Research topics

Our interest is focused on the physiopathology, biochemistry and pharmacological regulation of atherosclerosis, obesity, NAFLD, metabolic syndrome, bone and vascular aging. We perform studies on cellular (macrophages, endothelial and smooth muscle cells) and molecular biology, inflammation and proliferative processes, lipid and lipoprotein biochemistry.

Cholesterol and cigarette smoke in atherogenesis: effects on vascular cells
Cigarette smoke and cholesterol are important risk factors for atherosclerosis. Our goal is to evaluate the effects of cigarette smoke on monocyte/macrophage-endothelial cells interaction(s) in atherogenesis. Recent data demonstrate that, beyond cholesterol, also cigarette smoke can cause a phenotypic change in smooth muscle cells. We will evaluate the mechanisms responsible for these effects and particularly the epigenetic regulation of genes involved in atherogenesis. Moreover, we will evaluate the pathogenic effect(s) of new cigarette types, such as e-cigarette and heat-not burning devices.

Extracellular vesicles (EV) and physiopathological functions
EV are secreted by cells and classified, based on their dimensions and origin, in exosomes and microvesicles. Thanks to their content, they are involved in cell communication processes and are likely to play a pivotal role in inflammation and tumors. To comprehend their function, our aim is to characterize and separate various EV populations by centrifugation, and lipidomic and proteomic analyses, with the goal to pharmacologically modify and utilize them in functional assays.

Techniques

The lab is totally equipped for the isolation and maintenance of primary and continuous cell lines.

In vitro assays

• Proliferation by cell count (Coulter counter), real-time monitoring of cell behaviour(iCELLigence) and cell-cycle analysis (cytofluorimeter)
• Chemotaxis (Boyden chamber) and cell transmigration
• Western blot, dot-blot, zymography, ELISA, EIA and G-LISA
• Quantitative RT-PCR by ABI Prism 7000 Thermocycler (Applied Biosystem)
• Gene overexpression and silencing in primary vascular cell lines by viral vectors and siRNA
• Lipoprotein and extracellular vesicles separation by ultracentrifugation

In vivo assays

• Murine models of atherosclerosis and NAFLD

Other experimental techniques

• Lipidomics (TLC, GLC with FID detector DANI GC1000 and HTA autosampler, HPLC Jasco with UV detector, colorimetric assays) of simple and complex lipids from different biological matrices (cells, medium, tissues, plasma, lipoproteins)

Collaborations

International collaborations
Paul Quax, Einthoven Laboratory for Experimental Vascular Medicine, Department of Surgery, LUMC Leiden, The Netherland
Guido De Meyer, DepartementFarmaceutischeWetenschappen, Campus DrieEikenUniversiteitsplein, Antwerp, Belgium
Damien Breheny, British American Tobacco, Southampton, UK

National collaborations
Laura Calabresi, DiSFeB - Università degli Studi di Milano
Paolo Magni, DiSFeB - Università degli Studi di Milano
Danilo Norata, DiSFeB - Università degli Studi di Milano
Maria Luisa Gelmi, DISFARM - Università degli Studi di Milano
Marina Carini, DISFARM - Università degli Studi di Milano
Ermanno Valoti, DISFARM - Università degli Studi di Milano
Francesco Cilurzo, DISFARM - Università degli Studi di Milano
Luigi Sironi, DISFARM - Università degli Studi di Milano
Alessandra Puglisi, Department of Chemistry - Università degli Studi di Milano
Mario Cozzolino, Nefrologia Ospedale San Paolo - Università degli Studi di Milano
Licia Rivoltini, Istituto Nazionale Tumori, Milano
Monica Rodolfo, Istituto Nazionale Tumori, Milano
Giulio Pompilio, Monzino Cardiology Center, Milano
Silvia Stella Barbieri, Monzino Cardiology Center, Milano
Franco Bernini, Università degli Studi di Parma
Andrea Ridolfi, Department of Chemistry, University of Florence, Sesto Fiorentino
Roberta Fruttero, Università degli Studi di Torino
Paolo Bergese, Department of Molecolar and Translational Medicine, Università di Brescia

Selected publications

LIPA gene mutations affect the composition of lipoproteins: Enrichment in ACAT-derived cholesteryl esters.
Arnaboldi L, Ossoli A, Giorgio E, Pisciotta L, Lucchi T, Grigore L, Pavanello C, Granata A, Pasta A, Arosio B, Azzolino D, Baragetti A, Castelnuovo S, Corsini A, Catapano AL, Calabresi L, Gomaraschi M.
Atherosclerosis. 2020 Jan 31;297:8-15.

BDNF Val66Met polymorphism affects macrophage polarization after myocardial infarction.
L. Sandrini, L. Castiglioni, P. Amadio, J.P. Werba, S. Eligini, S. Fiorelli, M. Zarà, S. Castiglioni, S. Bellosta, F.S. Lee, L. Sironi, E. Tremoli, S.S. Barbieri.
Cells 2020, 9, 1084

Treatment of dyslipidemia in kidney transplantation.
Ponticelli C, Arnaboldi L, Moroni G, Corsini A.
Expert Opin Drug Saf. 2020 Mar 2:1-11.

PCSK9 deficiency reduces insulin secretion and promotes glucose intolerance: the role of the low-density lipoprotein receptor.
Da Dalt L, Ruscica M, Bonacina F, Balzarotti G, Dhyani A, Di Cairano E, Baragetti A, Arnaboldi L, De Metrio S, Pellegatta F, Grigore L, Botta M, Macchi C, Uboldi P, Perego C, Catapano AL, Norata GD.
Eur Heart J. 2019 Jan 21;40(4):357-368.

Statin drug interactions and related adverse reactions: an update.
Bellosta S, Corsini A.
Expert Opin Drug Saf. 2018, 17(1):25-37.