Research topics

Main objective of the research activity of our lab is to improve the understanding of the pathophysiology of human lipoproteins and the mechanism of action of lipid-lowering and anti-atherosclerotic drugs. Specifically:

• genetic, biochemical and clinical characterization of carriers of genetic disorders of lipid metabolism
• role of the lecithin:cholesterol acyltransferase enzyme in lipid/lipoprotein metabolism and in pathological conditions, such as acute coronary syndrome and renal disease 
• evaluation of the anti-tumor properties of HDL in prostate cancer 
• study of the efficacy and mechanism of action of lipid-lowering and anti-atherosclerotic therapies in dyslipidemic patient 
• investigation of the effects of novel dietary or pharmacologic treatments on atherosclerosis development and regression, in vivo, by invasive and non-invasive techniques, and ex-vivo by histology.
• identification of new molecular targets for dyslipidemia and atherosclerosis treatment through transcriptomic, lipidomic and miRNomic approaches.

 

Techniques

• Separation and characterization of plasma lipoproteins: ultracentrifugation, chromatography, electrophoresis (SDS-PAGE, IEF, bidimensional electrophoresis), immunoassays
• Cell cultures: endothelial cells, primary monocytes, renal cells (tubular, mesangial, podocytes), cardiomyocytes, prostatic cells (cancer, epithelial) hepatocytes
• Molecular biology: gene sequencing, PCR, q-PCR, cell and tissue RNA extraction, Western blotting.
• Animal models: generation and characterization of genetically modified mice for the study of dyslipidemias and atherosclerosis development; atherosclerosis induction in rabbits through perivascular electrical damage; histological and molecular analyses. 
• In vivodiagnostics: intravascular ultrasound and magnetic resonance imaging in rabbits and mice; quantification of atherosclerotic plaques.

 

Collaborators

• Dr. Alan Remaley, NIH, USA
• Prof. Erik SG Stroes, University of Amsterdam, The Netherlands
• Prof. Dagmar Kratky, University of Graz, Austria
• Prof. Paolo Parini, Karolinska University Hospital, Stockholm, Sweden
• Dr. Philippe Gérard, INRA, Micalis Institute, Jouy-en-Josas, France
• Dr. Marcus Kleber, Heidelberg University, Mannheim, Germany
• Dr. Reijo Laaksonen, University of Tampere, Tampere, Finland
• Prof. Marcello Arca, Università degli Studi di Roma “La Sapienza”
• Prof. Franco Bernini//Dr.ssa Francesca Zimetti - Università degli Studi di Parma 
• Prof. Lucio Tremolizzo, Università degli Studi di Milano-Bicocca
• Prof. Eugenio Scanziani, Università degli Studi di Milano

 

Selected publications

1. Ossoli A, Simonelli S, Varrenti M, Morici N, Oliva F, Stucchi M, Gomaraschi M, Strazzella A, Arnaboldi L, Thomas MJ, Sorci-Thomas MG, Corsini A, Veglia F, Franceschini G, Karathanasis SK, Calabresi L. Recombinant LCAT (Lecithin:Cholesterol Acyltransferase) Rescues Defective HDL (High-Density Lipoprotein)-Mediated Endothelial Protection in Acute Coronary Syndrome. Arterioscler Thromb Vasc Biol. 2019 Mar 21:ATVBAHA118311987.
2. Manzini S, Busnelli M, Parolini C, Minoli L, Ossoli A, Brambilla E, Simonelli S, Lekka E, Persidis A, Scanziani E, Chiesa G. Topiramate protects apoE-deficient mice from kidney damage without affecting plasma lipids. Pharmacol Res. 2019 Mar;141:189-200.
3. Ruscica M, Botta M, Ferri N, Giorgio E, Macchi C, Franceschini G, Magni P, Calabresi L, Gomaraschi M. High Density Lipoproteins Inhibit Oxidative Stress-Induced Prostate Cancer Cell Proliferation. Sci Rep. 2018 Feb 2;8(1):2236.
4. D'Erasmo L, Minicocci I, Nicolucci A, Pintus P, Roeters Van Lennep JE, Masana L, Mata P, Sánchez-Hernández RM, Prieto-Matos P, Real JT, Ascaso JF, Lafuente EE, Pocovi M, Fuentes FJ, Muntoni S, Bertolini S, Sirtori C, Calabresi L, Pavanello C, Averna M, Cefalu AB, Noto D, Pacifico AA, Pes GM, Harada-Shiba M, Manzato E, Zambon S, Zambon A, Vogt A, Scardapane M, Sjouke B, Fellin R, Arca M. Autosomal Recessive Hypercholesterolemia: Long-Term Cardiovascular Outcomes. J Am Coll Cardiol. 2018 Jan 23;71(3):279-288.
5. Busnelli M, Manzini S, Hilvo M, Parolini C, Ganzetti GS, Dellera F, Ekroos K, Jänis M, Escalante-Alcalde D, Sirtori CR, Laaksonen R, Chiesa G. Liver-specific deletion of the Plpp3 gene alters plasma lipid composition and worsens atherosclerosis in apoE-/- mice. Sci Rep. 2017 Mar 14;7:44503.