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Open AccessArticle
Paired Transcriptomic Analyses of Atheromatous and Control Vessels Reveal Novel Autophagy and Immunoregulatory Genes in Peripheral Artery Disease
by
Praveen Machiraju
Praveen Machiraju 1,2,
Rajesh Srinivas
Rajesh Srinivas 3,
Ramaraj Kannan
Ramaraj Kannan 1,
Robbie George
Robbie George 3,
Stephane Heymans
Stephane Heymans 2,4,
Rupak Mukhopadhyay
Rupak Mukhopadhyay 5,* and
Arkasubhra Ghosh
Arkasubhra Ghosh 1,*
1
GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India
2
Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands
3
Department of Vascular and Endovascular Surgery, Narayana Health, Bangalore 560099, India
4
Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, bus911, 3000 Leuven, Belgium
5
Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, India
*
Authors to whom correspondence should be addressed.
Cells 2024, 13(15), 1269; https://doi.org/10.3390/cells13151269 (registering DOI)
Submission received: 15 June 2024
/
Revised: 17 July 2024
/
Accepted: 26 July 2024
/
Published: 28 July 2024
Abstract
Peripheral artery disease (PAD), a significant health burden worldwide, affects lower extremities due to atherosclerosis in peripheral vessels. Although the mechanisms of PAD have been well studied, the molecular milieu of the plaques localized within peripheral arteries are not well understood. Thus, to identify PAD-lesion-specific gene expression profiles precluding genetic, environmental, and dietary biases, we studied the transcriptomic profile of nine plaque tissues normalized to non-plaque tissues from the same donors. A total of 296 upregulated genes, 274 downregulated genes, and 186 non-coding RNAs were identified. STAG1, SPCC3, FOXQ1, and E2F3 were key downregulated genes, and CD93 was the top upregulated gene. Autophagosome assembly, cellular response to UV, cytoskeletal organization, TCR signaling, and phosphatase activity were the key dysregulated pathways identified. Telomerase regulation and autophagy were identified as novel interacting pathways using network analysis. The plaque tissue was predominantly composed of immune cells and dedifferentiated cell populations indicated by cell-specific marker-imputed gene expression analysis. This study identifies novel genes, non-coding RNAs, associated regulatory pathways, and the cell composition of the plaque tissue in PAD patients. The autophagy and immunoregulatory genes may drive novel mechanisms, resulting in atheroma. These novel interacting networks and genes have potential for PAD-specific therapeutic applications.
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MDPI and ACS Style
Machiraju, P.; Srinivas, R.; Kannan, R.; George, R.; Heymans, S.; Mukhopadhyay, R.; Ghosh, A.
Paired Transcriptomic Analyses of Atheromatous and Control Vessels Reveal Novel Autophagy and Immunoregulatory Genes in Peripheral Artery Disease. Cells 2024, 13, 1269.
https://doi.org/10.3390/cells13151269
AMA Style
Machiraju P, Srinivas R, Kannan R, George R, Heymans S, Mukhopadhyay R, Ghosh A.
Paired Transcriptomic Analyses of Atheromatous and Control Vessels Reveal Novel Autophagy and Immunoregulatory Genes in Peripheral Artery Disease. Cells. 2024; 13(15):1269.
https://doi.org/10.3390/cells13151269
Chicago/Turabian Style
Machiraju, Praveen, Rajesh Srinivas, Ramaraj Kannan, Robbie George, Stephane Heymans, Rupak Mukhopadhyay, and Arkasubhra Ghosh.
2024. "Paired Transcriptomic Analyses of Atheromatous and Control Vessels Reveal Novel Autophagy and Immunoregulatory Genes in Peripheral Artery Disease" Cells 13, no. 15: 1269.
https://doi.org/10.3390/cells13151269
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