scholarly journals Delineating the angiogenic gene expression profile before pulmonary vascular remodeling in a lamb model of congenital heart disease

2011 ◽  
Vol 43 (2) ◽  
pp. 87-98 ◽  
Author(s):  
Jing Tian ◽  
Sohrab Fratz ◽  
Yali Hou ◽  
Qing Lu ◽  
Agnes Görlach ◽  
...  
Keyword(s):  
Gene Expression ◽  
Shear Stress ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Vascular Remodeling ◽  
Neutralizing Antibodies ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Pulmonary Vascular Remodeling ◽  
Angiogenic Response

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.

Gene Expression Profile in Persons Exposed to the WTC With and Without PTSD

2009 ◽  
Author(s):  
Rachel Yehuda ◽  
Julia Golier ◽  
Sandro Galea ◽  
Marcus Ising ◽  
Florian Holsborer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile

scholarly journals Gene expression profile in functioning and non-functioning nodules of autonomous multinodular goiter from an area of iodine deficiency: unexpected common characteristics between the two entities

2021 ◽  
Author(s):  
P. Agretti ◽  
G. De Marco ◽  
E. Ferrarini ◽  
C. Di Cosmo ◽  
L. Montanelli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Multinodular Goiter ◽  
Kinase Inhibitor ◽  
Wnt Signaling Pathway ◽  
Iodine Intake ◽  
Healthy Tissue ◽  
Specific Gene ◽  
Complement Components

Abstract Purpose Toxic multinodular goiter is a heterogeneous disease associated with hyperthyroidism frequently detected in areas with deficient iodine intake, and functioning and non-functioning nodules, characterized by increased proliferation but opposite functional activity, may coexist in the same gland. To understand the distinct molecular pathology of each entity present in the same gland, the gene expression profile was evaluated by using the Affymetrix technology. Methods Total RNA was extracted from nodular and healthy tissues of two patients and double-strand cDNA was synthesized. Biotinylated cRNA was obtained and, after chemical fragmentation, was hybridized on U133A and B arrays. Each array was stained and the acquired images were analyzed to obtain the expression levels of the transcripts. Both functioning and non-functioning nodules were compared versus healthy tissue of the corresponding patient. Results About 16% of genes were modulated in functioning nodules, while in non-functioning nodules only 9% of genes were modulated with respect to the healthy tissue. In functioning nodules of both patients and up-regulation of cyclin D1 and cyclin-dependent kinase inhibitor 1 was observed, suggesting the presence of a possible feedback control of proliferation. Complement components C1s, C7 and C3 were down-regulated in both types of nodules, suggesting a silencing of the innate immune response. Cellular fibronectin precursor was up-regulated in both functioning nodules suggesting a possible increase of endothelial cells. Finally, Frizzled-1 was down-regulated only in functioning nodules, suggesting a role of Wnt signaling pathway in the proliferation and differentiation of these tumors. None of the thyroid-specific gene was deregulated in microarray analysis. Conclusion In conclusion, the main finding from our data is a similar modulation for both kinds of nodules in genes possibly implicated in thyroid growth.

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