Research Objectives

The main objective of the research is the study of lipid and lipoprotein metabolism in relation to cardiometabolic and immuno-inflammatory diseases in order to identify new drug targets.
The research lines can be divided into:

• Study of the role of proteins related to lipoprotein metabolism and cardiometabolic outcome. The main objective is to study how proteins that regulate receptor expression for LDL (eg PCSK9) can influence cellular metabolism of cholesterol and other lipids not only in the liver, but also in other tissues such as pancreas, heart and brain.
• Study of the role of apolipoproteins and their receptors in regulating the immune response. The main objective is to understand the role of apolipoprotein E and key receptors of lipoprotein metabolism (eg LDL-R) in modulating cholesterol metabolism in immune cells and how this can be reflected in the regulation of the immunometabolic response.
• Study of mitochondrial plasticity in modulating intracellular energy metabolism at vascular level and its impact on atherosclerosis, with particular reference to mitochondrial fusion proteins (eg OPA-1).
• Study of the role of receptors involved in the recognition of glycosylated proteins in the regulation of lipid metabolism in the liver and its involvement in atherogenic processes, with particular interest for the ASGR1 receptor.
• Study of the impact of mutations in genes relevant for lipid and lipoprotein metabolism on immunoregulation in humans, with particular interest in mutations associated with familial hypercholesterolemia and analysis of the impact of postprandial response on endothelial activation and immune response. 

Techniques

In vitro models
Human primary endothelial cells (HUVECs), reprogrammed human stem cells (HPSc), human circulating mononuclear cells (PBMCs), blood-derived dendritic and lymphocyte cells. Primary cells derived from experimental models, cell lines (i.e. HEPG2, J774, CHO).
In vivo models
Animal models of atherosclerosis (ApoE KO, LDL-R KO) and metabolic pathologies such as obesity and insulin resistance.
Biochemistry
Circulating lipid and lipoprotein profile; isolation of lipoproteins by ultracentrifugation; FPLC; lipidomics through gas chromatography and mass spectrometry.
Pathophysiology
Study of atherosclerotic pathology through immunohistochemistry and immunofluorescence; immunophenotyping of atherosclerotic plaque by multiparametric flow cytometry.
Molecular biology and genetics
Gene and protein expression analysis by Q-PCR and western Blotting;, genomic studies through RNAseq and proteomics by mass spectrometry; evaluation of gene polymorphisms on population by allele discrimination and DNA sequencing.

 

Collaborators

A list of the main national and international collaborators:

• Università degli Studi di Padova - Prof. Alberto Zambon
• Università degli Studi di Padova - Prof. Luca Scorrano
• Università degli Studi di Napoli - Prof. Giuseppe Matarese
• IRCCS Ospedale San Raffaele Milano - Dr. Marco Magnoni
• IRCCS Multimedica Milano - Prof. Annibale Puca
• AMC  University of Amsterdam - Prof. Erik Stroes
• University of Cambridge - Prof. Brian Ference
• Imperial College of London - Prof. Kausik Ray
• Almazov National Medical Research Centre, St. Petersburg - Prof. Evgeny Shylantov
• Harvard Medical School, Boston - Prof. Joseph Loscalzo
• Queen Mary University, London - Prof. Federica Marelli-Berg
• Karolinska Institutet, Solna Sweden -  Prof. Paolo Parini
• CNIC  Spanish National Cardiovascular Research Centre, Madrid – Prof. Andres Hidalgo
• University Medical Center Hamburg – Prof. Jorg Heeren
• Charité – Universitätsmedizin Berlin - Prof. Ulf Landmesser

 

Selected Publications

Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol
Ray KK, Bays HE, Catapano AL, Lalwani ND, Bloedon LT, Sterling LR, Robinson PL, Ballantyne CM; CLEAR Harmony Trial.
N Engl J Med. 2019 Mar 14;380(11):1022-1032. doi: 10.1056/NEJMoa1803917

Pentraxin 3 deficiency protects from the metabolic inflammation associated to diet-induced obesity
Bonacina F, Moregola A, Porte R, Baragetti A, Bonavita E, Salatin A, Grigore L, Pellegatta F, Molgora M, Sironi M, Barbati E, Mantovani A, Bottazzi B, Catapano AL, Garlanda C, Norata GD.
Cardiovasc Res. 2019 Mar 12. pii: cvz068. doi: 10.1093/cvr/cvz068. [Epub ahead of print]

Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease.
Ference BA, Kastelein JJP, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, Laufs U, Oliver-Williams C, Wood AM, Butterworth AS, Di Angelantonio E, Danesh J, Nicholls SJ, Bhatt DL, Sabatine MS, Catapano AL.
JAMA. 2019 Jan 29;321(4):364-373. doi: 10.1001/jama.2018.20045. 

Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation.
Bonacina F, Coe D, Wang G, Longhi MP, Baragetti A, Moregola A, Garlaschelli K, Uboldi P, Pellegatta F, Grigore L, Da Dalt L, Annoni A, Gregori S, Xiao Q, Caruso D, Mitro N, Catapano AL, Marelli-Berg FM, Norata GD.
Nat Commun. 2018 Aug 6;9(1):3083. doi: 10.1038/s41467-018-05322-1.

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. doi: 10.1093/eurheartj/ehy357.