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Angiogenesis 2022 May 11. Epub 2022 May 11.

Department of Oncology, University of Torino, Candiolo, Italy.

The dynamic integrin-mediated adhesion of endothelial cells (ECs) to the surrounding ECM is fundamental for angiogenesis both in physiological and pathological conditions, such as embryonic development and cancer progression. The dynamics of EC-to-ECM adhesions relies on the regulation of the conformational activation and trafficking of integrins. Here, we reveal that oncogenic transcription factor EB (TFEB), a known regulator of lysosomal biogenesis and metabolism, also controls a transcriptional program that influences the turnover of ECM adhesions in ECs by regulating cholesterol metabolism. Read More

Angiogenesis 2022 May 3. Epub 2022 May 3.

Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, No. 99, Huaihai West Road, Xuzhou, 221002, Jiangsu, China.

Angiogenesis is an essential factor affecting the occurrence and development of solid tumors. SET And MYND Domain Containing 2 (SMYD2) serves as an oncogene in various cancers. However, whether SMYD2 is involved in tumor angiogenesis remains unclear. Read More

Angiogenesis 2022 Apr 21. Epub 2022 Apr 21.

Department of Biological Sciences, University of Denver, Denver, CO, 80210, USA.

Blood vessels demonstrate a multitude of complex signaling programs that work in concert to produce functional vasculature networks during development. A known, but less widely studied, area of endothelial cell regulation is vesicular trafficking, also termed sorting. After moving through the Golgi apparatus, proteins are shuttled to organelles, plugged into membranes, recycled, or degraded depending on the internal and extrinsic cues. Read More

Angiogenesis 2022 Apr 13. Epub 2022 Apr 13.

UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.

Blood vessels form vast networks in all vertebrate organs to sustain tissue growth, repair and homeostatic metabolism, but they also contribute to a range of diseases with neovascularisation. It is, therefore, important to define the molecular mechanisms that underpin blood vessel growth. The receptor tyrosine kinase KIT is required for the normal expansion of hematopoietic progenitors that arise during embryogenesis from hemogenic endothelium in the yolk sac and dorsal aorta. Read More

Angiogenesis 2022 Apr 7. Epub 2022 Apr 7.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Somatic mutations in NRAS drive the pathogenesis of melanoma and other cancers but their role in vascular anomalies and specifically human endothelial cells is unclear. The goals of this study were to determine whether the somatic-activating NRAS mutation in human endothelial cells induces abnormal angiogenesis and to develop in vitro and in vivo models to identify disease-causing pathways and test inhibitors. Here, we used mutant NRAS and wild-type NRAS (NRAS) expressing human endothelial cells in in vitro and in vivo angiogenesis models. Read More

Angiogenesis 2022 Mar 23. Epub 2022 Mar 23.

Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, 6 Center Dr. Bethesda, Bethesda, MD, 20892, USA.

The small monomeric GTPase RHOA acts as a master regulator of signal transduction cascades by activating effectors of cellular signaling, including the Rho-associated protein kinases ROCK1/2. Previous in vitro cell culture studies suggest that RHOA can regulate many critical aspects of vascular endothelial cell (EC) biology, including focal adhesion, stress fiber formation, and angiogenesis. However, the specific in vivo roles of RHOA during vascular development and homeostasis are still not well understood. Read More

Angiogenesis 2022 Mar 18. Epub 2022 Mar 18.

Senior Department of Cardiology, The Sixth Medical Center of People's Liberation Army General Hospital, Beijing, China.

Coronary microvascular endothelial dysfunction is both a culprit and a victim of diabetes, and can accelerate diabetes-related microvascular and macrovascular complications by promoting vasoconstrictive, pro-inflammatory and pro-thrombotic responses. Perturbed mitochondrial function induces oxidative stress, disrupts metabolism and activates apoptosis in endothelial cells, thus exacerbating the progression of coronary microvascular complications in diabetes. The mitochondrial quality surveillance (MQS) system responds to stress by altering mitochondrial metabolism, dynamics (fission and fusion), mitophagy and biogenesis. Read More

Angiogenesis 2022 Feb 25. Epub 2022 Feb 25.

Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, 11.211 Karp Family Research Bldg., 300 Longwood Ave., Boston, MA, 02115, USA.

Anthrax protective antigen (PA) is a potent inhibitor of pathological angiogenesis with an unknown mechanism. In anthrax intoxication, PA interacts with capillary morphogenesis gene 2 (CMG2) and tumor endothelial marker 8 (TEM8). Here, we show that CMG2 mediates the antiangiogenic effects of PA and is required for growth-factor-induced chemotaxis. Read More

Angiogenesis 2022 Feb 14. Epub 2022 Feb 14.

Department of Trauma and Reconstructive Surgery, BG Trauma Center Tuebingen, Eberhard Karls University Tuebingen, 72076, Tuebingen, Germany.

Despite major research efforts to elucidate mechanisms of non-union formation, failed fracture healing remains a common complication in orthopedic surgery. Adequate vascularization has been recognized as a crucial factor for successful bone regeneration, as newly formed microvessels guarantee the supply of the callus tissue with vital oxygen, nutrients, and growth factors. Accordingly, a vast number of preclinical studies have focused on the development of vascularization strategies to stimulate fracture repair. Read More

Angiogenesis 2022 Feb 3. Epub 2022 Feb 3.

Department of Developmental Biology and Cancer Research, Faculty of Medicine, Hadassah Medical School, The Hebrew University, 9112001, Jerusalem, Israel.

Glioblastoma stem cells (GSCs) reside close to blood vessels (BVs) but vascular cues contributing to GSC stemness and the nature of GSC-BVs cross talk are not fully understood. Here, we dissected vascular cues influencing GSC gene expression and function to perfusion-based vascular cues, as well as to those requiring direct GSC-endothelial cell (EC) contacts. In light of our previous finding that perivascular tumor cells are metabolically different from tumor cells residing further downstream, cancer cells residing within a narrow, < 60 µm wide perivascular niche were isolated and confirmed to possess a superior tumor-initiation potential compared with those residing further downstream. Read More

Angiogenesis 2022 Feb 1. Epub 2022 Feb 1.

Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1406 S. Coulter St., Amarillo, TX, 79106, USA.

Lymphangiogenesis is an essential physiological process but also a determining factor in vascular-related pathological conditions. Angiopoietin-2 (Ang2) plays an important role in lymphatic vascular development and function and its upregulation has been reported in several vascular-related diseases, including cancer. Given the established role of the small GTPase RhoA on cytoskeleton-dependent endothelial functions, we investigated the relationship between RhoA and Ang2-induced cellular activities. Read More

Angiogenesis 2022 May 31;25(2):155-158. Epub 2022 Jan 31.

Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona and Bellvitge Biomedical Research Institute, L'Hospitalet del Llobregat, 08907, Barcelona, Spain.

Alpha-parvin (α-pv), an adaptor protein that mediates integrin-dependent cell-matrix interactions, is essential for endothelial cells migration and proliferation and is a key player in physiological angiogenesis. The role of α-pv in pathological angiogenesis is unknown. Here we demonstrate that endothelial α-pv is required for tumour angiogenesis. Read More

Angiogenesis 2022 May 16;25(2):241-257. Epub 2022 Jan 16.

College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, China.

Molecular transport and cell circulation between tissues and organs through blood and lymphatic vessels are essential for physiological homeostasis in vertebrates. Despite the report of its association with vessel formation in solid tumors, the biological effects of Copper (Cu) accumulation on angiogenesis and lymphangiogenesis during embryogenesis are still unknown. In this study, we unveiled that intersegmental blood circulation was partially blocked in Cu-stressed zebrafish embryos and cell migration and tube formation were impaired in Cu-stressed mammalian HUVECs. Read More

Angiogenesis 2022 Jan 11. Epub 2022 Jan 11.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, F-75006, Paris, France.

