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• Lipid metabolism in health and disease: dysregulation of lipid metabolism in atherosclerosis, diabetes, metabolic syndrome and obesity, cellular and molecular biology of lipoproteins (Lp), transport of Lp across the vascular endothelium, interaction of Lp with the cells of the arterial wall, in vivo and in vitro modification of low density Lp (LDL), dysfunctional high density Lp (HDL), entero-hepatic metabolism of Lp, molecular biology of proteins involved in cellular cholesterol efflux, implication in atheroma formation..

• Cellular biology and biochemistry of blood vessels: heart and cardiac valves in pathological conditions, biochemical and biophysical modifications in atherogenesis, diabetes and obesity, experimental animal models of atherosclerosis and/or diabetes.

• Novel biomarkers for cardiovascular disease: dysfunctional Lp, oxidized lipids, Lp-associated enzymes, inflammatory mediators.

• Genetic and epigenetic mechanisms of atherosclerosis and/or diabetes: gene polymorphisms, functional analysis of RNA-related epigenetic markers (microRNAs, lncRNAs), identification and validation of specific microRNAs target genes, gene editing of lipid-related proteins to improve cardiovascular diseases.

• Pharmacologic attempts to arrest or reverse cardiovascular diseases: pleiotropic properties of anti-atherosclerotic drugs (statins, calcium channel blockers - amlodipine), biologically active natural compounds (probiotics, caffeic acid, ginger extract, blueberries extract).

PERSPECTIVES

The understanding of the molecular mechanisms revealed by our projects will help decipher the complexity of gene regulation and signaling mechanisms modulated by atherogenic lipids, highlight new biomarkers for cardiovascular diseases and identify new therapeutic molecules to improve the life of many people affected by atherosclerosis, diabetes, metabolic syndrome and obesity.

MAIN INTERNATIONAL COLLABORATIONS

• 2003-2007 APOA5 mechanisms in triglyceride metabolism - Prof. Jean-Charles Fruchart and Dr. Jamila Fruchart-Najib, Institute Pasteur of Lille and University of Lille 2, Lille, France (Fruchart-Najib J. et al., Biochem. Biophys. Res. Commun. 2004; Niculescu L. et al., Clin Chem Lab. Med. 2007).

• 2004-2005 The control of lipid metabolizing enzymes in hyperlipidemic hamsters- Prof. Kyriakos Kypreos, Pharmacology Laboratory, University of Patras Medical School, Patras, Greece.

• 2006 Determination of IRS1 and IGF1R gene polymorphisms in patients with cardiovascular diseases by using gene array and qPCR techniques - Prof. Danilo Norata, Department for Pharmacological Sciences, Milano University, Milan, Italy.

• 2006 Effects of glycated LDL on scavenger receptors from human smooth muscle cells - Prof. Lina Badimon, Cardiovascular Research Center CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

• 2008 Methods to evaluate the serum antioxidant potential- paraoxonase1 (PON1) activity - Dr. Hagai Tavori, Laboratory of Natural Medicinal Compounds, MIGAL Galilee Technology Center, Haifa, Israel.

• 2008-2011 HDL associated enzymes in cardiovascular disease - Prof. Matti Jauhiainen and Dr. Marius R. Robciuc, National Institute for Health and Welfare, Helsinki, Finland (Robciuc M. et al., Lipids Health Dis. 2010; Niculescu L., et al., Biochem. Biophys. Res. Commun. 2011).

• 2012 Immunodetection of molecules specific for lipid metabolism, in tissues or cultured cells, by confocal microscopy - Prof. Jorg Hereen, Department of Biochemistry and Molecular Cell Biology, University Medical Clinic Hamburg-Eppendorf, Hamburg, Germany.

• 2012 MiRNAs analysis techniques in biological samples - Prof. Christian Weber, Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians Universität, Munich, Germany.

• 2012-2015 Molecular interactions of oxidized lipoproteins with vascular endothelial cells - Prof. Shlomo Sasson, Hebrew University, Jerusalem, Israel (Stancu C. et al., Molec. Nutr. Food Res. 2015; Riahi Y., ..., Simionescu M., Sima A., ..., Sasson S., J. Cell. Mol. Med. 2015).

• 2014 Functional analysis and bioinformatics of microRNAs - Prof. Leon de Windt, Molecular Cardiology department, Cardiovascular Research Institute (CARIM), Maastricht University, Maastricht, The Netherlands (Niculescu L. et al., Molec. Biol. Rep. 2018).

