Lorenzo Da Dalt

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Verified

Lorenzo verified their affiliation via an institutional email.

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• PhD
• PostDoc Position at University of Milan

Tregs for adoptive therapy are traditionally expanded ex vivo using high doses of IL-2. However, the final Treg product has limited survival once infused in patients, potentially affecting therapeutic effectiveness. Here, we tested a novel expansion protocol in which highly purified naïve Tregs were expanded with a combination of IL-7 and IL-15, in...

Angiopoietin-like 3 (ANGPTL3) is a lipases-inhibiting hepatokine, thus prevents VLDL and LDL-derived triglycerides, regulating fluxes of triglycerides to the tissues. Aim of this study is to investigate the association between hypolipidemia-induced metabolic alteration, due to ANGPTL3 deficiency, and potential hepatic responses, depending on the so...

Background and Aims: Neutrophils participate to the chronic metabolic consequences of High Fat Diet (HFD). Nevertheless, neutrophils are characterized by short half-life which is determined by a fine tuning in expression and function of CXCR4, which dictates the egress from the bone marrow (BM), and CXCR2, which facilitates their mobilization from...

Background: Kupffer cells (KCs) are hepatoresident macrophages that are essential for liver physiology and contribute to the development of nonalcoholic hepatic steatosis (NAFLD). The liver of patients with MAFLD shows different expressions of some key regulators of inner mitochondrial membrane fusion compared with healthy subjects, including OPA1...

The asialoglycoprotein receptor 1 (ASGR1), a multivalent carbohydrate-binding receptor that primarily is responsible for recognizing and eliminating circulating glycoproteins with exposed galactose (Gal) or N-acetylgalactosamine (GalNAc) as terminal glycan residues, has been implicated in modulating the lipid metabolism and reducing cardiovascular...

Purpose Contemporary guidelines for the prevention of cardio-metabolic diseases focus on the control of dietary fat intake, because of their adverse metabolic effects. Moreover, fats alter innate immune defenses, by eliciting pro-inflammatory epigenetic mechanisms on the long-living hematopoietic cell progenitors which, in the bone marrow, mainly g...

Background: Elevated levels of lipoprotein(a) [Lp(a)] represent a risk factor for cardiovascular disease including aortic valve stenosis, myocardial infarction and stroke. While the patho-physiological mechanisms linking Lp(a) with atherosclerosis are not fully understood, from genetic studies that lower Lp(a) levels protect from CVD independently...

Aim: ANGPTL3 controls lipid and lipoprotein metabolism through lipoprotein lipase and endothelial lipase inhibition and the prevention of lipoprotein-derived triglycerides hydrolyzation. Here we present the metabolic profile of ANGPTL3 deficient mice in physiology and during the development of metabolic disorders. Methods: Angptl3 KO mice (C57BL6/J...

Aim: The epigenetic modifications induced by High Fat Diets (HFDs) in long-living hematopoietic cells have been well described, but whether they affect the “aging” of neutrophils, characterized by far shorter half-life, is less clear. Neutrophils "age" through a reciprocal regulation of CXCR4, promoting a "fresh" status when leaving the BM, and CXC...

Background Asialoglycoprotein receptor 1 (ASGR1), primarily expressed on hepatocytes, promotes the clearance and the degradation of glycoproteins, including lipoproteins, from the circulation. In humans, loss-of-function variants of ASGR1 are associated with a favorable metabolic profile and reduced incidence of cardiovascular diseases. The molecul...

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide; however, the underlying causes of AF initiation are still poorly understood, particularly because currently available models do not allow in distinguishing the initial causes from maladaptive remodeling that induces and perpetuates AF. Lately, the genetic background has been...

Aims Mitochondria are plastic organelles that continuously undergo biogenesis, fusion, fission, and mitophagy to control cellular energy metabolism, calcium homeostasis, hormones, sterols, and bile acids (BAs) synthesis. Here, we evaluated how the impairment of mitochondrial fusion in hepatocytes affects diet-induced liver steatosis and obesity. M...

A fine balance between uptake, storage and the use of high energy fuels, like lipids, is crucial in the homeostasis of different metabolic tissues. Nowhere is this balance more important and more precarious than in the heart. This highly energy demanding muscle normally oxidizes almost all the available substrates to generate energy, with fatty aci...

Background and aim: The primary transcript of fibronectin (FN) undergoes alternative splicing to generate different isoforms, including FN containing the Extra Domain A (FN_EDA+), whose expression is regulated spatially and temporarily during developmental and disease conditions including acute inflammation. The role of FN_EDA+ during sepsis, howe...

Background: Obesity-related fat accumulation is linked to the metabolic syndrome and increases the risk of CVD by involving FFA, insulin resistance, and inflammation. Taking into account the findings from the third chapter, our goal was to assess the potential role of ASGR1 in metabolic reprogramming and immunoinflammatory state during obesity. Met...

The VIII Spring Meeting of Young Researchers of the Italian Society of Diabetology (SID), the Italian Society of Arterial Hypertension (SIIA), the Italian Society of Internal Medicine (SIMI), the Italian Society of Cardiovascular Prevention (SIPREC) and the Italian Society for the Study of Atherosclerosis (SISA) “Basic and clinical research: Until...

