Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of death worldwide. Several risk factors including obesity, type II diabetes, non-alcoholic fatty liver disease (NAFLD) and dyslipidemia predispose to ASCVD by mechanisms that are not fully understood. Reliable genetic or non-genetic biomarkers are also needed in order to increase the value of current risk prediction algorithms. In our lab we are studying the genetic determinants of atherosclerosis using in vitro systems, animal models, virus-mediated gene transfer and omics technologies. Our mission is to understand better the pathogenesis of atherosclerosis and to use this new knowledge in order to identify novel biomarkers and drug targets for ASCVD.
More specifically, we are interested in:
- Understanding the molecular mechanisms by which high density lipoproteins (HDL) protect from ASCVD and how this atheroprotection is compromised by mutations in HDL genes or in chronic inflammatory diseases.
- The identification, though transcriptomics approaches, of key genes and non-coding RNAs in metabolic organs, such as the liver and adipose tissue that are differential expressed and play causal roles in the pathogenesis of ASCVD.
- Understanding the role of hepatic nuclear factors (hormone nuclear receptors, FOX factors, SREBPs) in the regulation of genes involved in cholesterol and triglyceride metabolism in the liver and their dysregulation in ASCVD and other pathological conditions such as non-alcoholic liver disease (NAFLD).
Our research is funded by the EU and the Ministries of Education and Development of Hellas.
Thymiakou E, Othman A, Hornemann T, Kardassis D. (2020) Defects in High Density Lipoprotein metabolism and hepatic steatosis in mice with liver-specific ablation of Hepatocyte Nuclear Factor 4A. Metabolism. 110:154307.
Nasias D, Evangelakos I, Nidris V, Vassou D, Tarasco E, Lutz TA, Kardassis D. (2019) Significant changes in hepatic transcriptome and circulating miRNAs are associated with diet-induced metabolic syndrome in apoE3L.CETP mice. J Cell Physiol. 234:20485-20500.
Theofilatos D, Fotakis P, Valanti E, Sanoudou D, Zannis V, Kardassis D. (2018) HDL-apoA-I induces the expression of angiopoietin like 4 (ANGPTL4) in endothelial cells via a PI3K/AKT/FOXO1 signaling pathway. Metabolism. 87:36-47.
Kanaki M, Tiniakou I, Thymiakou E, Kardassis D. (2017) Physical and functional interactions between nuclear receptor LXRα and the forkhead box transcription factor FOXA2 regulate the response of the human lipoprotein lipase gene to oxysterols in hepatic cells. Biochim Biophys Acta Gene Regul Mech. 1860:848-860.
Tiniakou I, Drakos E, Sinatkas V, Van Eck M, Zannis VI, Boumpas D, Verginis P, Kardassis D. (2015) High-density lipoprotein attenuates Th1 and th17 autoimmune responses by modulating dendritic cell maturation and function. J Immunol. 194:4676-4687.
Valanti EK, Dalakoura-Karagkouni K, Siasos G, Kardassis D, Eliopoulos AG, and Sanoudou D. (2021) Advances in biological therapies for dyslipidemias and atherosclerosis. Metabolism. 116:154461.
Nasias D, Dalakoura-Karagkouni K, Vassou D, Papagiannakis G, Papadaki A, and Kardassis D. (2020) Transcriptome analysis of the adipose tissue in a mouse model of metabolic syndrome identifies gene signatures related to disease pathogenesis. Genomics. 112(6):4053-4062.
Chroni A, Rallidis L, Vassou D, Gkolfinopoulou C, Papakosta P, Zervou MI, Goulielmos GN, Kiouri E, Pappa D, Eliopoulos E, and Kardassis D. (2020) Identification and characterization of a rare variant in apolipoprotein A-IV, p.(V336M), and evaluation of HDL functionality in a Greek cohort with extreme HDL cholesterol levels. Arch Biochem Biophys. 696:108655.
Tarasco E, Boyle CN, Pellegrini G, Arnold M, Steiner R, Hornemann T, Nasias D, Kardassis D, Whiting L, and Lutz TA. (2019) Body weight-dependent and independent improvement in lipid metabolism after Roux-en-Y gastric bypass in ApoE*3Leiden.CETP mice. Int J Obes (Lond). 43(12):2394-2406.
