Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies

Dimitris Kardassis; Cécile Vindis; Camelia Sorina Stancu; Laura Toma; Anca Violeta Gafencu; Adriana Georgescu; Nicoleta Alexandru-Moise; Filippo Molica; Brenda R Kwak; Alexandrina Burlacu; Ignacio Fernando Hall; Elena Butoi; Paolo Magni; Junxi Wu; Susana Novella; Luke F Gamon; Michael J Davies; Andrea Caporali; Fernando de la Cuesta; Tijana Mitić

doi:10.1016/j.vph.2024.107452

Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies

Dimitris Kardassis^*, Cécile Vindis, Camelia Sorina Stancu, Laura Toma, Anca Violeta Gafencu, Adriana Georgescu, Nicoleta Alexandru-Moise, Filippo Molica, Brenda R Kwak, Alexandrina Burlacu, Ignacio Fernando Hall, Elena Butoi, Paolo Magni, Junxi Wu, Susana Novella, Luke F Gamon, Michael J Davies, Andrea Caporali, Fernando de la Cuesta, Tijana Mitić^*

^*Corresponding author for this work

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death. To decipher this complexity, various cell model systems have been developed. With recent advances in systems biology approaches and single or multi-omics methods researchers can elucidate specific cell types, molecules and signalling pathways contributing to certain stages of disease progression. Compared with animals, in vitro models are economical, easily adjusted for high-throughput work, offering mechanistic insights. Hereby, we review the latest work performed employing the cellular models of atherosclerosis to generate a variety of omics data. We summarize their outputs and the impact they had in the field. Challenges in the translatability of the omics data obtained from the cell models will be discussed along with future perspectives. [Abstract copyright: Copyright © 2024. Published by Elsevier Inc.]

Original language	English
Article number	107452
Journal	Vascular pharmacology
Volume	158
Early online date	10 Dec 2024
DOIs	https://doi.org/10.1016/j.vph.2024.107452
Publication status	Published - Mar 2025

Funding

This article is based upon work from COST Action AtheroNET, CA21153, supported by COST (European Cooperation in Science and Technology). Dimitris Kardassis is supported by the Hellenic Foundation for Research and Innovation (HFRI) Research Program “Funding Projects in Leading-Edge Sectors – RRFQ: Basic Research Financing (Horizontal support for all Sciences) grant No 15529 and MSCA Staff Exchanges program CardioSCOPE Grant No 101086397. Camelia Sorina Stancu is supported by the Romanian Academy, and Ministry of Research, Innovation, and Digitization, CNCS-UEFISCDI grant number: PN-III-P4-PCE-2021-0831. Laura Toma is supported by the Romanian Academy, and Ministry of Research, Innovation, and Digitization, CNCS-UEFISCDI, grant number PN-III-P2-2.1-PED-2021-1929. Anca Gafencu is supported by a grant of the Ministry of Research, Innovation and Digitization, CNCS - UEFISCDI, project number PN-III-P4-PCE-2021-1755, within PNCDI III. Adriana Georgescu and Nicoleta Alexandru-Moise are supported by the Romania’s National Recovery and Resilience Plan, “European Union - NextGenerationEU", PNRR-III-C9-2022-I8, CF 93/15.11.2022, Financing Contract no.760063/23.05.2023, and by the Romanian Academy. Brenda R. Kwak is supported by the Swiss National Science Foundation, grant numbers 310030_212291/1 and 310030_182573). Ignacio Fernando Hall is supported by a British Heart Foundation (BHF) individual fellowship award (FS/IPBSRF/22/27050). The work of Paolo Magni is supported in part by the European Union (CardioSCOPE 10108639 - HORIZON-MSCA-2021-SE-01-01 MSCA Staff Exchanges 2021, AtheroNET COST Action CA21153), the Italian Space Agency (ASI; N. 2023-7-HH.0 CUP F13C23000050005 MicroFunExpo) and the Italian Ministry of Health (project PNRR-MCNT2-2023-12377808, PNRR: M6/C2_CALL 2023). Junxi Wu is supported by UKRI MRC New Investigator Research Grant (NIRG) (Ref: MR/V029827/1). Susana Novella is supported by the Spanish Ministry of Science and Innovation (ISCIII) (PI19/01714; PI22/1083) co-financed by the European Regional Development Fund (ERDF) and by the Generalitat Valenciana (CIAICO 2021/211). Luke F. Gamon is supported by a HALRIC grant (20230616_PP01). Michael J. Davies is supported by the Novo Nordisk Foundation (Laureate grant NNF20SA0064214). Fernando de la Cuesta is supported by Programa de Atracción de Talento (Modalidad 1), Comunidad Autónoma de Madrid 2023-5AIND-28938 and Ministerio de Ciencia, e Innovación y Universidades y Fondo Europeo de Desarrollo Regional (PID2021-126274OB-I00; CNS2022-135368). Andrea Caporali and Tijana Mitić acknowledge the support of the British Heart Foundation (BHF) Project Grant (PG/22/10916). Tijana Mitić is supported by the University of Edinburgh and British Heart Foundation (BHF) Research Excellence Award REA3 (RE/18/5/34216).

