A5013827368- Lipoproteins and Cardiovascular Health
- Adipokines, Inflammation, and Metabolic Diseases
- Atherosclerosis and Cardiovascular Diseases
- Diet and metabolism studies
- Cancer, Lipids, and Metabolism
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Computational Drug Discovery Methods
- Lipid metabolism and disorders
- Cholesterol and Lipid Metabolism
- Metabolism and Genetic Disorders
- Liver Disease Diagnosis and Treatment
- Immune cells in cancer
- Diabetes and associated disorders
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Neonatal Respiratory Health Research
- Cell Adhesion Molecules Research
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cardiovascular Function and Risk Factors
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Dietary Effects on Health
- Nuclear Receptors and Signaling
- Lysosomal Storage Disorders Research
University of Milan
2018-2025
PCSK9 loss of function genetic variants are associated with lower low-density lipoprotein cholesterol but also higher plasma glucose levels and increased risk Type 2 diabetes mellitus. Here, we investigated the molecular mechanisms underlying this association. Pcsk9 KO, WT, Pcsk9/Ldlr double KO (DKO), Ldlr albumin AlbCre+/Pcsk9LoxP/LoxP (liver-selective knock-out mice), AlbCre-/Pcsk9LoxP/LoxP mice were used. GTT, ITT, insulin C-peptide levels, pancreas morphology, accumulation in pancreatic...
PCSK9 promotes the degradation of low-density lipoprotein receptors and its inhibition by monoclonal antibodies or gene silencing approaches results in reduction plasma cholesterol levels coupled to that cardiovascular events. Notably, while liver is primary source circulating PCSK9, this protein also abundantly expressed brain. However, specific functions brain remain poorly understood. Here, we demonstrate neuron-specific knockout mice exhibit impaired cognitive function, driven...
Cholesterol homeostasis has a pivotal function in regulating immune cells. Here we show that apolipoprotein E (apoE) deficiency leads to the accumulation of cholesterol cell membrane dendritic cells (DC), resulting enhanced MHC-II-dependent antigen presentation and CD4+ T-cell activation. Results from WT apoE KO bone marrow chimera suggest hematopoietic origin immunomodulatory functions, regardless onset hypercholesterolemia. Humans expressing apoE4 isoform (ε4/3-ε4/4) have increased...
Abstract Aims PCSK9 is secreted into the circulation, mainly by liver, and interacts with low-density lipoprotein receptor (LDLR) homologous non-homologous receptors, including CD36, thus favouring their intracellular degradation. As deficiency increases expression of lipids contributing to cellular lipid accumulation, we investigated whether this could affect heart metabolism function. Methods results Wild-type (WT), Pcsk9 KO, Liver conditional KO Pcsk9/Ldlr double male mice were fed for 20...
Abstract Background Asialoglycoprotein receptor 1 (ASGR1), primarily expressed on hepatocytes, promotes the clearance and degradation of glycoproteins, including lipoproteins, from circulation. In humans, loss-of-function variants ASGR1 are associated with a favorable metabolic profile reduced incidence cardiovascular diseases. The molecular mechanisms by which could affect onset syndrome obesity unclear. Therefore, here we investigated contribution in development obesity. Methods deficient...
PCSK9 promotes the degradation of low-density lipoprotein receptors and its inhibition by monoclonal antibodies or gene silencing approaches results in reduction plasma cholesterol levels coupled to that cardiovascular events. Notably, while liver is primary source circulating PCSK9, this protein also abundantly expressed brain. However, specific functions brain remain poorly understood.Here, we demonstrate neuron-specific knockout mice exhibit impaired cognitive function, driven alterations...
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 which highly purified naïve were with combination IL-7 and IL-15, absence The was enriched cells displaying an immature CD45RA+CD62L+CD95+ phenotype, reminiscent conventional memory stem T cells. IL-15 confers glycolytic metabolism...
Background High fat diet (HFD) chronically hyper-activates the myeloid cell precursors, but whether it affects neutrophil aging is unknown. Purpose We characterized how HFD impacts aging, infiltration in metabolic tissues and if this turn, modulates development of alterations. immunophenotyped neutrophils responses physiology (wild-type mice, WT) mice with constitutively aged (MRP8 driven conditional deletion CXCR4; herein CXCR4fl/flCre+) or fresh CXCR2; CXCR2fl/flCre+), following 20 weeks...
The mannose receptor C-type 1 (Mrc1) is a lectin expressed on the immune cells and sinusoidal endothelial (ECs) of several tissues, including bone marrow (BM). Parallel to systemic metabolic alterations hematopoietic cell proliferation, high-fat diet (HFD) feeding increases expression Mrc1 in ECs, thus calling for investigation its role reprogramming profile during obesity.
Abstract Aims Mitochondria are plastic organelles that continuously undergo biogenesis, fusion, fission, and mitophagy to control cellular energy metabolism, calcium homeostasis, hormones, sterols, bile acids (BAs) synthesis. Here, we evaluated how the impairment of mitochondrial fusion in hepatocytes affects diet-induced liver steatosis obesity. Methods results Male mice selectively lacking key protein involved inner optic atrophy 1 (OPA1) (OPA1ΔHep) were fed a high fat diet (HFD) for 20...
To the Editor, Glucose-6-phosphate (G6P) translocase (G6PT/SLC37A4) is an ubiquitously expressed enzyme and required for conversion of G6P to glucose, thus ensuring glucose production by liver kidney [1]. Biallelic loss function in G6PT/SLC37A4 causes glycogen storage disease type Ib (GSD-Ib), a rare with incidence ̴1/100,000. GSD-Ib characterized severe hypoglycemia, growth retardation, osteoporosis long-term risk tumours failure [2]. In addition, individuals G6PT deficiency also develop...
Rivaroxaban (RVX) was suggested to possess anti-inflammatory and vascular tone modulatory effects. The goal of this study investigate whether RVX impacts lipopolysaccharide (LPS)-induced acute inflammatory response. Male rats were treated with 5 mg/kg (oral gavage) followed by 10 LPS i.p injection. Circulating levels IL-6, MCP-1, VCAM-1, ICAM-1 measured in plasma 6 24 hours after injection, while isolated aorta used for gene expression analysis, immunohistochemistry, evaluation....
Abstract The asialoglycoprotein receptor 1 (ASGR1), a multivalent carbohydrate-binding 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 reducing cardiovascular disease burden. In this study, we investigated impact of ASGR1 deficiency (ASGR1 −/−) on atherosclerosis by evaluating its effects plaque formation,...
The molecular pathophysiology of cardiometabolic diseases is known to be influenced by dysfunctional ectopic adipose tissue. In addition lifestyle improvements, these conditions may managed novel nutraceutical products. This study evaluatedthe effects 11 Cameroonian medicinal spice extracts on triglyceride accumulation, glucose uptake, reactive oxygen species (ROS) production and interleukin secretion in SW 872 human adipocytes after differentiation with 100 µM oleic acid. Triglyceride...
Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide; however, underlying causes of AF initiation are still poorly understood, particularly because currently available models do not allow in distinguishing initial from maladaptive remodeling that induces and perpetuates AF. Lately, genetic background has been proven to be important onset. iPSC-derived cardiomyocytes, being patient- mutation-specific, may help solve this diatribe by showing cell-autonomous changes...