Jaeger, A., Saely, C.H., Muendlein, A., Evangelakos, I., Nasias, D., Charizopoulou, N., Kardassis, D., Drexel, H. and von Eckardstein, A. (2018) Circulating microRNAs -192 and -194 are associated with the presence and incidence of diabetes mellitus. Sci. Rep. 8(1):14274.
Livitsanou M, Vasilaki E, Stournaras C, and Kardassis D. (2018) Modulation of TGFβ/Smad signaling by the small GTPase RhoB. Cell Signal. 48:54-63.
Kanaki M, and Kardassis D. (2017) Regulation of the human lipoprotein lipase gene by the forkhead box transcription factor FOXA2/HNF-3β in hepatic cells. Biochim Biophys Acta. 1860(3):327-336.
Kanaki M, Tiniakou I, Thymiakou E, and Kardassis D. (2017) Physical and functional interactions between nuclear receptor LXRα and the forkhead box transcription factor FOXA2 regulate the response of the human lipoprotein lipase gene to oxysterols in hepatic cells. Biochim Biophys Acta. 1860(8):848-860.
Theofilatos D, Anestis A, Hashimoto K, and Kardassis D. (2016) Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor 4α. Biochem Biophys Res Commun. 469(3):573-9.
Carthy JM, Stöter M, Bellomo C, Vanlandewijck M, Heldin A, Morén A, Kardassis D, Gahman TC, Shiau AK, Bickle M, Zerial M, Heldin CH, and Moustakas A. (2016) Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation. Sci Rep. 6:29868.
Fotakis P, Kuivenhoven JA, Dafnis E, Kardassis D, and Zannis VI. (2015) The Effect of Natural LCAT Mutations on the Biogenesis of HDL. Biochemistry. 54(21):3348-59.
Gkouskou KK, Ioannou M, Pavlopoulos GA, Georgila K, Siganou A, Nikolaidis G, Kanellis DC, Moore S, Papadakis KA, Kardassis D, Iliopoulos I, McDyer FA, Drakos E, and Eliopoulos AG. (2015) Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis. Oncogene. 35(19):2496-505.
Gkolfinopoulou C, Stratikos E, Theofilatos D, Kardassis D, Voulgari PV, Drosos AA, and Chroni A. (2015) Impaired Antiatherogenic Functions of High-density Lipoprotein in Patients with Ankylosing Spondylitis. J Rheumatol. 42(9):1652-60.
Tiniakou I, Kanaki Z, Georgopoulos S, Chroni A, Van Eck M, Fotakis P, Zannis VI, and Kardassis D. (2015) Natural human apoA-I mutations L141RPisa and L159RFIN alter HDL structure and functionality and promote atherosclerosis development in mice. Atherosclerosis. 243(1):77-85.
Stavri S, Simionescu M, Kardassis D, and Gafencu AV. (2015) Krüppel-like factor 4 synergizes with CREB to increase the activity of apolipoprotein E gene promoter in macrophages. Biochem Biophys Res Commun. 468(1-2):66-72.
Roman C, Fuior EV, Trusca VG, Kardassis D, Simionescu M, and Gafencu AV. (2015) Thyroid hormones upregulate apolipoprotein E gene expression in astrocytes. Biochem Biophys Res Commun. 468(1-2):190-5.
Fotakis P, Vezeridis A, Dafnis I, Chroni A, Kardassis D, and Zannis VI. (2014) apoE3[K146N/R147W] acts as a dominant negative apoE form that prevents remnant clearance and inhibits the biogenesis of HDL. J Lipid Res. 55(7):1310-1323.
Thymiakou E, and Kardassis D. (2014) Novel mechanism of transcriptional repression of the human ATP binding cassette transporter A1 gene in hepatic cells by the winged helix/forkhead box transcription factor A2. Biochim Biophys Acta. 1839(6):526-36.
Kardassis D, Mosialou I, Kanaki M, Tiniakou I, and Thymiakou E. (2014) Metabolism of HDL and its regulation. Curr Med Chem. 21(25):2864-80.
Papadakis G, Tsortos A, Kordas A, Tiniakou I, Morou E, Vontas J, Kardassis D, and Gizeli E. (2013) Acoustic detection of DNA conformation in genetic assays combined with PCR. Sci Rep. 3:2033.
