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About Our Reseach Focus
The Stellos Lab is located at the European Center for Angioscience of the Heidelberg University in Mannheim, Germany. Our research focuses on the regulatory role of RNA in vascular endothelial control of age- and metabolic dysfunction-related diseases. Specifically, we investigate how inflammatory, metabolic, and RNA-biological mechanisms drive vascular and multi-organ disease.
The accompanying figure [integration of the image follows; editor's note] illustrates how ageing, hypertension, dyslipidemia, obesity, Western diet, and (epi)genetic risk converge on endothelial inflammation and dysregulation of RNA editing and modification. These processes promote cardiometabolic, renal, pulmonary, oncologic, and neurodegenerative diseases. Our mission is to translate these mechanisms into improved diagnostics and therapeutic strategies for patients.
We focus on four major research areas:
1. RNA in Systems Biology and Medicine
We study how RNA editing and epitranscriptomic alterations regulate endothelial function, immune activation, and vascular remodeling. Using patient cohorts, advanced RNA biology, and human cellular models, we identify RNA signatures linked to disease progression and therapeutic response.
Selected publications:
1: Vlachogiannis NI, Polycarpou-Schwarz M, Avdi AP, Tual-Chalot S, Stellos K.Targeting RNA adenosine editing and modification enzymes for RNA therapeutics. Mol Ther. 2025 Sep 3;33(9):4044-4090. doi: 10.1016/j.ymthe.2025.05.021.
2: Sachse M, Stellos K. Unraveling the RNA code: a uridine RNA modification drives glycoRNA biogenesis. Signal Transduct Target Ther. 2024 Nov 27;9(1):334. doi: 10.1038/s41392-024-02056-z.
3: Gatsiou A, Tual-Chalot S, Napoli M, Ortega-Gomez A, Regen T, Badolia R, Cesarini V, Garcia-Gonzalez C, Chevre R, Ciliberti G, Silvestre-Roig C, Martini M, Hoffmann J, Hamouche R, Visker JR, Diakos N, Wietelmann A, Silvestris DA, Georgiopoulos G, Moshfegh A, Schneider A, Chen W, Guenther S, Backs J, Kwak S, Selzman CH, Stamatelopoulos K, Rose-John S, Trautwein C, Spyridopoulos I, Braun T, Waisman A, Gallo A, Drakos SG, Dimmeler S, Sperandio M, Soehnlein O, Stellos K. The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation. Immunity. 2023 May 9;56(5):979-997.e11. doi: 10.1016/j.immuni.2023.03.021.
4: Sachse M, Tual-Chalot S, Ciliberti G, Amponsah-Offeh M, Stamatelopoulos K, Gatsiou A, Stellos K. RNA-binding proteins in vascular inflammation and atherosclerosis. Atherosclerosis. 2023 Jun;374:55-73. doi: 10.1016/j.atherosclerosis.2023.01.008.
5: Gatsiou A, Stellos K. RNA modifications in cardiovascular health and disease. Nat Rev Cardiol. 2023 May;20(5):325-346. doi: 10.1038/s41569-022-00804-8.
6: Vlachogiannis NI, Tual-Chalot S, Zormpas E, Bonini F, Ntouros PA, Pappa M, Bournia VK, Tektonidou MG, Souliotis VL, Mavragani CP, Stamatelopoulos K, Gatsiou A, Sfikakis PP, Stellos K. Adenosine-to-inosine RNA editing contributes to type I interferon responses in systemic sclerosis. J Autoimmun. 2021 Dec;125:102755. doi: 10.1016/j.jaut.2021.102755.
7: Vlachogiannis NI, Sachse M, Georgiopoulos G, Zormpas E, Bampatsias D, Delialis D, Bonini F, Galyfos G, Sigala F, Stamatelopoulos K, Gatsiou A, Stellos K. Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. J Mol Cell Cardiol. 2021 Nov;160:111-120. doi: 10.1016/j.yjmcc.2021.07.005.
8: Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF, Jaé N, Rossbach O, Amrhein C, Sigala F, Boon RA, Fürtig B, Manavski Y, You X, Uchida S, Keller T, Boeckel JN, Franco-Cereceda A, Maegdefessel L, Chen W, Schwalbe H, Bindereif A, Eriksson P, Hedin U, Zeiher AM, Dimmeler S. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by
enabling HuR-mediated post-transcriptional regulation. Nat Med. 2016 Oct;22(10):1140-1150. doi: 10.1038/nm.4172. Epub 2016 Sep 5. PMID: 27595325.