• 2017-2019 Bioinformatic analysis of microarray microRNAs distribution in hyperlipidemic hamster tissues - Dr. Yvan Devaux, Cardiovascular Research Unit, Luxembourg Institute of Health, Luxembourg (COST Action CA17129 "Catalysing transcriptomics research in cardiovascular disease" 2018-2022, CardioRNA network, https://cardiorna.eu/).

MAIN NATIONAL COLLABORATIONS

• 2003-2005 Romanian Academy “F. Rainer” Institute of Antropology (Dr. Cristina Glavce).

• 2003-2010 National Institute for Diabetes, Nutrition and Metabolic Diseases „N. Paulescu” (Prof. Dr. Constantin Ionescu Târgoviste, Dr. Maria Vlădică).

• 2006-2008 University of Medicine and Pharmacy „Carol Davila” and Cardiology Clinic of University Emergency Hospital Floreasca (Prof. Dr. Maria Dorobanţu).

• 2006-2008 National Endocrinology Institute „C.I. Parhon” (Dr. Olga Ianăş).

• 2007-2010 University of Medicine and Pharmacy „Carol Davila” (Prof. Dr. Denisa Margină).

• 2006-2010 NationalInstitute for Food Chemistry (Dr. Floarea Serbancea).

• 2012-2016 University of Medicine and Pharmacy „Carol Davila” and Cardiology Clinic of University Emergency Hospital Elias (Prof. Dr. Doina R. Dimulescu).

• 2016-2019 Cardiovascular Clinic of the “Agrippa Ionescu” Emergency Hospital (Dr. Viorel Goleanu, Dr. Oriana Moraru).

INTERNATIONAL GRANTS

• 2001-2004 Grant FP5 ICA1-CT-2000-70020, Centre of Excellence of the European Community, Function and dysfunction of blood vessels: transcytosis in normal and pathological states, alterations in atherosclerosis and diabetes; their therapeutic control.

• 2002-2004 NATO SCIENCE PROGRAMME, Role of ApoE in Cholesterol and Triglycerides Homeostasis.

• 2005-2007 Grant FP6, SSA-EC 16873 Strengthening the European Research Area by Reinforcement of Romanian Research Competency in Genomics and Proteomics of Major Global Risk Diseases: Atherosclerosis, Diabetes and its Complications.

• 2008-2011 COST Action BM0602 (WG3, WG 4) Adipose Tissue: A Key Target for Prevention of the Metabolic Syndrome, European Community Funds.

• 2008-2012 POS-CCE 143/SMIS CSNR 2667 Extension and modernization of the research infrastructure in order to increase competitiveness in the field of cardiovascular diseases, diabetes and obesity (CARDIPPRO), European Community Funds.

• 2014-2015 POS-CCE ID-1877/SMIS-CSNR 49154 Structuration of a new compartment for cellular sorting and tissue cryo-preservation for research and therapeutic purposes (SORTIS), European Community Funds.

• 2018-2022 COST Action CA17129 "Catalyzing transcriptomics research in cardiovascular disease" (CardioRNA network), European Community Funds.

GRANTS AWARDED BY COMPETITION (2001- 2019)

Studies in patients with cardiovascular diseases and/or diabetes

a. Cellular and molecular mechanisms of dyslipidemia

• 2003-2005 VIASAN PNCDI Grant, partners: National Institute for Diabetes, Nutrition and Metabolic Diseases „N. Paulescu” and Anthropology Institute „Fr. Rainer”, The impact of obesity in generating diabetes and cardiovascular diseases in urban communities from Romania - a population, physio-pathologic and genetic study (OBEDIAGEN).

• 2007-2010 PARTNERSHIP PNCDI-2 Grant, partners: University of Medicine and Pharmacy „Carol Davila”, NationalInstitute for Food Chemistry and National Institute for Diabetes, Nutrition and Metabolic Diseases „N. Paulescu”, The study of the cellular, molecular and genetic mechanisms by which dyslipidemia induces insulin resistance; identification of probiotic active compounds and treatment methods (LIPIDERI).

• 2012-2016 PARTNERSHIP PNCDI-2 Grant, partner: Cardiology Clinic of University Emergency Hospital Elias, New predictive biomarkers for the evolution of the stable and unstable coronary artery disease identified by lipidomic, proteomic and molecular biology technologies (BIOMARCAD).

b. Genetics, epigenetics and molecular biology

• 2004-2006 BIOTECH PNCDI Grant, The employment of APOA5 and APOE gene polymorphisms as molecular markers in the study of evaluation of genetic risk factors of subjects with obesity and its associated disorders (diabetes, hypertension and atherosclerosis).