Dimopoulou DG, Zervou MI, Trachana M, Myrthianou E, Pratsidou-Gertsi P, Kardassis D, Garyfallos A, and Goulielmos GN. (2013) Investigation of juvenile idiopathic arthritis susceptibility loci: results from a Greek population. Hum Immunol. 74(9):1194-8.
Costet P, Ehrenborg E, Fisher R, Fielding B, Groen A, Kardassis D, Malle E, Mulder M, Niemeier A, Norata GD, Hansen AT, and Eckardstein Av. (2013) European lipoprotein club: report of the 35th ELC annual conference. Atherosclerosis. 226(2):510-6.
Fotakis P, Tiniakou I, Kateifides AK, Gkolfinopoulou C, Chroni A, Stratikos E, Zannis VI, and Kardassis D. (2013) Significance of the hydrophobic residues 225 to 230 of apoA-I for the biogenesis of HDL. J Lipid Res. 54(12):3293-302.
Fotakis P, Kateifides A, Gkolfinopoulou C, Georgiadou D, Beck M, Grundler K, Chroni A, Stratikos E, Kardassis D, and Zannis VI. (2013) Role of the hydrophobic and charged residues in the 218 to 226 region of apoA-I in the biogenesis of HDL. J Lipid Res. 54(12):3281-92.
Schou J, Frikke-Schmidt R, Kardassis D, Thymiakou E, Nordestgaard BG, Jensen G, Grande P, and Tybjærg-Hansen A. (2012) Genetic variation in ABCG1 and risk of myocardial infarction and ischemic heart disease. Arterioscler Thromb Vasc Biol. 32(2):506-15.
Papadimitriou E, Vasilaki E, Vorvis C, Iliopoulos D, Moustakas A, Kardassis D, and Stournaras C. (2012) Differential regulation of the two RhoA-specific GEF isoforms Net1/Net1A by TGF-β and miR-24: role in epithelial-to-mesenchymal transition. Oncogene. 31(23):2862-75.
Stagakis I, Bertsias G, Karvounaris S, Kavousanaki M, Virla D, Raptopoulou A, Kardassis D, Boumpas DT, and Sidiropoulos PI. (2012) Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Res Ther. 14(3):R141.
Ohnsorg PM, Rohrer L, Perisa D, Kateifides A, Chroni A, Kardassis D, Zannis VI, and von Eckardstein A. (2011) Carboxyl Terminus of Apolipoprotein A-I (ApoA-I) Is Necessary for the Transport of Lipid-free ApoA-I but Not Prelipidated ApoA-I Particles through Aortic Endothelial Cells. J Biol Chem. 286(10):7744-54
Trusca GV, Fuior EV, Florea IC, Kardassis D, Simionescu M, and Gafencu AV. (2011) Macrophage-specific upregulation of apolipoprotein E gene expression by STAT1 is achieved via long-range genomic interactions. J Biol Chem. 286(16):13891-904
Mosialou I, Krasagakis K, and Kardassis D. (2011) Opposite regulation of the human apolipoprotein M gene by oHepatocyte Nuclear Factor 1 and Jun transcription factors. J Biol Chem. 13;286(19):17259-69.
Stender S, Frikke-Schmidt R, Anestis A, Kardassis D, Sethi AA, Nordestgaard BG, and Tybjærg-Hansen A. (2011) Genetic variation in liver X receptor alpha and risk of ischemic vascular disease in the general population. Arterioscler Thromb Vasc Biol. 31(12):2990-6.
Kateifides AK, Gorshkova IN, Duka A, Chroni A, Kardassis D, and Zannis VI. (2011) Alteration of negatively charged residues in the 89 to 99 domain of apoA-I affects lipid homeostasis and maturation of HDL. J Lipid Res. 52(7):1363-72.
Haase CL, Frikke-Schmidt R, Nordestgaard BG, Kateifides AK, Kardassis D, Nielsen LB, Andersen CB, Køber L, Johnsen AH, Grande P, Zannis VI, and Tybjaerg-Hansen A. (2011) Mutation in APOA1 predicts increased risk of ischaemic heart disease and total mortality without low HDL cholesterol levels. J Intern Med. 270(2):136-46.