Background: High fat diet (HFD) chronically hyper-activate the myeloid cell precursors, but whether it affects the neutrophil aging is unknown. Purpose: We characterized how HFD impacts neutrophil aging, infiltration in metabolic tissues and if this aging, in turn, modulates the development of metabolic alterations. We immunophenotyped neutrophi...

The mannose receptor C-type 1 (Mrc1) is a C-type lectin receptor expressed on the immune cells and sinusoidal endothelial cells (ECs) of several tissues, including the bone marrow (BM). Parallel to systemic metabolic alterations and hematopoietic cell proliferation, high-fat diet (HFD) feeding increases the expression of Mrc1 in sinusoidal ECs, thu...

Introduction: in liver, mitochondria continuously undergo biogenesis, fusion, fission and mitophagy, and thus participate to the regulation of energy metabolism, calcium homeostasis and lipid metabolism. Hypothesis: test the role of selective deletion of a key protein involved in inner mitochondrial membrane fusion (OPA1) in hepatocytes on mitochon...

The Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) protease is a 692 amino acid glycoprotein which belongs to the proprotein convertase family. PCSK9 binds several receptors of the LDL family, including VLDLR, LRP1 but also with CD36, driving their lysosomal degradation. From the beginning of the 21st century a growing body of interest raise...

Background: Cholesterol is central to pancreatic β-cell physiology and alterations of its homeostasis contribute to β-cell dysfunction and diabetes. Proper intracellular cholesterol levels are maintained by different mechanisms including uptake via the low-density lipoprotein receptor (LDLR). In the liver, the proprotein convertase subtilisin/kexi...

Kupffer cells (KCs) are tissue-resident macrophages of the liver, that play crucial roles in liver physiopathology. In addition to a pure immunology action, they synthesize proteins with a metabolic activity that affects systemic metabolism (i.e., CETP). The OPA1 protein is a member of the dynamine family located in the mitochondrial inner membrane...

The molecular pathophysiology of cardiometabolic diseases is known to be influenced by dysfunctional ectopic adipose tissue. In addition to lifestyle improvements, these conditions may be managed by novel nutraceutical products. This study evaluatedthe effects of 11 Cameroonian medicinal spice extracts on triglyceride accumulation, glucose uptake,...

Aims PCSK9 is secreted into the circulation, mainly by the liver, and interacts with low-density lipoprotein receptor (LDLR) homologous and non-homologous receptors, including CD36, thus favouring their intracellular degradation. As PCSK9 deficiency increases the expression of lipids and lipoprotein receptors, thus contributing to cellular lipid ac...

Rivaroxaban (RVX) was suggested to possess anti-inflammatory and vascular tone modulatory effects. The goal of this study was to investigate whether RVX impacts lipopolysaccharide (LPS)-induced acute vascular inflammatory response. Male rats were treated with 5 mg/kg RVX (oral gavage) followed by 10 mg/kg LPS i.p injection. Circulating levels of IL...

Aims Leucocyte telomere length (LTL) shortening is a marker of cellular senescence and associates with increased risk of cardiovascular disease (CVD). A number of cardiovascular risk factors affect LTL, but the correlation between elevated LDL cholesterol (LDL-C) and shorter LTL is debated: in small cohorts including subjects with a clinical diagno...

Metabolic reprogramming is a physiological cellular adaptation to intracellular and extracellular stimuli that couples to cell polarization and function in multiple cellular subsets. Pathological conditions associated to nutrients overload, such as dyslipidaemia, may disturb cellular metabolic homeostasis and, in turn, affect cellular response and...

Cholesterol plays an essential role in determining cell membrane physico-chemical characteristics and functions. A proper membrane structure is critical in pancreatic β-cells for glucose-mediated insulin secretion, and alterations in cellular cholesterol content may negatively affect this process, leading to β-cell dysfunction. The low density lipo...

Aims: It has been hypothesized that the activity of lysosomal acid lipase (LAL), a key enzyme involved in lipid metabolism, is involved in the NAFLD phenotype. To clarify the role of LAL in NAFLD, we studied 164 consecutive patients with biopsy-proven NAFLD and fat-loaded HepG2 cells. Methods: LAL activity was measured (i) on dried blood spots (...

Cholesterol homeostasis has a pivotal function in regulating immune cells. Here we show that apolipoprotein E (apoE) deficiency leads to the accumulation of cholesterol in the cell membrane of dendritic cells (DC), resulting in enhanced MHC-II-dependent antigen presentation and CD4+ T-cell activation. Results from WT and apoE KO bone marrow chimera...

Aims: PCSK9 loss of function genetic variants are associated with lower low-density lipoprotein cholesterol but also with higher plasma glucose levels and increased risk of Type 2 diabetes mellitus. Here, we investigated the molecular mechanisms underlying this association. Methods and results: Pcsk9 KO, WT, Pcsk9/Ldlr double KO (DKO), Ldlr KO,...