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614 results match your criteria: "Wihuri Research Institute[Affiliation]"
Nat Commun
September 2023
Translational Cancer Medicine Research Program, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland.
Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient data indicate that the lymphatic capillary density directly correlates with functional output, i.
View Article and Find Full Text PDFAnn Rheum Dis
November 2023
Translational Matrix Biology, University of Cologne, Cologne, Germany
Objectives: Activation of fibroblasts is a hallmark of fibrotic processes. Besides cytokines and growth factors, fibroblasts are regulated by the extracellular matrix environment through receptors such as integrins, which transduce biochemical and mechanical signals enabling cells to mount appropriate responses according to biological demands. The aim of this work was to investigate the in vivo role of collagen-fibroblast interactions for regulating fibroblast functions and fibrosis.
View Article and Find Full Text PDFNat Cardiovasc Res
March 2023
Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Leukocytes and resident cells in the arterial wall contribute to atherosclerosis, especially at sites of disturbed blood flow. Expression of endothelial Tie1 receptor tyrosine kinase is enhanced at these sites, and attenuation of its expression reduces atherosclerotic burden and decreases inflammation. However, Tie2 tyrosine kinase function in atherosclerosis is unknown.
View Article and Find Full Text PDFCirc Res
August 2023
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China (X.C., X. Zhou, L.Z., W.L., X. Zhang, Y.L., W.Z., K.L., R.J., X.L., F.Z.).
Background: Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas closed junctions in collecting LECs prevent lymph leakage. LEC junctions are known to dynamically remodel in development and disease, but how lymphatic permeability is regulated remains poorly understood.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
August 2023
Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Cam-Su Genomic Resources Center, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China (X.C., T.L., B.X., K.D., B.S., M.C., D.Z., L.R., Z.S., X.L., Y.H.).
Background: Vascular growth followed by vessel specification is crucial for the establishment of a hierarchical blood vascular network. We have shown that TIE2 is required for vein development while little is known about its homologue TIE1 (tyrosine kinase with immunoglobulin-like and EGF [epithelial growth factor]-like domains 1) in this process.
Methods: We analyzed functions of TIE1 as well as its synergy with TIE2 in the regulation of vein formation by employing genetic mouse models targeting , , and , together with in vitro cultured endothelial cells to decipher the underlying mechanism.
Atheroscler Plus
September 2023
Mehiläinen, Airport Health Center, Vantaa, Finland.
In this short narrative review, we aim at defining the pathophysiological role endothelial dysfunction in the observed COVID-19-associated rise in risk of cardiovascular disease. Variants of the SARS-CoV-2 virus have caused several epidemic waves of COVID-19, and the emergence and rapid spread of new variants and subvariants are likely. Based on a large cohort study, the incidence rate of SARS-CoV-2 reinfection is about 0.
View Article and Find Full Text PDFFront Cardiovasc Med
May 2023
Atherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland.
Introduction: Lipoprotein(a) (Lp(a)) is an LDL-like particle with an additional apolipoprotein (apo)(a) covalently attached. Elevated levels of circulating Lp(a) are a risk factor for atherosclerosis. A proinflammatory role for Lp(a) has been proposed, but its molecular details are incompletely defined.
View Article and Find Full Text PDFAtherosclerosis
July 2023
Heart and Lung Center, Cardiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. Electronic address:
Lowering elevated low-density lipoprotein cholesterol (LDL-C) concentrations reduces the risk of atherosclerotic cardiovascular diseases (ASCVDs). However, increasing evidence suggests that cholesterol metabolism may also be involved in the risk reduction of ASCVD events. In this review, we discuss if the different profiles of cholesterol metabolism, with a focus on high cholesterol absorption, are atherogenic, and what could be the possible mechanisms.
View Article and Find Full Text PDFSTAR Protoc
May 2023
Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki 00014, Finland; Wihuri Research Institute, Helsinki 00290, Finland. Electronic address:
The small intestine is an excellent model for studying changes in vasculature in response to different diseases or gene deletions. Here, we present a protocol for whole-mount immunofluorescence staining of blood and lymphatic vessels in the adult mouse small intestine. We describe the steps for perfusion fixation, tissue sample preparation, immunofluorescence staining, and whole-mount preparation of stained samples.
