Alpha 2.0

» Articles » PMID: 28128285

Differentially Expressed Genes and Canonical Pathway Expression in Human Atherosclerotic Plaques - Tampere Vascular Study

Overview

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jan 28

PMID 28128285

Citations 26

Authors

Authors

Miska Sulkava

Emma Raitoharju

Mari Levula

Ilkka Seppala

Leo-Pekka Lyytikainen

Ari Mennander

Otso Jarvinen

Rainer Zeitlin

Juha-Pekka Salenius

Thomas Illig

Norman Klopp

Nina Mononen

Reijo Laaksonen

Mika Kahonen

Niku Oksala

Terho Lehtimaki

Affiliations

Affiliations

Soon will be listed here.

Abstract

Cardiovascular diseases due to atherosclerosis are the leading cause of death globally. We aimed to investigate the potentially altered gene and pathway expression in advanced peripheral atherosclerotic plaques in comparison to healthy control arteries. Gene expression analysis was performed (Illumina HumanHT-12 version 3 Expression BeadChip) for 68 advanced atherosclerotic plaques (15 aortic, 29 carotid and 24 femoral plaques) and 28 controls (left internal thoracic artery (LITA)) from Tampere Vascular Study. Dysregulation of individual genes was compared to healthy controls and between plaques from different arterial beds and Ingenuity pathway analysis was conducted on genes with a fold change (FC) > ±1.5 and false discovery rate (FDR) < 0.05. 787 genes were significantly differentially expressed in atherosclerotic plaques. The most up-regulated genes were osteopontin and multiple MMPs, and the most down-regulated were cell death-inducing DFFA-like effector C and A (CIDEC, CIDEA) and apolipoprotein D (FC > 20). 156 pathways were differentially expressed in atherosclerotic plaques, mostly inflammation-related, especially related with leukocyte trafficking and signaling. In artery specific plaque analysis 50.4% of canonical pathways and 41.2% GO terms differentially expressed were in common for all three arterial beds. Our results confirm the inflammatory nature of advanced atherosclerosis and show novel pathway differences between different arterial beds.

Citing Articles

Paired Transcriptomic Analyses of Atheromatous and Control Vessels Reveal Novel Autophagy and Immunoregulatory Genes in Peripheral Artery Disease.

Machiraju P, Srinivas R, Kannan R, George R, Heymans S, Mukhopadhyay R Cells. 2024; 13(15.

PMID: 39120300 PMC: 11312159. DOI: 10.3390/cells13151269.

Identification of key genes for atherosclerosis in different arterial beds.

Wu X, Pan X, Zhou Y, Pan J, Kang J, Yu J Sci Rep. 2024; 14(1):6543.

PMID: 38503760 PMC: 10951242. DOI: 10.1038/s41598-024-55575-8.

Identification of key pyroptosis-related genes and microimmune environment among peripheral arterial beds in atherosclerotic arteries.

Liu J, Zhang Z, Lv X, Xu M, Ni B, He B Sci Rep. 2024; 14(1):233.

PMID: 38167983 PMC: 10761966. DOI: 10.1038/s41598-023-50689-x.

Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques.

Diez Benavente E, Karnewar S, Buono M, Mili E, Hartman R, Kapteijn D Arterioscler Thromb Vasc Biol. 2023; 43(10):1836-1850.

PMID: 37589136 PMC: 10521798. DOI: 10.1161/ATVBAHA.123.319325.

Correlation between Coronary Artery Disease with Other Arterial Systems: Similar, Albeit Separate, Underlying Pathophysiologic Mechanisms.

Achim A, Peter O, Cocoi M, Serban A, Mot S, Dadarlat-Pop A J Cardiovasc Dev Dis. 2023; 10(5).

PMID: 37233177 PMC: 10219089. DOI: 10.3390/jcdd10050210.

References

1.

Niessner A, Weyand C . Dendritic cells in atherosclerotic disease. Clin Immunol. 2009; 134(1):25-32. PMC: 2821659. DOI: 10.1016/j.clim.2009.05.006. View

2.

Galis Z, Khatri J . Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res. 2002; 90(3):251-62. View

3.

Turpeinen H, Seppala I, Lyytikainen L, Raitoharju E, Hutri-Kahonen N, Levula M . A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure. Hum Genet. 2015; 134(6):627-36. DOI: 10.1007/s00439-015-1546-5. View

4.

Leuschner F, Dutta P, Gorbatov R, Novobrantseva T, Donahoe J, Courties G . Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotechnol. 2011; 29(11):1005-10. PMC: 3212614. DOI: 10.1038/nbt.1989. View

5.

