A5090184233- Heat shock proteins research
- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- Protein Kinase Regulation and GTPase Signaling
- Cardiac Fibrosis and Remodeling
- Genomics and Chromatin Dynamics
- Endoplasmic Reticulum Stress and Disease
- Cardiovascular Function and Risk Factors
- Calpain Protease Function and Regulation
- Congenital heart defects research
- Microtubule and mitosis dynamics
- Cardiomyopathy and Myosin Studies
- Signaling Pathways in Disease
- Protease and Inhibitor Mechanisms
- Hepatitis Viruses Studies and Epidemiology
- Cellular Mechanics and Interactions
- Physiological and biochemical adaptations
- Williams Syndrome Research
- Galectins and Cancer Biology
- Gout, Hyperuricemia, Uric Acid
- Angiogenesis and VEGF in Cancer
- Cardiac Valve Diseases and Treatments
- Apelin-related biomedical research
- Epigenetics and DNA Methylation
- Healthcare and Venom Research
University of Turin
2005-2024
University of Copenhagen
2017-2024
Instituto de Salud Carlos III
2022
Universidad Autónoma de Madrid
2016
Albert Einstein College of Medicine
2016
Spanish National Centre for Cardiovascular Research
2014-2016
Institute of Genetics and Biophysics
2011
Istituto Neurologico Mediterraneo
2011
Sapienza University of Rome
2005
Technology Centre Prague
2005
The Notch signaling pathway is crucial for primitive cardiac valve formation by epithelial-mesenchymal transition, and NOTCH1 mutations cause bicuspid aortic valve; however, the temporal requirement various ligands receptors during ontogeny poorly understood.The aim of this study to determine functional specificity in development.Using cardiac-specific conditional targeted mutant mice, we find that endothelial/endocardial deletion Mib1-Dll4-Notch1 signaling, possibly favored Manic-Fringe,...
AimsThe Raf-MEK1/2-ERK1/2 (ERK1/2—extracellular signal-regulated kinases 1/2) signalling cascade is crucial in triggering cardiac responses to different stress stimuli. Scaffold proteins are key elements coordinating molecules for their appropriate spatiotemporal activation. Here, we investigated the role of IQ motif-containing GTPase-activating protein 1 (IQGAP1), a scaffold ERK1/2 cascade, heart function and remodelling response pressure overload.
Significance It has been reported that elevation of cGMP and activation cGMP-dependent protein kinase I (cGKI) by inhibition PDE5 activity with sildenafil prevents cardiac hypertrophy. We studied the roles cGKI on angiotensin (AII)-induced hypertrophy fibrosis using control (Ctr) mice expressing only in cells where smooth muscle SM22α promotor is active (βRM). In Ctr mice, did not reduce AII-induced increase cardiomyocyte (CM) size or myocyte hypertrophic markers but fibrosis. βRM had little...
We have previously shown that genetic ablation of melusin, a muscle specific beta 1 integrin interacting protein, accelerates left ventricle (LV) dilation and heart failure in response to pressure overload. Here we show melusin expression was increased during compensated cardiac hypertrophy mice subjected week overload, but returned basal levels LV undergone after 12 weeks To better understand the role remodeling, overexpressed transgenic mice. Echocardiography analysis indicated...
Heart failure is one of the leading causes mortality and primarily final stage several overload cardiomyopathies, preceded by an early adaptive hypertrophic response characterized coordinated cardiomyocyte growth, angiogenesis, inflammation. Therefore, growth factors cytokines have to be critically regulated during cardiac transverse aortic constriction. Interestingly, dual properties placental factor as angiogenic cytokine make it a candidate participate in remodeling hemodynamic...
To determine the role of NOTCH during arterial injury response and subsequent chronic arterial-wall inflammation underlying atherosclerosis.We have generated a mouse model endothelial-specific (Cdh5-driven) depletion Notch effector recombination signal binding protein for immunoglobulin kappa J region (RBPJ) [(ApoE-/-); homozygous RBPJk conditional mice (RBPJflox/flox); Cadherin 5-CreERT, tamoxifen inducible driver (Cdh5-CreERT)]. Endothelial-specific deletion RBPJ or systemic Notch1 in...
