Upregulation of collagens detected by gene array in a model of flow-induced pulmonary vascular remodeling.
We recently reported localized increased pulmonary arterial resistance, neointimal lesions, and medial thickening induced by aortopulmonary anastomosis in young pigs. This model was used to investigate changes in expression of genes potentially involved in pulmonary vascular remodeling employing a high throughput Atlas Human Cardiovascular Array carrying approximately 600 cardiovascular-related cDNA sequences. Data were confirmed by Northern analysis, Western blots, and histological examination. With the use of lower stringency conditions for hybridization, 56% of the 588 human genes on the array showed visible signal after autoradiography. Approximately 10% of the genes with visible hybridization were altered by shunt-induced high flow. Extracellular matrix and cell adhesion molecules were the most highly represented group of upregulated genes. To our knowledge, our data are the first to demonstrate flow-induced changes in gene expression using a combination of cross species cDNA arrays, homologous hybridization, immunospecific protein, and histology. Our observations expand the list of genes as putative candidates in pulmonary vascular remodeling and support the utility of cross-species microarray analysis in such applications.
Medhora
Meetha
M
Department of Medicine and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Bousamra
Michael
M
Zhu
Daling
D
Somberg
Lewis
L
Jacobs
Elizabeth R
ER
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003094:Collagen / Q000235:genetics*; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D015870:Gene Expression / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D015345:Oligonucleotide Probes; D011651:Pulmonary Artery / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D013314:Stress, Mechanical; D013552:Swine; D015854:Up-Regulation / Q000502:physiology
C439971:COL3A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D003094:Collagen