Chronic obstructive pulmonary disease (COPD) patients have an increased risk of cardiovascular disease. Muscle biopsies have revealed that the muscle vasculature in COPD patients was characterized by a capillary rarefaction with reduced pericyte coverage. Thus, an imbalance of the plasma Angiopoietin-1 / Angiopoietin-2 (Ang2/Ang1) ratio could constitute a non-invasive marker of the muscle vascular impairment. Read More

Angiogenesis 2022 May 8;25(2):259-274. Epub 2022 Jan 8.

Oulu Centre for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.

Hypoxia plays an important regulatory role in the vasculature to adjust blood flow to meet metabolic requirements. At the level of gene transcription, the responses are mediated by hypoxia-inducible factor (HIF) the stability of which is controlled by the HIF prolyl 4-hydroxylase-2 (PHD2). In the lungs hypoxia results in vasoconstriction, however, the pathophysiological relevance of PHD2 in the major arterial cell types; endothelial cells (ECs) and arterial smooth muscle cells (aSMCs) in the adult vasculature is incompletely characterized. Read More

Angiogenesis 2022 02;25(1):1-3

Biological Sciences Platform, Department of Medical Biophysics, Sunnybrook Research Institute, University of Toronto, Toronto, Canada.

Angiogenesis 2022 02 14;25(1):35-45. Epub 2021 Dec 14.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Physiology, Berlin, Germany.

Angiogenesis describes the formation of new blood vessels from pre-existing vascular structures. While the most studied mode of angiogenesis is vascular sprouting, specific conditions or organs favor intussusception, i.e. Read More

Angiogenesis 2022 May 29;25(2):225-240. Epub 2021 Oct 29.

Division of Pulmonary Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.

Severe viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a hyperinflammatory state typified by elevated circulating pro-inflammatory cytokines, frequently leading to potentially lethal vascular complications including thromboembolism, disseminated intracellular coagulopathy and vasculitis. Though endothelial infection and subsequent endothelial damage have been described in patients with fatal COVID-19, the mechanism by which this occurs remains elusive, particularly given that, under naïve conditions, pulmonary endothelial cells demonstrate minimal cell surface expression of the SARS-CoV-2 binding receptor ACE2. Herein we describe SARS-CoV-2 infection of the pulmonary endothelium in postmortem lung samples from individuals who died of COVID-19, demonstrating both heterogeneous ACE2 expression and endothelial damage. Read More

Angiogenesis 2022 May 19;25(2):205-224. Epub 2021 Oct 19.

Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, 10032, USA.

In mice, embryonic dermal lymphatic development is well understood and used to study gene functions in lymphangiogenesis. Notch signaling is an evolutionarily conserved pathway that modulates cell fate decisions, which has been shown to both inhibit and promote dermal lymphangiogenesis. Here, we demonstrate distinct roles for Notch4 signaling versus canonical Notch signaling in embryonic dermal lymphangiogenesis. Read More

Angiogenesis 2022 May 6;25(2):151-154. Epub 2021 Oct 6.

Shiseido Global Innovation Center, 1-2-11, Takashima, Nishi-ku, Yokohama, 220-0011, Japan.

Microvascular dysfunction accompanied by a dramatic alteration of stable capillary structure is a major hallmark of numerous age-related diseases. In skin, although the role of angiogenesis during dermal reconstitution is well documented, the functional relevance of the extracellular matrix (ECM) stiffness to vascular remodeling and its molecular mechanisms was poorly understood. Here, we developed an ex vivo 3-dimensional angiogenic model using human fat, revealing that "appropriate" stiffness induces vascular maturation associated with upregulated APJ expression, whereas the overexpression of APJ promotes the formation of large vessels even in the absence of the "appropriate" stiffness. Read More

Angiogenesis 2022 May 6;25(2):181-203. Epub 2021 Oct 6.

Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 1/F, Professorial Block, 102 Pokfulam Road, Pok Fu Lam, Hong Kong.

Several B-cell subsets with distinct functions and polarized cytokine profiles that extend beyond antibody production have been reported in different cancers. Here we have demonstrated that proliferating B cells were predominantly found in the peritumoral region of esophageal squamous cell carcinoma (ESCC). These B cells were enriched in tumor nests with high expression of high-mobility group box 1 (HMGB1). Read More

Angiogenesis 2022 May 30;25(2):147-149. Epub 2021 Sep 30.

Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

We report a unique case of advanced non-small cell lung cancer that exhibited the opposite response to its unilateral choroidal metastases upon ramucirumab plus docetaxel treatment. A combination of cisplatin, pemetrexed, and pembrolizumab was administered as first-line treatment, resulting in shrinkage of all the lesions. However, although the patient was continued on a course of pembrolizumab, all the lesions had recurred approximately two months later. Read More

Angiogenesis 2022 May 15;25(2):159-179. Epub 2021 Sep 15.

WELBIO and I.R.I.B.H.M, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070, Brussels, Belgium.

Chemerin is a multifunctional protein initially characterized in our laboratory as a chemoattractant factor for leukocyte populations. Its main functional receptor is CMKLR1. We identified previously chemerin as an anti-tumoral factor inhibiting the vascularization of tumor grafts. Read More

Angiogenesis 2022 02 9;25(1):15-33. Epub 2021 Sep 9.

The University of Queensland Diamantina Institute, 37 Kent Street, Woolloongabba, Brisbane, 4102, Australia.

The cardiovascular system is composed around the central function of the endothelium that lines the inner surfaces of its vessels. In recent years, the existence of a progenitor population within the endothelium has been validated through the study of endothelial colony-forming cells (ECFCs) in human peripheral blood and certain vascular beds. However, our knowledge on endothelial populations in vivo that can give rise to ECFCs in culture has been limited. Read More

Angiogenesis 2022 02 3;25(1):113-128. Epub 2021 Sep 3.

Department of Oncology, University of Turin, Candiolo, Italy.

Embryonic stem cells (ES) are a valuable source of endothelial cells. By co-culturing ES cells with the stromal PA6 cells, the endothelial commitment can be achieved by adding exogenous FGF2 or BMP4. In this work, the molecular pathways that direct the differentiation of ES cells toward endothelium in response to FGF2 are evaluated and compared to those activated by BMP4. Read More

Angiogenesis 2022 02 25;25(1):129-143. Epub 2021 Aug 25.

Laboratory of Physiopharmacology, University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium.

Vein grafting is a frequently used surgical intervention for cardiac revascularization. However, vein grafts display regions with intraplaque (IP) angiogenesis, which promotes atherogenesis and formation of unstable plaques. Graft neovessels are mainly composed of endothelial cells (ECs) that largely depend on glycolysis for migration and proliferation. Read More

Angiogenesis 2022 02 18;25(1):13-14. Epub 2021 Aug 18.

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Angiogenesis 2022 02 14;25(1):9-11. Epub 2021 Aug 14.

Department of Pharmacy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Road, Xindian Dist, New Taipei City, 23142, Taiwan, Republic of China.

Systemic capillary leak syndrome (SCLS) is a syndrome caused by many reasons and without a definitive mechanism. The main diagnostic criteria of SCLS are hemoconcentration, hypoalbuminemia, and hypotension. Though most SCLS improved spontaneously within a few days, it can be life-threatening without effective treatments. Read More

Angiogenesis 2022 02 11;25(1):99-112. Epub 2021 Aug 11.

Department of Paediatric Cardiology, Beatrix Children's Hospital, Center for Congenital Heart Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Pulmonary arterial hypertension (PAH) is a devastating disease, characterized by obstructive pulmonary vascular remodelling ultimately leading to right ventricular (RV) failure and death. Disturbed transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) signalling, endothelial cell dysfunction, increased proliferation of smooth muscle cells and fibroblasts, and inflammation contribute to this abnormal remodelling. Peptidyl-prolyl isomerase Pin1 has been identified as a critical driver of proliferation and inflammation in vascular cells, but its role in the disturbed TGF-β/BMP signalling, endothelial cell dysfunction, and vascular remodelling in PAH is unknown. Read More

Angiogenesis 2022 Feb;25(1):145

Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands.