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Laboratory of Cellular Pharmacology of Atherosclerosis  

lab prof Corsini

 

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.

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, lipidomic and proteomic analyses, with the ultimate 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

Paul Quax, Einthoven Laboratory for Experimental Vascular Medicine, Department of Surgery, LUMC Leiden, Olanda
Guido De Meyer, Departement Farmaceutische Wetenschappen, Campus Drie Eiken Universiteitsplein, Antwerp, Belgio
Damien Breheny, British American Tobacco, Southampton, UK
Maria Luisa Gelmi, DiSFarm, Università degli Studi di Milano, Italia
Marina Carini, DiSFarm, Università degli Studi di Milano, Italia
Ermanno Valoti, DiSFarm, Università degli Studi di Milano, Italia
Francesco Cilurzo, DiSFarm, Università degli Studi di Milano, Italia
Licia Rivoltini, Istituto Nazionale Tumori, Milano, Italia
Giulio Pompilio, Centro Cardiologico Monzino, Milano, Italia
Gaia Spinetti, IRCCS Multimedica, Milano, Italia
Paolo Madeddu, Bristol Heart Institute, Bristol, UK
Roberta Fruttero, Dip. Scienze del Farmaco, Università degli Studi di Torino, Italia


Selected publications

Recombinant LCAT rescues defective HDL mediated endothelial protection in acute coronary syndrome. Ossoli A, Simonelli S, Varrenti M, Morici N, Oliva F, Stucchi M, Gomaraschi M, Strazzella A, Arnaboldi L, Thomas M, Sorci-Thomas M, Corsini A, Veglia F, Franceschini G, Karathanasis S, Calabresi L. Arterioscler Thromb Vasc Biol. 2019 May;39(5):915-924

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.

ABCA1 and HDL3 are Required to Modulate Smooth Muscle Cells Phenotypic Switch after Cholesterol Loading. Castiglioni S, Monti M, Arnaboldi L, Canavesi M, Ainis Buscherini G, Calabresi L, Corsini A, Bellosta S. Atherosclerosis. 2017 Nov; 266:8-15.

Cigarette smoke condensate affects monocyte interaction with endothelium. Giunzioni I, Bonomo A, Bishop E, Castiglioni S, Corsini A, Bellosta S. Atherosclerosis 2014, 234:383-390.

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