• 2008-2011 IDEI PNCDI-2 Grant, Molecular strategies for the reversal of atherosclerotic process by the modulation of secretion and cellular signaling pathways and intracellular assembly of anti-atherogenic lipoproteins.

• 2015-2017 Young Teams Research Grant, Assessment of molecular strategies to improve atherogenic dyslipidemia by modulating the microRNAs expression (THERAMIR).

Studies in experimental models of the molecular mechanism of lipoprotein metabolism

• 2001-2003 VIASAN PNCDI Grant, The role of endothelium in atheroma formation: the comparative study on protective effect of various statins on cells from atherosclerotic plaque.

• 2005-2007 IDEI PNCDI Grant, The role of transcription factors PPARa and PPARg in the regulation of genes for atherogenic lipoprotein receptors on endothelial and smooth muscle cells.

• 2015-2017 Young Teams Research Grant, Molecular mechanisms of hyperlipidemia-induced insulin resistance; metabolic connections between the intestine, liver steatosis and atherosclerosis (MECLIPINSMETAB).

AWARDS

• “Victor Babes” Prize of the Romanian Academy, for experimental studies of cellular and molecular events initiating atherosclerosis, 1990 (Anca V. Sima, Rozalia Mora).

• “Constantin Velican” Prize of the Romanian Society for Cell Biology: 1994 (Anca V. Sima), 1995 (Anca Dobrian), 1998 (Daniela Tirziu), 2010 (Camelia S. Stancu), 2017 (Loredan S. Niculescu).

• “Sanofi” Thrombosis Award - for Atherosclerosis and Thrombosis Research, for clinical and laboratory research on atherothrombosis, 1998 (Anca V. Sima, Camelia S. Stancu).

• “Maya and Nicolae Simionescu” Award of the Romanian Society for Cell Biology for research on cellular and molecular biology and pathology, 1999 (Anca V. Sima).

• “Images in Cellular – Molecular Medicine” Award of the Foundation of Cellular and Molecular Medicine and the Journal of Cellular and Molecular Medicine, 2003 (Anca V. Sima).

• “Herbert Berler” Award for Excellence in Research, 2012 (Loredan S. Niculescu, Gabriela M. Sanda, Anca V. Sima).

• “Nicolae Simionescu” Prize of the Romanian Academy, 2015 (Camelia S. Stancu, Loredan S. Niculescu).

• Romanian Cardiology Society Award for Excellence in Research, 2016 (The Lipidomics team).

SELECTED List of published papers in JOURNALS indexed in Web of Science (2007 - 2019)

Toma L., Sanda G.M., Niculescu L.S., Deleanu M., Sima A.V., Stancu C.S. Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases. Biomolecules. 10(4): E641, 2020; doi.org/10.3390/biom10040641 (IF 4.694, Q1).

Toma L., Sanda G.M., Raileanu M., Stancu C.S., Niculescu L.S., Sima A.V. Ninjurin-1 upregulated by TNFα receptor 1 stimulates monocyte adhesion to human TNFα-activated endothelial cells; benefic effects of amlodipine. Life Sci. 249:117518, 2020; doi.org/10.1016/j.lfs.2020.117518 (IF 3.448, Q2).

Barbălată T., M. Deleanu, M.G. Cărnuță, L.S. Niculescu, M. Răileanu, A.V. Sima, C.S. Stancu. Hyperlipidemia Determines Dysfunctional HDL Production and Impedes Cholesterol Efflux in the Small Intestine: Alleviation by Ginger Extract. Mol. Nutr. Food Res. e1900029, 2019; doi.org/10.1002/mnfr.201900029 (IF 4.653, Q1).

Niculescu L.S., M.D. Dulceanu, C.S. Stancu, M.G. Cărnuţă, T. Barbălată, A.V. Sima. Probiotics administration or the high-fat diet arrest modulates microRNAs levels in hyperlipidemic hamsters. Journal Functional Foods 56: 295–302, 2019; doi.org/10.1016/j.jff.2019.03.036 (IF 3.197, Q1).

Cărnuță M. G., ⁠M. Deleanu⁠⁠, T. Barbălată, L. Toma⁠, M. Răileanu⁠, A. V. Sima, C. S. Stancu. Zingiber officinale extract administration diminishes steroyl-CoA desaturase gene expression and activity in hyperlipidemic hamster liver by reducing the oxidative and endoplasmic reticulum stress. Phytomedicine. 48: 62-69, 2018 doi.org/10.1016/j.phymed.2018.04.059 (IF 3.610, Q1).

