Basic and Therapeutic Aspects of Angiogenesis Updated

Circulation Research, Год журнала: 2020, Номер 127(2), С. 310 - 329

Опубликована: Июль 2, 2020

All organisms growing beyond the oxygen diffusion limit critically depend on a functional vasculature for survival. Yet blood vessels are far more than passive, uniform conduits and nutrient supply. A remarkable organotypic heterogeneity is brought about by tissue-specific differentiated endothelial cells (lining vessels’ lumen) allows to deal with organ-specific demands homeostasis. On flip side, when go awry, they promote life-threatening diseases characterized inappropriately adopting an angiogenic state (eg, tumor vascularization) or becoming dysfunctional diabetic microvasculopathies), calling respectively antiangiogenic therapies proangiogenic/vascular regenerative strategies. In solid tumors, despite initial enthusiasm, growth factor–based (mostly anti-VEGF [vascular factor]) do not sufficiently live up expectations in terms of efficiency patient survival, part, due intrinsic acquired therapy resistance. Tumors cunningly deploy alternative factors ones targeted reinstigate angiogenesis revert other ways securing flow, independently factors. trying alleviate tissue ischemia repair damaged endothelium, local in-tissue administration (genes encoding) proangiogenic (stem) harnessing potential have been explored. Notwithstanding evaluation clinical trials, these approaches often hampered dosing issues limited half-life retention administered agents. Here, without intending provide all-encompassing historical overview, we focus some recent advances understanding cell behavior health disease identify novel molecular players concepts that could eventually be considered therapeutic targeting.

Язык: Английский

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Hallmarks of Endothelial Cell Metabolism in Health and Disease

Cell Metabolism, Год журнала: 2019, Номер 30(3), С. 414 - 433

Опубликована: Сен. 1, 2019

Язык: Английский

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Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis

Cardiovascular Research, Год журнала: 2020, Номер 117(1), С. 29 - 42

Опубликована: Апрель 7, 2020

Abstract Endothelial cells (ECs) are sentinels of cardiovascular health. Their function is reduced by the presence risk factors, and regained once pathological stimuli removed. In this European Society for Cardiology Position Paper, we describe endothelial dysfunction as a spectrum phenotypic states advocate further studies to determine role EC subtypes in disease. We conclude that there no single ideal method measurement function. Techniques measure coronary epicardial micro-vascular well established but they invasive, time-consuming, expensive. Flow-mediated dilatation (FMD) brachial arteries provides non-invasive alternative technically challenging requires extensive training standardization. We, therefore, propose consensus methodology FMD universally adopted minimize technical variation between studies, reference values different populations healthy individuals patient groups. Newer techniques relatively easy perform, such finger plethysmography retinal flicker test, have potential increased clinical use provided achieved on protocol used. recommend establish these assess their ability improve stratification. future whether integration measurements with patient-specific epigenetic data other biomarkers can enhance stratification patients differential diagnosis, disease progression, responses therapy.

Язык: Английский

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Metabolism of vascular smooth muscle cells in vascular diseases

AJP Heart and Circulatory Physiology, Год журнала: 2020, Номер 319(3), С. H613 - H631

Опубликована: Авг. 7, 2020

Vascular smooth muscle cells (VSMCs) are the fundamental component of medial layer arteries and essential for arterial physiology pathology. It is becoming increasingly clear that VSMCs can alter their metabolism to fulfill bioenergetic biosynthetic requirements. During vascular injury, switch from a quiescent “contractile” phenotype highly migratory proliferative “synthetic” phenotype. Recent studies have found switching driven by metabolic switch. Metabolic pathways, including aerobic glycolysis, fatty acid oxidation, amino metabolism, distinct, indispensable roles in normal dysfunctional vasculature. also related endothelial cells. In present review, we brief overview how it regulates progression several diseases, atherosclerosis, systemic hypertension, diabetes, pulmonary calcification, aneurysms, effect risk factors disease (aging, cigarette smoking, excessive alcohol drinking) on VSMC clarify role key pathological process.