2. Angiometabolic Medicine
Our group examines how metabolic dysfunction drives vascular inflammation and residual risk in diabetes, obesity, and atherosclerosis across large clinical cohorts.
The Angiometabolic Study is an ongoing, prospective two-cecohort from Greece and Germany that investigates howmetabolic syndrome traits and aging interact to drive subclinical and clinically overt vascular disease. Since inception the study has enrolled 2,150 participants (target ≥2,800) and already has follow-up data on 1,100 individuals (median 24 months).
At baseline and at every follow-up visit (yearly for the first two years, then every two years) investigators collect a rich expose panel encompassing plasma, serum and whole blood samples anthropometrics and ultrasound-based fat-layer measuremendetailed dietary, smoking and exercise questionnaires; and traditional cardiometabolic risk factors.
Outcomes are assessed in parallel at each visit. Vascular imaging quantifies atherosclerosis burden and progression in the carotid-femoral axis, carotid–femoral pulse-wave velocity, microvascureactivity, and office/24-hour ambulatory blood-pressure profile (including aortic BP, pulse-wave analysis and central PWV). Coronary artery calcifi cation scores and coronary CT atherosclerosis grading are captured when available, while clinical follow-up focuses on major adverse cardiac events. By integrating high-resolution vascular ultrasonography, advanced hemodynamic measurements and a comprehensiveexposome (metabolic parameters, IL-6, Aβ40 and othercirculating biomarkers), the Angiometabolic Study provides an unrivaled platform to identify metabolic and inflammatory signatures that predict residual cardiovascular risk.
Study Endpoints
Subclinical Vascular Disease
- Carotid–femoral atherosclerosis burden and plaqueprogression by high-resolution ultrasonography
- Carotid–femoral pulse-wave velocity (macrovascular stiffness)
- Microvascular function (reactive hyperaemia/venousocclusion plethysmography)
Hemodynamic Profiles
- Office and 24-hour ambulatory blood pressure, including aortic (central) BP
- Pulse-wave analysis and central PWV parameters
Vascular Imaging
- High-resolution ultrasonography of peripheral arteries
- Total coronary artery atherosclerosis burden and lesion characterization by CT angiography
- Coronary artery calcium (CAC) score
Clinical Outcomes
- Incident and recurrent ASCVD events (myocardial infarction, coronary revascularization, stroke, peripheral arterial events)
- Hospitalisation for heart failure and other major adverse cardiac events (MACE)
Selected publications:
1: Mavraganis G, Georgiopoulos G, Athanasopoulos S, Terentes-Printzios D, Zervas G, Konstantaki C, Koilakou ME, Giannakopoulou SP, Dimopoulou MA, Chrysochoou C, Tsioufis K, Pitsavos C, Liberopoulos E, Stellos K, Vlachopoulos C, Panagiotakos D, Stamatelopoulos K. Improving cardiovascular risk stratification through the derivation and validation of an elevated triglyceride-glucose index. Diabetes Obes Metab. 2025 Nov 3. doi: 10.1111/dom.70270. Epub ahead of print. PMID: 41178693.
2: Mastrangelo A, Robles-Vera I, Mañanes D, Galán M, Femenía-Muiña M, Redondo-Urzainqui A, Barrero-Rodríguez R, Papaioannou E, Amores-Iniesta J, Devesa A, Lobo-González M, Carreras A, Beck KR, Ivarsson S, Gummesson A, Georgiopoulos G, Rodrigo-Tapias M, Martínez-Cano S, Fernández-López I, Nuñez V, Ferrarini A, Inohara N, Stamatelopoulos K, Benguría A, Cibrian D, Sánchez-Madrid F, Alonso-Herranz V, Dopazo A, Barbas C, Vázquez J, López JA, González-Martín A, Nuñez G, Stellos K, Bergström G, Bäckhed F, Fuster V, Ibañez B, Sancho D. Imidazole propionate is a driver and therapeutic target in atherosclerosis. Nature. 2025 Sep;645(8079):254-261. doi: 10.1038/s41586-025-09263-w. Epub 2025 Jul 16. PMID: 40670786; PMCID: PMC12408353.
3: Mavraganis G, Georgiopoulos G, Zervas G, Aivalioti E, Delialis D, Petropoulos I, Rachiotis N, Konstantaki C, Moustou C, Dimopoulou MA, Sachse M, Tual-Chalot S, Sopova K, Psimmenou E, Stellos K, Stamatelopoulos K. Circulating amyloid beta 1-40 peptide as an associate of renal function decline. Eur J Clin Invest. 2025 May;55(5):e70006. doi: 10.1111/eci.70006. Epub 2025 Feb 24. PMID: 39989380; PMCID: PMC12011680.