Ikeda T, Shirasawa T, Esaki Y, Yoshiki S, Hirokawa K . Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human atherosclerotic lesions of the aorta. J Clin Invest. 1993; 92(6):2814-20. PMC: 288482. DOI: 10.1172/JCI116901. View

6.

Conde L, Bevan S, Sitzer M, Klopp N, Illig T, Thiery J . Novel associations for coronary artery disease derived from genome wide association studies are not associated with increased carotid intima-media thickness, suggesting they do not act via early atherosclerosis or vessel remodeling. Atherosclerosis. 2011; 219(2):684-9. DOI: 10.1016/j.atherosclerosis.2011.08.031. View

7.

Tuomisto T, Korkeela A, Rutanen J, Viita H, Brasen J, Riekkinen M . Gene expression in macrophage-rich inflammatory cell infiltrates in human atherosclerotic lesions as studied by laser microdissection and DNA array: overexpression of HMG-CoA reductase, colony stimulating factor receptors, CD11A/CD18 integrins, and.... Arterioscler Thromb Vasc Biol. 2003; 23(12):2235-40. DOI: 10.1161/01.ATV.0000102551.91154.96. View

8.

Schunkert H, Konig I, Kathiresan S, Reilly M, Assimes T, Holm H . Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011; 43(4):333-8. PMC: 3119261. DOI: 10.1038/ng.784. View

9.

Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z . GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009; 10:48. PMC: 2644678. DOI: 10.1186/1471-2105-10-48. View

10.

von Essen M, Rahikainen R, Oksala N, Raitoharju E, Seppala I, Mennander A . Talin and vinculin are downregulated in atherosclerotic plaque; Tampere Vascular Study. Atherosclerosis. 2016; 255:43-53. DOI: 10.1016/j.atherosclerosis.2016.10.031. View

11.

Williams K, Tabas I . The response-to-retention hypothesis of early atherogenesis. Arterioscler Thromb Vasc Biol. 1995; 15(5):551-61. PMC: 2924812. DOI: 10.1161/01.atv.15.5.551. View

12.

Oksala N, Parssinen J, Seppala I, Raitoharju E, Kholova I, Ivana K . Association of neuroimmune guidance cue netrin-1 and its chemorepulsive receptor UNC5B with atherosclerotic plaque expression signatures and stability in human(s): Tampere Vascular Study (TVS). Circ Cardiovasc Genet. 2013; 6(6):579-87. DOI: 10.1161/CIRCGENETICS.113.000141. View

13.

Zhou J, Li Y, Chien S . Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler Thromb Vasc Biol. 2014; 34(10):2191-8. PMC: 4169328. DOI: 10.1161/ATVBAHA.114.303422. View

14.

Lund S, Giachelli C, Scatena M . The role of osteopontin in inflammatory processes. J Cell Commun Signal. 2009; 3(3-4):311-22. PMC: 2778587. DOI: 10.1007/s12079-009-0068-0. View

15.

Ramsey S, Vengrenyuk Y, Menon P, Podolsky I, Feig J, Aderem A . Epigenome-guided analysis of the transcriptome of plaque macrophages during atherosclerosis regression reveals activation of the Wnt signaling pathway. PLoS Genet. 2014; 10(12):e1004828. PMC: 4256277. DOI: 10.1371/journal.pgen.1004828. View

16.

Sajja L, Mannam G . Internal thoracic artery: anatomical and biological characteristics revisited. Asian Cardiovasc Thorac Ann. 2014; 23(1):88-99. DOI: 10.1177/0218492314523629. View

17.

Martins I, Hone E, Foster J, Sunram-Lea S, Gnjec A, Fuller S . Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease. Mol Psychiatry. 2006; 11(8):721-36. DOI: 10.1038/sj.mp.4001854. View

18.

STARY H . Changes in components and structure of atherosclerotic lesions developing from childhood to middle age in coronary arteries. Basic Res Cardiol. 1994; 89 Suppl 1:17-32. DOI: 10.1007/978-3-642-85660-0_2. View

19.

Wang J, Wei B, Cao S, Xu F, Chen W, Lin H . Identification by microarray technology of key genes involved in the progression of carotid atherosclerotic plaque. Genes Genet Syst. 2015; 89(6):253-8. DOI: 10.1266/ggs.89.253. View

20.

Perisic L, Aldi S, Sun Y, Folkersen L, Razuvaev A, Roy J . Gene expression signatures, pathways and networks in carotid atherosclerosis. J Intern Med. 2015; 279(3):293-308. DOI: 10.1111/joim.12448. View