Niculescu L. S., N. Simionescu, E. V. Fuior, C. S. Stancu, M. G. Cărnuță, M. D. Dulceanu, M. Răileanu, E. Drăgan, A. V. Sima. Inhibition of miR-486 and miR-92a decreases liver and plasma cholesterol levels by modulating lipid-related genes in hyperlipidemic hamsters. Molecular Biology Reports 45(4): 497-509, 2018 doi.org/10.1007/s11033-018-4186-8.

Alexandru N., E. Andrei, L.S. Niculescu, E. Dragan, V. Ristoiu, A. Georgescu. Microparticles of healthy origins improve endothelial progenitor cell dysfunction via microRNA transfer in an atherosclerotic hamster model. Acta Physiol (Oxf). 221(4): 230-249, 2017 doi.org/10.1111/apha.12896 (IF 4.867, Q1).

Toma L., G.M. Sanda, L.S. Niculescu, M Deleanu, C. Stancu, A.V. Sima. Caffeic acid attenuates the inflammatory stress induced by glycated LDL in human endothelial cells by mechanisms involving inhibition of AGE-receptor, oxidative and endoplasmic reticulum stress. Biofactors 43(5): 685-697, 2017 doi.org/10.1002/biof.1373 (IF 3.23, Q1).

Cărnuță M.G., C..S Stancu, L. Toma, G.M. Sanda, L.S. Niculescu, M. Deleanu, A.C. Popescu, M.R Popescu, A. Vlad, D.R. Dimulescu, M. Simionescu, A.V. Sima. Dysfunctional high-density lipoproteins have distinct composition, diminished anti-inflammatory potential and discriminate acute coronary syndrome from stable coronary artery disease patients. Scientific Reports 7(1): 7295, 2017 doi.org/10.1038/s41598-017-07821-5. (IF 4.26, Q1).

Sanda G.M., M. Deleanu, L. Toma, C.S. Stancu, M Simionescu, A.V. Sima. Oxidized LDL-exposed human macrophages display increased MMP-9 expression and secretion mediated by endoplasmic reticulum stress. J Cell Biochem. 118(4): 661-669, 2017 doi.org/10.1002/jcb.25637 (IF 3.08, Q2).

Simionescu N., L. S. Niculescu, G.M. Sanda, M.G. Cărnuţă, C.S. Stancu, A.C. Popescu, M.R. Popescu, A. Vlad, D.R. Dimulescu, M. Simionescu, A.V. Sima. Hyperglycemia determines increased specific microRNAs levels in sera and HDL of acute coronary syndrome patients and stimulates microRNAs production in human macrophages. PLoS One 11(8): e0161201, 2016 doi.org/10.1371/journal.pone.0161201 (IF 3.54, Q1).

Niculescu L.S., N. Simionescu, G.M. Sanda, M.G. Cărnuţă, C.S. Stancu, A.C. Popescu, M.R. Popescu, A. Vlad, D.R. Dimulescu, M. Simionescu, A.V. Sima.MiR-486 and miR-92a identified in circulating HDL discriminate between stable and vulnerable coronary artery disease patients. PLoS One 10(10): e0140958, 2015 doi.org/10.1371/journal.pone.0140958 (IF 3,057, Q1).

Stancu C.S., Carnuta M.G., Sanda G.M., Toma L., Deleanu M., Niculescu L.S., Sasson S., Simionescu M., Sima A.V. Hyperlipidemia-induced hepatic and small intestine ER stress and decreased paraoxonase 1 expression and activity is associated with HDL dysfunction in Syrian hamsters. Mol. Nutr. Food Res. 59(11): 2293-302, 2015 doi.org/10.1002/mnfr.201500422 (IF 4.259, Q1).

Stancu C.S., Sanda G.M., Deleanu M., Sima A.V. Probiotics determine hypolipidemic and antioxidant effects in hyperlipidemic hamsters, Mol. Nutr. Food Res., 58(3): 559-568, 2014 doi.org/10.1002/mnfr.201300224 (IF 4.259, Q1).

Simionescu N., Niculescu L.S., Sanda G.M., Margina D., Sima A.V. Analysis of circulating microRNAs that are specifically increased in hyperlipidemic and/or hyperglycemic sera. Molecular Biology Reports, 41(9): 5765-5773, 2014 doi.org/10.1007/s11033-014-3449-2.

Niculescu L.S., Sanda G.M., Sima A.V. HDL inhibit endoplasmic reticulum stress by stimulating apoE and CETP secretion from lipid-loaded macrophages. Biochem. Biophys. Res. Commun. 434: 173–178, 2013.

Stancu C.S., Toma L, Sima A.V. Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis. Cell Tissue Res. 349(2):433-46, 2012.

Niculescu L.S., M.R. Robciuc, G.M. Sanda, A.V. Sima. Apolipoprotein A-I stimulates cholesteryl ester transfer protein and apolipoprotein E secretion from lipid-loaded macrophages; the role of NF-κB and PKA signaling pathways. Biochem Biophys Res Commun. 415(3): 497-502, 2011.

Toma L, Stancu C.S., Sanda G.M., Sima A.V., Anti-oxidant and anti-inflammatory mechanisms of amlodipine action to improve endothelial cell dysfunction induced by irreversibly glycated LDL. Biochem Biophys Res Commun. 411(1): 202- 207, 2011.

Constantinescu E., Safciuc F., Sima A.V., A Hyperlipidemic Diet Induces Structural Changes in Cerebral Blood Vessels, Current Neurovascular Research, 8(2):131-44, 2011.

Heltianu C., Robciuc A., Botez G., Musina C., Stancu C., Sima A.V., Simionescu M., Modified Low Density Lipoproteins decrease the activity and expression of lysosomal acid lipase in human endothelial and smooth muscle cells. Cell Biochemistry and Biophysics, 61(1): 209-16, 2011.

Sima A.V., Botez GM, Stancu CS, Manea A, Raicu M, Simionescu M. Effect of irreversibly glycated LDL in human vascular smooth muscle cells: Lipid loading, oxidative and inflammatory stress. J. Cell. Mol. Med. 14: 2790-2802, 2010 (IF 4.499, Q1).

Niculescu L.S., M. Vlădică, A.V. Sima. Association of APOA5 and APOC3 gene polymorphisms with plasma apolipoprotein A5 level in patients with metabolic syndrome. Biochem. Biophys. Res. Comm. 391(1): 587–591, 2010.

Constantin A, Costache G, Sima AV, Glavce CS, Vladica M, Popov DL. Leptin G-2548A and leptin receptor Q223R gene polymorphisms are not associated with obesity in Romanian subjects. Biochem Biophys Res Commun. 391(1): 282-286, 2010.

Robciuc MR, Metso J, Sima A, Ehnholm C, Jauhiainen M., Human apoA-I increases macrophage foam cell derived PLTP activity without affecting the PLTP mass. Lipids Health Dis. 9: 59-65, 2010.

Toma L, Stancu CS, Botez GM, Sima AV, Simionescu M. Irreversibly glycated LDL induce oxidative and inflammatory state in human endothelial cells; added effect of high glucose. Biochem. Biophys. Res. Commun. 390(3):877-82, 2009.

Simionescu M., D. Popov, A.V. Sima. Endothelial transcytosis in health and disease. Cell Tissue Res. 335(1):27-40, 2009.

Sima AV, Stancu C., Simionescu M. Vascular endothelium in atherosclerosis. Cell Tissue Res. 335(1):191-203, 2009.

Sima A.V., A. Iordan, C. Stancu. Apolipoprotein E polymorphism – a risk factor for the metabolic syndrome. Clin. Chem. Lab. Med. 45(9): 1149-53, 2007 (IF 3.432, Q1).

Niculescu L.S., J. Fruchart-Najib, J.-C. Fruchart, A.V. Sima. Apolipoprotein A-V gene polymorphisms in subjects with metabolic syndrome. Clin. Chem. Lab. Med. 45(9): 1133-9, 2007 (IF 3.432, Q1).

LABORATORY: Liquid and gas chromatography (Core Laboratory Unit)

STAFF

Mariana DELEANU, chemical engineer

Chromatographic analysis of fatty acids, oxidized lipids, vitamins.

LABORATORIES

• Lipoproteins and atherosclerosis

• Molecular biology of lipoproteins

• Liquid and gas chromatography (Core Laboratory Unit)

Infrastructure link in ERRIS platform: https://erris.gov.ro/Department-of-Lipidomics-1

Major positions and appointments

Anca V. SIMA

Head of department

(email me)

STAFF

LABORATORY: Liquid and gas chromatography (Core Laboratory Unit)

Infrastructure link in ERRIS platform:
https://erris.gov.ro/Department-of-Lipidomics-1