Extracellular signal-regulated kinase 1/2 (ERK1/2) signalling is a key pathway in cardiomyocyte hypertrophy and survival response to many different stress stimuli. We have previously characterized melusin as muscle-specific chaperone protein capable of ERK1/2 activation the heart. Here, we show that heart, forms supramolecular complex with proto-oncogene c-Raf, MEK1/2 (also known MAPKK1/2) melusin-bound mitogen-activated kinases (MAPKs) are activated by pressure overload. Moreover,...
Abstract Aims Melusin is a muscle-specific chaperone protein whose expression required for compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in setting myocardial infarction (MI) using comprehensive multicentre approach. Methods and results Mice overexpressing heart (TG) wild-type controls (WT) were subjected permanent LAD ligation both acute (Day 3) subsequent remodelling (2 weeks) examined. Mortality mice was significant...
Diabetes mellitus is a main risk factor for vascular diseases. Vascular injury induced by diabetes characterized endothelial dysfunction attributable to an increased oxidative stress. So far, the molecular mechanisms involved in vasculotoxic effects of are only partially known. We examined effect on stress and Rac-1 activation, small G-protein activation NADPH oxidase. Our results show that vessels different murine models cells treated with high glucose associated Rac-1/PAK binding...
The complex genetics underlying human cardiac disease is evidenced by its heterogenous manifestation, multigenic basis, and sporadic occurrence. These features have hampered modeling mechanistic understanding. Here, we show that 2 structural diseases, left ventricular noncompaction (LVNC) bicuspid aortic valve, can be caused a set of inherited heterozygous gene mutations affecting the NOTCH ligand regulator MIB1 (MINDBOMB1) cosegregating genes.
MINT‐6538515: melusin (Q9R000) physically interacts (MI:0218) with Hsp90 (P07901) by anti bait co-immunoprecipitation (MI:0006) MINT‐6538566, MINT‐6538556: cross-linking studies (MI:0030) MINT‐6538524: Sgt1 (Q9CS74) tag (MI:0007) MINT‐6538595: enzyme linked immunosorbent assay (MI:0411) MINT‐6538543: MINT‐6538580: surface plasmon resonance (MI:0107)
Maintenance of cardiac structure and Z-disc signaling are key factors responsible for protecting the heart in a setting stress, but how these processes regulated is not well defined. We recently demonstrated that PI3K(p110α) protects against myocardial infarction. The aim this study was to determine whether directly regulates components structure. To address question, unique three-dimensional virtual muscle model applied gene expression data from transgenic mice with increased or decreased...
PICH is a DNA translocase necessary for the resolution of ultrafine anaphase bridges and to ensure fidelity chromosomal segregation. Here, we report generation an animal model deficient that allowed us investigate its physiological relevance. Pich KO mice lose viability during embryonic development due global accumulation damage. However, despite presence instability, extensive p53 activation, increased apoptosis throughout embryo, embryos survive until day 12.5 development. The absence...
Abstract Plk1-interacting checkpoint helicase (PICH) is a DNA translocase involved in resolving ultrafine anaphase bridges and, therefore, important to safeguard chromosome segregation and stability. PICH overexpressed various human cancers, particularly lymphomas such as Burkitt lymphoma, which caused by MYC translocations. To investigate the relevance of cancer development progression, we have combined novel PICH-deficient mouse models with Eμ-Myc transgenic model, recapitulates B-cell...
Replication Stress (RS) is a type of DNA damage generated at the replication fork, characterized by single-stranded (ssDNA) accumulation, and which can be caused variety factors.Previous studies have reported elevated RS levels in aged cells.In addition, mouse models with deficient response show accelerated aging.However, relevance endogenous or physiological RS, compared to other sources genomic instability, for normal onset aging unknown.We performed long term survival transgenic mice...
Abstract Replication Stress (RS) is a type of DNA damage generated at the replication fork, characterized by single-stranded (ssDNA) accumulation, and which can be caused variety factors. Previous studies have reported elevated RS levels in aged cells. In addition, mouse models with deficient response show accelerated aging. However, relevance endogenous or physiological RS, compared to other sources genomic instability, for normal onset aging unknown. We performed long term survival...