Keywords

Two dimensional (2D) models
Atherosclerosis
Shear stress and circumferential stretch models
Omics technologies
Three-dimensional (3D) models

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Kardassis-etal-Unravelling-molecular-mechanisms-in-atherosclerosis-using-cellular-models-and-omics-technologiesAccepted author manuscript, 910 KBLicence: CC BY 4.0

https://www.research.ed.ac.uk/en/publications/unravelling-molecular-mechanisms-in-atherosclerosis-using-cellulaLicence: CC BY 4.0

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Kardassis, D., Vindis, C., Stancu, C. S., Toma, L., Gafencu, A. V., Georgescu, A., Alexandru-Moise, N., Molica, F., Kwak, B. R., Burlacu, A., Hall, I. F., Butoi, E., Magni, P., Wu, J., Novella, S., Gamon, L. F., Davies, M. J., Caporali, A., de la Cuesta, F., & Mitić, T. (2025). Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies. Vascular pharmacology, 158, Article 107452. https://doi.org/10.1016/j.vph.2024.107452

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title = "Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies",

abstract = "Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death. To decipher this complexity, various cell model systems have been developed. With recent advances in systems biology approaches and single or multi-omics methods researchers can elucidate specific cell types, molecules and signalling pathways contributing to certain stages of disease progression. Compared with animals, in vitro models are economical, easily adjusted for high-throughput work, offering mechanistic insights. Hereby, we review the latest work performed employing the cellular models of atherosclerosis to generate a variety of omics data. We summarize their outputs and the impact they had in the field. Challenges in the translatability of the omics data obtained from the cell models will be discussed along with future perspectives. [Abstract copyright: Copyright {\textcopyright} 2024. Published by Elsevier Inc.]",

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Kardassis, D, Vindis, C, Stancu, CS, Toma, L, Gafencu, AV, Georgescu, A, Alexandru-Moise, N, Molica, F, Kwak, BR, Burlacu, A, Hall, IF, Butoi, E, Magni, P, Wu, J, Novella, S, Gamon, LF, Davies, MJ, Caporali, A, de la Cuesta, F & Mitić, T 2025, 'Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies', Vascular pharmacology, vol. 158, 107452. https://doi.org/10.1016/j.vph.2024.107452

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AU - Kardassis, Dimitris

AU - Vindis, Cécile

AU - Stancu, Camelia Sorina

AU - Toma, Laura

AU - Gafencu, Anca Violeta

AU - Georgescu, Adriana

AU - Alexandru-Moise, Nicoleta

AU - Molica, Filippo

AU - Kwak, Brenda R

AU - Burlacu, Alexandrina

AU - Hall, Ignacio Fernando

AU - Butoi, Elena

AU - Magni, Paolo

AU - Wu, Junxi

AU - Novella, Susana

AU - Gamon, Luke F

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AU - de la Cuesta, Fernando

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N2 - Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death. To decipher this complexity, various cell model systems have been developed. With recent advances in systems biology approaches and single or multi-omics methods researchers can elucidate specific cell types, molecules and signalling pathways contributing to certain stages of disease progression. Compared with animals, in vitro models are economical, easily adjusted for high-throughput work, offering mechanistic insights. Hereby, we review the latest work performed employing the cellular models of atherosclerosis to generate a variety of omics data. We summarize their outputs and the impact they had in the field. Challenges in the translatability of the omics data obtained from the cell models will be discussed along with future perspectives. [Abstract copyright: Copyright © 2024. Published by Elsevier Inc.]

AB - Despite the discovery and prevalent clinical use of potent lipid-lowering therapies, including statins and PCSK9 inhibitors, cardiovascular diseases (CVD) caused by atherosclerosis remain a large unmet clinical need, accounting for frequent deaths worldwide. The pathogenesis of atherosclerosis is a complex process underlying the presence of modifiable and non-modifiable risk factors affecting several cell types including endothelial cells (ECs), monocytes/macrophages, smooth muscle cells (SMCs) and T cells. Heterogeneous composition of the plaque and its morphology could lead to rupture or erosion causing thrombosis, even a sudden death. To decipher this complexity, various cell model systems have been developed. With recent advances in systems biology approaches and single or multi-omics methods researchers can elucidate specific cell types, molecules and signalling pathways contributing to certain stages of disease progression. Compared with animals, in vitro models are economical, easily adjusted for high-throughput work, offering mechanistic insights. Hereby, we review the latest work performed employing the cellular models of atherosclerosis to generate a variety of omics data. We summarize their outputs and the impact they had in the field. Challenges in the translatability of the omics data obtained from the cell models will be discussed along with future perspectives. [Abstract copyright: Copyright © 2024. Published by Elsevier Inc.]

KW - Two dimensional (2D) models

KW - Atherosclerosis

KW - Shear stress and circumferential stretch models

KW - Omics technologies

KW - Three-dimensional (3D) models

U2 - 10.1016/j.vph.2024.107452

DO - 10.1016/j.vph.2024.107452

M3 - Article

C2 - 39667548

SN - 1537-1891

VL - 158

JO - Vascular pharmacology

JF - Vascular pharmacology

M1 - 107452

ER -

Unravelling molecular mechanisms in atherosclerosis using cellular models and omics technologies

Abstract

Funding

Keywords

UN SDGs

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