4: Georgiopoulos G, Athanasopoulos S, Mavraganis G, Konstantaki C, Papaioannou M, Delialis D, Angelidakis L, Sachse M, Papoutsis D, Cavlan B, Tual-Chalot S, Zervas G, Sopova K, Mitrakou A, Stellos K, Stamatelopoulos K. Incremental Value of Blood-Based Markers of Liver Fibrosis in Cardiovascular Risk Stratification. J Clin Endocrinol Metab. 2025 Mar 17;110(4):1115-1127. doi:
10.1210/clinem/dgae619. PMID: 39257198; PMCID: PMC11913098.
3. ImmunoVascular Control of Health and Disease
Cardiometabolic diseases have common traits likeendothelial dysfunction, inflammation, and fibrosis.The molecular mechanisms involved in theirdevelopment are not well understood. Endothelialcells play a key role in the progression of thesediseases by interacting with immune cells. The lab aims to understand how endothelial cells controlimmune responses to metabolic stress. We investigate leukocyte–endothelium interactions, inflammatory mediators, and their contribution to acute and chronic vascular disease.
Selected publications:
1: Gatsiou A, Tual-Chalot S, Napoli M, Ortega-Gomez A, Regen T, Badolia R, Cesarini V, Garcia-Gonzalez C, Chevre R, Ciliberti G, Silvestre-Roig C, Martini M, Hoffmann J, Hamouche R, Visker JR, Diakos N, Wietelmann A, Silvestris DA, Georgiopoulos G, Moshfegh A, Schneider A, Chen W, Guenther S, Backs J, Kwak S, Selzman CH, Stamatelopoulos K, Rose-John S, Trautwein C, Spyridopoulos I, Braun T, Waisman A, Gallo A, Drakos SG, Dimmeler S, Sperandio M, Soehnlein O, Stellos K. The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation. Immunity. 2023 May 9;56(5):979-997.e11. doi: 10.1016/j.immuni.2023.03.021. Epub 2023 Apr 25. PMID: 37100060.
2: Maneta E, Aivalioti E, Tual-Chalot S, Emini Veseli B, Gatsiou A, Stamatelopoulos K, Stellos K. Endothelial dysfunction and immunothrombosis in sepsis. Front Immunol. 2023 Apr 4;14:1144229. doi: 10.3389/fimmu.2023.1144229. PMID: 37081895; PMCID: PMC10110956.
3: Sachse M, Tual-Chalot S, Ciliberti G, Amponsah-Offeh M, Stamatelopoulos K, Gatsiou A, Stellos K. RNA-binding proteins in vascular inflammation and atherosclerosis. Atherosclerosis. 2023 Jun;374:55-73. doi: 10.1016/j.atherosclerosis.2023.01.008. Epub 2023 Jan 17. PMID: 36759270.
4: Vlachogiannis NI, Sachse M, Georgiopoulos G, Zormpas E, Bampatsias D, Delialis D, Bonini F, Galyfos G, Sigala F, Stamatelopoulos K, Gatsiou A, Stellos K. Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. J Mol Cell Cardiol. 2021 Nov;160:111-120. doi: 10.1016/j.yjmcc.2021.07.005. Epub 2021 Jul 21. PMID: 34302813; PMCID: PMC8585018.
5: Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF, Jaé N, Rossbach O, Amrhein C, Sigala F, Boon RA, Fürtig B, Manavski Y, You X, Uchida S, Keller T, Boeckel JN, Franco-Cereceda A, Maegdefessel L, Chen W, Schwalbe H, Bindereif A, Eriksson P, Hedin U, Zeiher AM, Dimmeler S. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by
enabling HuR-mediated post-transcriptional regulation. Nat Med. 2016 Oct;22(10):1140-1150. doi: 10.1038/nm.4172. Epub 2016 Sep 5. PMID: 27595325.
4. Cardiovascular Ageing & Systemic Disease
We explore how ageing alters vascular homeostasis and promotes heart failure, kidney disease, pulmonary vascular disease, cancer progression, and dementia.
Selected publications:
1: Liberale L, Tual-Chalot S, Sedej S, Ministrini S, Georgiopoulos G, Grunewald M, Bäck M, Bochaton-Piallat ML, Boon RA, Ramos GC, de Winther MPJ, Drosatos K, Evans PC, Ferguson JF, Forslund-Startceva SK, Goettsch C, Giacca M, Haendeler J, Kallikourdis M, Ketelhuth DFJ, Koenen RR, Lacolley P, Lutgens E, Maffia P, Miwa S, Monaco C, Montecucco F, Norata GD, Osto E, Richardson GD, Riksen NP, Soehnlein O, Spyridopoulos I, Van Linthout S, Vilahur G, Wentzel JJ, Andrés V, Badimon L, Benetos A, Binder CJ, Brandes RP, Crea F, Furman D, Gorbunova V, Guzik TJ, Hill JA, Lüscher TF, Mittelbrunn M, Nencioni A, Netea MG, Passos JF, Stamatelopoulos KS, Tavernarakis N, Ungvari Z, Wu JC, Kirkland JL, Camici GG, Dimmeler S, Kroemer G, Abdellatif M, Stellos K. Roadmap for alleviating the manifestations of ageing in the cardiovascular system. Nat Rev Cardiol. 2025 Aug;22(8):577-605. doi: 10.1038/s41569-025-01130-5. Epub 2025 Feb 19. PMID: 39972009.
2: Aivalioti E, Georgiopoulos G, Tual-Chalot S, Bampatsias D, Delialis D, Sopova K, Drakos SG, Stellos K, Stamatelopoulos K. Amyloid-beta metabolism in age-related neurocardiovascular diseases. Eur Heart J. 2025 Jan 16;46(3):250-272. doi: 10.1093/eurheartj/ehae655. PMID: 39527015; PMCID: PMC11735085.
3: Stakos DA, Stamatelopoulos K, Bampatsias D, Sachse M, Zormpas E, Vlachogiannis NI, Tual-Chalot S, Stellos K. The Alzheimer's Disease Amyloid-Beta Hypothesis in Cardiovascular Aging and Disease: JACC Focus Seminar. J Am Coll Cardiol. 2020 Mar 3;75(8):952-967. doi: 10.1016/j.jacc.2019.12.033. PMID: 32130931; PMCID: PMC7042886.
3: Delialis D, Georgiopoulos G, Tual-Chalot S, Angelidakis L, Aivalioti E, Mavraganis G, Sopova K, Argyris A, Kostakou P, Konstantaki C, Papaioannou M, Tsilimigras D, Chatoupis K, Zacharoulis AA, Galyfos G, Sigala F, Stellos K, Stamatelopoulos K. Amyloid beta is associated with carotid wall echolucency and atherosclerotic plaque composition. Sci Rep. 2024 Jun 28;14(1):14944. doi:
10.1038/s41598-024-64906-8. PMID: 38942831; PMCID: PMC11213915.
4: Stamatelopoulos K, Pol CJ, Ayers C, Georgiopoulos G, Gatsiou A, Brilakis ES, Khera A, Drosatos K, de Lemos JA, Stellos K. Amyloid-Beta (1-40) Peptide and Subclinical Cardiovascular Disease. J Am Coll Cardiol. 2018 Aug 28;72(9):1060-1061. doi: 10.1016/j.jacc.2018.06.027. PMID: 30139434; PMCID:
PMC6467498.
5: Stamatelopoulos K, Mueller-Hennessen M, Georgiopoulos G, Sachse M, Boeddinghaus J, Sopova K, Gatsiou A, Amrhein C, Biener M, Vafaie M, Athanasouli F, Stakos D, Pateras K, Twerenbold R, Badertscher P, Nestelberger T, Dimmeler S, Katus HA, Zeiher AM, Mueller C, Giannitsis E, Stellos K. Amyloid-β (1-40) and Mortality in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: A Cohort Study. Ann Intern Med. 2018 Jun 19;168(12):855-865. doi: 10.7326/M17-1540. Epub 2018 May 22. PMID: 29799975.
6: Stamatelopoulos K, Sibbing D, Rallidis LS, Georgiopoulos G, Stakos D, Braun S, Gatsiou A, Sopova K, Kotakos C, Varounis C, Tellis CC, Kastritis E, Alevizaki M, Tselepis AD, Alexopoulos P, Laske C, Keller T, Kastrati A, Dimmeler S, Zeiher AM, Stellos K. Amyloid-beta (1-40) and the risk of death from cardiovascular causes in patients with coronary heart disease. J Am Coll Cardiol. 2015 Mar 10;65(9):904-16. doi: 10.1016/j.jacc.2014.12.035. PMID: 25744007.