Vasilaki E, Papadimitriou E, Tajadura V, Ridley AJ, Stournaras C and Kardassis D. (2010) Transcriptional regulation of the small GTPase RhoB gene by TGFβ-induced signaling pathways. FASEB J. 24(3):891-905.
Mavridou S, Venihaki M, Rassouli O, Tsatsanis C, and Kardassis D. (2010) Feedback inhibition of human scavenger receptor class B type I gene expression by glucocorticoid in adrenal and ovarian cells. Endocrinology 151(7):3214-24.
Mosialou I, Zannis VI, and Kardassis D. (2010) Regulation of human apolipoprotein m gene expression by orphan and ligand-dependent nuclear receptors. J Biol Chem. 285(40):30719-30.
Kardassis D, Murphy C, Fotsis T, Moustakas A, and Stournaras C. (2009) Control of transforming growth factor beta signal transduction by small GTPases. FEBS J. 276(11):2947-65.
Vasilaki, E., Siderakis, M,. Papakosta, P., Skourti-Stathaki, K. Mavridou, S. and Kardassis, D. (2009) Novel regulation of Smad3 oligomerization and DNA binding by its linker domain. Biochemistry. 48(35):8366-78.
Drosatos K, Sanoudou D, Kypreos KE, Kardassis D and Zannis VI. (2007) A dominant negative form of the transcription factor c-Jun affects genes that have opposing effects on lipid homeostasis in mice. J Biol Chem. 282, 19556-64.
Thymiakou E, Zannis VI, and Kardassis D. (2007) Physical and functional interactions between liver X receptor/retinoid X receptor and Sp1 modulate the transcriptional induction of the human ATP binding cassette transporter A1 gene by oxysterols and retinoids. Biochemistry. 46, 11473-83.
Koutsodontis G, Vasilaki E, Chou WC, Papakosta, P. and Kardassis D. (2005) Physical and functional interactions between members of the tumour suppressor p53 and the Sp families of transcription factors: importance for the regulation of genes involved in cell-cycle arrest and apoptosis. Biochem J. 389, 443-55.
Prokova V, Mavridou S, Papakosta P. and Kardassis D. (2005) Characterization of a novel transcriptionally active domain in the transforming growth factor beta-regulated Smad3 protein. Nucleic Acids Res. 33, 3708-21.
Koutsodontis G, and Kardassis D. (2004) Inhibition of p53-mediated transcriptional responses by mithramycin A. Oncogene. 23, 9190-200.
Chou C, Prokova V, Shiraishi K, Valcourt U, Moustakas A, Hadzopoulou-Cladaras M, Zannis V, and Kardassis D. (2003) Smad proteins co-activate hepatocyte nuclear factor 4 by interacting with multiple domains and enhance hepatic gene transcription. Mol Biol Cell 14, 1279-1294.
Prokova V, Mosialos G, and Kardassis D. (2002) Inhibition of transforming growth factor β signaling and Smad-dependent activation of transcription by the latent membrane protein 1 of Epstein Barr Virus. J Biol Chem. 277(11):9342-50.
Koutsodontis G, Moustakas A, and Kardassis D. (2002) The Role of Sp1 Family Members, the Proximal GC-Rich Motifs, and the Upstream Enhancer Region in the Regulation of the Human Cell Cycle Inhibitor p21(WAF-1/Cip1) Gene Promoter. Biochemistry. 41(42):12771-12784.
Koutsodontis G, Tentes I, Papakosta P, Moustakas A, and Kardassis D. (2001) Sp1 plays a critical role in the transcriptional activation of the human cyclin-dependent kinase inhibitor p21(WAF1/Cip1) gene by the p53 tumor suppressor protein. J Biol Chem. 276(31):29116-25.
Kardassis D, Pardali, K, and Zannis, VI. (2000) SMAD proteins transactivate the human apoC-III promoter by interacting physically and functionally with Hepatocyte Nuclear Factor 4. J. Biol. Chem. 29;275(52):41405-14.
Moustakas A, and Kardassis D. (1998) Activation of the human p21/WAF1/Cip1 gene promoter in hepatic cells by interactions between Sp1 and Smad family members. Proc Natl Acad Sci U S A. 95(12):6733-8.