TY - JOUR
T1 - Atherosclerosis pathways are activated in pericoronary adipose tissue of patients with coronary artery disease
AU - Konwerski, Michał
AU - Gromadka, Agnieszka
AU - Arendarczyk, Adam
AU - Koblowska, Marta
AU - Iwanicka-Nowicka, Roksana
AU - Wilimski, Radosław
AU - Czub, Paweł
AU - Filipiak, Krzysztof Jerzy
AU - Hendzel, Piotr
AU - Zielenkiewicz, Piotr
AU - Opolski, Grzegorz
AU - Gąsecka, Aleksandra
AU - Mazurek, Tomasz
N1 - Funding Information: The authors report no conflicts of interest in this work. This study was supported by the financial resources for maintaining research equipment and position grant (79/E-35/SPUB/SP/ 2019) of the Polish Ministry of Science and Higher Education. Publisher Copyright: © 2021 Konwerski et al.
PY - 2021
Y1 - 2021
N2 - Purpose: Perivascular release of inflammatory mediators may accelerate coronary lesion formation and contribute to plaque instability. Accordingly, we compared gene expression in pericoronary adipose tissue (PCAT) in patients with advanced coronary artery disease (CAD) and non-CAD controls. Patients and Methods: PCAT samples were collected during coronary bypass grafting from CAD patients (n = 21) and controls undergoing valve replacement surgery, with CAD excluded by coronary angiography (n = 19). Gene expression was measured by GeneChip™ Human Transcriptome Array 2.0. Obtained list of 1348 transcripts (2.0%) that passed the filter criteria was further analyzed by Ingenuity Pathway Analysis software, identifying 735 unique differentially expressed genes (DEGs). Results: Among the CAD patients, 416 (30.9%) transcripts were upregulated, and 932 (69.1%) were downregulated, compared to controls. The top upregulated genes were involved in inflammation and atherosclerosis (chemokines, interleukin-6, selectin E and lowdensity lipoprotein cholesterol (LDL-C) receptor), whereas the downregulated genes were involved in cardiac ischaemia and remodelling, platelet function and mitochondrial function (miR-3671, miR-4524a, multimerin, biglycan, tissue factor pathway inhibitor (TFPI), glucuronidases, miR-548, collagen type I, III, IV). Among the top upstream regulators, we identified molecules that have proinflammatory and atherosclerotic features (High Mobility Group Box 2 (HMGB2), platelet-derived growth platelet (PDGF) and evolutionarily conserved signaling intermediate in Toll pathways (ESCIT)). The activated pathway related to DEGs consisted of molecules with well-established role in the pathogenesis of atherosclerosis (TFPI, plasminogen activator, plasminogen activator, urokinase receptor (PLAUR), thrombomodulin). Moreover, we showed that 22 of the altered genes form a proatherogenic network. Conclusion: Altered gene expression in PCAT of CAD patients, with genes upregulation and activation of pathway involved in inflammation and atherosclerosis, may be involved in CAD development and progression.
AB - Purpose: Perivascular release of inflammatory mediators may accelerate coronary lesion formation and contribute to plaque instability. Accordingly, we compared gene expression in pericoronary adipose tissue (PCAT) in patients with advanced coronary artery disease (CAD) and non-CAD controls. Patients and Methods: PCAT samples were collected during coronary bypass grafting from CAD patients (n = 21) and controls undergoing valve replacement surgery, with CAD excluded by coronary angiography (n = 19). Gene expression was measured by GeneChip™ Human Transcriptome Array 2.0. Obtained list of 1348 transcripts (2.0%) that passed the filter criteria was further analyzed by Ingenuity Pathway Analysis software, identifying 735 unique differentially expressed genes (DEGs). Results: Among the CAD patients, 416 (30.9%) transcripts were upregulated, and 932 (69.1%) were downregulated, compared to controls. The top upregulated genes were involved in inflammation and atherosclerosis (chemokines, interleukin-6, selectin E and lowdensity lipoprotein cholesterol (LDL-C) receptor), whereas the downregulated genes were involved in cardiac ischaemia and remodelling, platelet function and mitochondrial function (miR-3671, miR-4524a, multimerin, biglycan, tissue factor pathway inhibitor (TFPI), glucuronidases, miR-548, collagen type I, III, IV). Among the top upstream regulators, we identified molecules that have proinflammatory and atherosclerotic features (High Mobility Group Box 2 (HMGB2), platelet-derived growth platelet (PDGF) and evolutionarily conserved signaling intermediate in Toll pathways (ESCIT)). The activated pathway related to DEGs consisted of molecules with well-established role in the pathogenesis of atherosclerosis (TFPI, plasminogen activator, plasminogen activator, urokinase receptor (PLAUR), thrombomodulin). Moreover, we showed that 22 of the altered genes form a proatherogenic network. Conclusion: Altered gene expression in PCAT of CAD patients, with genes upregulation and activation of pathway involved in inflammation and atherosclerosis, may be involved in CAD development and progression.
KW - Adipose tissue
KW - Atherosclerosis
KW - Gene expression
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=85117895811&partnerID=8YFLogxK
U2 - https://doi.org/10.2147/JIR.S326769
DO - https://doi.org/10.2147/JIR.S326769
M3 - Article
C2 - 34707383
SN - 1178-7031
VL - 14
SP - 5419
EP - 5431
JO - Journal of Inflammation Research
JF - Journal of Inflammation Research
ER -