View Article and Find Full Text PDFNutr Metab Cardiovasc Dis
July 2023
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland.
Background And Aims: Lipophilic index (LI) has been introduced to assess the overall fatty acid lipophilicity and as a simple estimate of membrane fluidity. However, little is known on effect of diet on LI. We tested if Camelina sativa oil (CSO) high in ALA, fatty fish (FF) or lean fish (LF) affect LI as compared to control diet and, secondarily, if the LI is associated with HDL lipids and functionality and LDL lipidome.
View Article and Find Full Text PDFSemin Cancer Biol
August 2023
Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain. Electronic address:
Obesity has been closely related to cancer progression, recurrence, metastasis, and treatment resistance. We aim to review recent progress in the knowledge on the obese macroenvironment and the generated adipose tumor microenvironment (TME) inducing lipid metabolic dysregulation and their influence on carcinogenic processes. Visceral white adipose tissue expansion during obesity exerts systemic or macroenvironmental effects on tumor initiation, growth, and invasion by promoting inflammation, hyperinsulinemia, growth-factor release, and dyslipidemia.
View Article and Find Full Text PDFVaccine
May 2023
Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Diagnostic Center, Helsinki University Hospital, Helsinki, Finland. Electronic address:
The ongoing SARS-CoV-2 pandemic is controlled but not halted by public health measures and mass vaccination strategies which have exclusively relied on intramuscular vaccines. Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing infection. Here we report a comprehensive series of studies on this concept using various mouse models, including HLA class II-humanized transgenic strains.
View Article and Find Full Text PDFAnn Med
December 2023
Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
Patients with hypercholesterolemia often have coronary microvascular dysfunction (CMD). Viral infections, such as the SARS-CoV-2 infection, may also result in CMD. Three non-randomized studies have shown significant beneficial effects of statins on CMD in non-infected patients.
View Article and Find Full Text PDFSci Immunol
April 2023
Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
The recent discovery of lymphatic vessels (LVs) in the dura mater, the outermost layer of meninges around the central nervous system (CNS), has opened a possibility for the development of alternative therapeutics for CNS disorders. The vascular endothelial growth factor C (VEGF-C)/VEGF receptor 3 (VEGFR3) signaling pathway is essential for the development and maintenance of dural LVs. However, its significance in mediating dural lymphatic function in CNS autoimmunity is unclear.
View Article and Find Full Text PDFAngiogenesis
August 2023
Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Biocenter 2, (Viikinkaari 5E), P.O. Box. 56, 00790, Helsinki, Finland.
Together with the platelet-derived growth factors (PDGFs), the vascular endothelial growth factors (VEGFs) form the PDGF/VEGF subgroup among cystine knot growth factors. The evolutionary relationships within this subgroup have not been examined thoroughly to date. Here, we comprehensively analyze the PDGF/VEGF growth factors throughout all animal phyla and propose a phylogenetic tree.
View Article and Find Full Text PDFNat Commun
April 2023
Experimental Medicine and Clinical Pathology Unit, Department of Clinical and Biological Sciences, University of Torino, Turin, Italy.
Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD) loss to associate with muscle mitochondrial dysfunction in cancer hosts.
View Article and Find Full Text PDFEMBO Rep
May 2023
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
The growth factor Neuregulin-1 (NRG-1) regulates myocardial growth and is currently under clinical investigation as a treatment for heart failure. Here, we demonstrate in several in vitro and in vivo models that STAT5b mediates NRG-1/EBBB4-stimulated cardiomyocyte growth. Genetic and chemical disruption of the NRG-1/ERBB4 pathway reduces STAT5b activation and transcription of STAT5b target genes Igf1, Myc, and Cdkn1a in murine cardiomyocytes.
View Article and Find Full Text PDFEur J Cell Biol
June 2023
EV group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and CURED, Drug Research Program, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, University of Helsinki, Helsinki, Finland; EV Core, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland. Electronic address:
Platelet extracellular vesicles (PEVs) generated upon platelet activation may play a role in inflammatory pathologies such as atherosclerosis. Oxidized low-density lipoprotein (oxLDL), a well-known contributor to atherogenesis, activates platelets and presensitizes them for activation by other agonists. We studied the effect of oxLDL on the secretion, composition, and inflammatory functions of PEVs using contemporary EV analytics.
View Article and Find Full Text PDFCardiovasc Res
July 2023
Department of Biomedicine, University of Bergen, Jonas Leis vei 91, 5020 Bergen, Norway.
Aims: Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of the metabolic alterations is complex and likely dependent on the particular stage of HF progression. Vascular endothelial growth factor B (VEGF-B) has been shown to modulate metabolic processes and to induce physiological cardiac hypertrophy; thus, it could be cardioprotective in the failing myocardium. This study investigates the role of VEGF-B in cardiac proteomic and metabolic adaptation in HF during aldosterone and high-salt hypertensive challenges.
View Article and Find Full Text PDFCurr Opin Lipidol
June 2023
Wihuri Research Institute, Atherosclerosis Research Laboratory, Helsinki, Finland.
Purpose Of Review: Patients with heterozygous familial hypercholesterolemia (HeFH) are at increased risk for COVID-19 cardiovascular complications in the acute phase of the infection. Elevated levels of LDL-C and often lipoprotein(a) are present from birth and lead to endothelial dysfunction, which is aggravated by a direct viral attack of the endothelial cells and their exposure to the toxic levels of circulating proinflammatory and prothrombotic mediators during the hyperinflammatory reaction typical of COVID-19.
Recent Findings: Evidence to date shows the benefit of lipid-lowering therapy in patients with COVID-19.
J Infect
May 2023
Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:
EMBO J
March 2023
The Centenary Institute, David Richmond Program for Cardio-Vascular Research: Gene Regulation and Editing, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
Despite a growing catalog of secreted factors critical for lymphatic network assembly, little is known about the mechanisms that modulate the expression level of these molecular cues in blood vascular endothelial cells (BECs). Here, we show that a BEC-specific transcription factor, SOX7, plays a crucial role in a non-cell-autonomous manner by modulating the transcription of angiocrine signals to pattern lymphatic vessels. While SOX7 is not expressed in lymphatic endothelial cells (LECs), the conditional loss of SOX7 function in mouse embryos causes a dysmorphic dermal lymphatic phenotype.
View Article and Find Full Text PDFPLoS Pathog
January 2023
Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Kaposi's sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a hyperplasia consisting of enlarged malformed vasculature and spindle-shaped cells, the main proliferative component of KS. While spindle cells express markers of lymphatic and blood endothelium, the origin of spindle cells is unknown. Endothelial precursor cells have been proposed as the source of spindle cells.
View Article and Find Full Text PDFNat Med
January 2023
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Little is known about the genetic determinants of medication use in preventing cardiometabolic diseases. Using the Finnish nationwide drug purchase registry with follow-up since 1995, we performed genome-wide association analyses of longitudinal patterns of medication use in hyperlipidemia, hypertension and type 2 diabetes in up to 193,933 individuals (55% women) in the FinnGen study. In meta-analyses of up to 567,671 individuals combining FinnGen with the Estonian Biobank and the UK Biobank, we discovered 333 independent loci (P < 5 × 10) associated with medication use.
View Article and Find Full Text PDFRev Cardiovasc Med
December 2022
Wihuri Research Institute, 00290 Helsinki, Finland.
Heterozygous familial hypercholesterolemia (HeFH) patients are the prime example of subjects who are at high risk for both acute myocardial infarction (AMI) and ischemic stroke during, and post, SARS-CoV-2 infection. HeFH , if left untreated, results in premature clinical atherosclerosis often presenting in the fourth or fifth decade of life. The other concern in HeFH is endothelial dysfunction which is already evident from early childhood.
View Article and Find Full Text PDF