here, we amplified the V4 region of the 16S rRNA gene from ce...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00110.2017
更新日期:2018-05-01 00:00:00
abstract::In recent years, it has become evident that the adult mammalian CNS contains a population of neural stem cells (NSCs) described as immature, undifferentiated, multipotent cells, that may be called upon for repair in neurodegenerative and demyelinating diseases. NSCs may give rise to oligodendrocyte progenitor cells (O...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00021.2002
更新日期:2003-08-15 00:00:00
abstract::In type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, the pathogenic destruction of the insulin-producing pancreatic beta-cells is under the control of and influenced by distinct subsets of T lymphocytes. To identify the critical genes expressed by autoimmune T cells, antigen presenting cells, and pan...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00173.2004
更新日期:2005-04-14 00:00:00
abstract::The full extent to which 1,25-dihydroxyvitamin D(3) affects gene expression in human intestinal epithelial cells is unknown. We used oligonucleotide arrays to catalog vitamin D-induced changes in gene expression in Caco-2 cells, a human colon carcinoma cell line. Five paired sets of Caco-2 cell cultures were subjected...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00002.2003
更新日期:2004-04-13 00:00:00
abstract::Stearoyl-CoA desaturases (SCDs) are key enzymes of fatty acid biosynthesis whose regulation underpins responses to dietary, thermal, and hormonal treatment. Although two isoforms are known to exist in the common carp and human and four in mouse, there is no coherent view on how this gene family evolved to generate fun...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.90266.2008
更新日期:2008-09-17 00:00:00
abstract::It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00130.2016
更新日期:2017-06-01 00:00:00
abstract::Intrinsic aerobic exercise capacity can influence many complex traits including obesity and aging. To study this connection we established two rat lines by divergent selection of untrained aerobic capacity. After 32 generations the high capacity runners (HCR) and low capacity runners (LCR) differed in endurance runnin...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00118.2015
更新日期:2016-11-01 00:00:00
abstract::This study analyzes the electrophysiological cause and behavioral consequence of dopaminergic cell loss in a knockin mouse strain bearing hypersensitive nicotinic alpha4-receptor subunits ("L9'S mice"). Adult brains of L9'S mice show moderate loss of substantia nigra dopaminergic neurons and of striatal dopaminergic i...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00012.2004
更新日期:2004-08-11 00:00:00
abstract::Although some single polymorphism analyses of the angiotensinogen (AGT) gene have been found to be associated with hypertension, the results are still inconsistent. The objectives of this study are to evaluate the association of the genotype and haplotype distributions of three single-nucleotide polymorphisms (SNPs) (...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00133.2003
更新日期:2004-04-13 00:00:00
abstract::Resiquimod is a compound belonging to the imidazoquinoline family of compounds known to signal through Toll-like receptor 7. Resiquimod treatment has been demonstrated to inhibit the development of allergen induced asthma in experimental models. The aim of the present study was to elucidate the molecular processes tha...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00057.2009
更新日期:2009-08-07 00:00:00
abstract::Gene expression was measured during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice (n = 185) were allotted to a 2 x 2 factorial experiment consisting of either nonobese (ICR-control) or obese (M16-selected) mice fed a 7% fat, purified diet containing either 1% linoleic acid (LA) or...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00244.2004
更新日期:2005-05-11 00:00:00
abstract::In the mouse model of permanent, middle cerebral artery occlusion, infarct volume varies widely across inbred strains but generally is inversely correlated with collateral vessel number. However, we also observed certain mouse strains that share similar collateral vessel anatomy but exhibit significantly different inf...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00063.2013
更新日期:2013-09-03 00:00:00
abstract::The human miR-29 family of microRNAs has three mature members, miR-29a, miR-29b, and miR-29c. miR-29s are encoded by two gene clusters. Binding sites for several transcriptional factors have been identified in the promoter regions of miR-29 genes. The miR-29 family members share a common seed region sequence and are p...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00141.2011
更新日期:2012-02-27 00:00:00
abstract::High cardiorespiratory fitness (CRF) is associated with a reduced risk of Type 2 diabetes mellitus (T2DM) and improved β-cell function; genetic factors also determine these risks. This cross-sectional study investigated whether CRF modifies the association of polygenic risk of T2DM with glucose metabolism in nondiabet...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00027.2014
更新日期:2014-07-15 00:00:00
abstract::Uncoupling protein 1 (UCP1) is the first UCP described. It belongs to the family of mitochondrial carrier proteins and is expressed mainly in brown adipose tissue. Recently, the family of the UCPs has rapidly been growing due to the successive cloning of UCP2, UCP3, UCP4, and UCP5, also called brain mitochondrial carr...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00012.2005
更新日期:2005-08-11 00:00:00