Язык: Английский

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Single-Cell RNA Sequencing Maps Endothelial Metabolic Plasticity in Pathological Angiogenesis

Cell Metabolism, Год журнала: 2020, Номер 31(4), С. 862 - 877.e14

Опубликована: Апрель 1, 2020

Язык: Английский

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Autophagy in endothelial cells and tumor angiogenesis

Cell Death and Differentiation, Год журнала: 2019, Номер 26(4), С. 665 - 679

Опубликована: Янв. 28, 2019

In mammalian cells, autophagy is the major pathway for degradation and recycling of obsolete potentially noxious cytoplasmic materials, including proteins, lipids, whole organelles, through lysosomes. Autophagy maintains cellular tissue homeostasis provides a mechanism to adapt extracellular cues metabolic stressors. Emerging evidence unravels critical function in endothelial cells (ECs), components blood vasculature, which delivers nutrients oxygen parenchymal tissue. EC-intrinsic modulates response ECs various stressors has fundamental role redox EC plasticity. recent years moreover, genetic suggests that regulates pathological angiogenesis, hallmark solid tumors. hypoxic, nutrient-deprived, pro-angiogenic tumor microenvironment, heightened vessels emerging as enabling dynamically accommodate their higher bioenergetics demands environment connect with other stroma paracrine signaling. this review, we provide an overview mechanisms regulated by discuss potential growth, anticancer therapy.

Язык: Английский

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Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity

Circulation Research, Год журнала: 2020, Номер 127(4), С. 466 - 482

Опубликована: Май 14, 2020

Endothelial cells (ECs) are highly glycolytic and generate the majority of their energy via breakdown glucose to lactate. At same time, a main role ECs is allow transport surrounding tissues. GLUT1 (glucose transporter isoform 1/Slc2a1) expressed in central nervous system (CNS) often implicated blood-brain barrier (BBB) dysfunction, but whether how controls EC metabolism function poorly understood.We evaluated endothelial during postnatal CNS development as well at adult BBB.Inhibition decreases uptake glycolysis, leading depletion activation cellular sensor AMPK (AMP-activated protein kinase), proliferation without affecting migration. Deletion from developing retinal endothelium reduces lowers vascular outgrowth, number tip cells. In contrast, brain, we observed lower addition reduced brain proliferation, indicating that within CNS, organotypic differences exist. Interestingly, when become quiescent, glycolysis repressed, expression increases Notch-dependent fashion. deletion quiescent leads severe seizures, accompanied by neuronal loss inflammation. Strikingly, this does not coincide with BBB leakiness, altered genes crucial for functioning nor function. Instead, found selective inflammatory extracellular matrix related gene sets.GLUT1 becomes uncoupled quiescence manner. It developmental angiogenesis homeostasis affect

Язык: Английский

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Serine Catabolism Feeds NADH when Respiration Is Impaired

Cell Metabolism, Год журнала: 2020, Номер 31(4), С. 809 - 821.e6

Опубликована: Март 17, 2020

Язык: Английский

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Angiogenesis in Adipose Tissue: The Interplay Between Adipose and Endothelial Cells

Frontiers in Physiology, Год журнала: 2021, Номер 11

Опубликована: Фев. 9, 2021

Obesity is a worldwide health problem, and as its prevalence increases, so does the burden of obesity-associated co-morbidities like type 2 diabetes or cardiovascular diseases (CVDs). Adipose tissue (AT) an endocrine organ embedded in dense vascular network. AT regulates production hormones, angiogenic factors, cytokines. During development obesity, expands through increase fat cell size (hypertrophy) and/or number (hyperplasia). The plasticity expansion related to capacities. Angiogenesis tightly orchestrated process, which involves endothelial (EC) proliferation, migration, invasion, new tube formation. accelerated by hypoxia, inflammation, structural remodeling blood vessels. paracrine signaling functional link between ECs adipocytes. Adipocytes can secrete both pro-angiogenic molecules, e.g., tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), growth factor (VEGF), anti-angiogenic serpins. If molecules dominate, angiogenesis dysregulated endothelium becomes dysfunctional. However, if are overexpressed relative regulators, repressed, hypoxic. Furthermore, presence chronic nutritional excess, loses primary function contributes inflammation fibrosis AT, increases risk for CVDs. This review discusses current understanding cross-talk adipose ECs, how obesity lead dysfunction. Understanding interplay with be approach therapy obesity-related such

Язык: Английский

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A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling

Nature Cancer, Год журнала: 2023, Номер 4(3), С. 344 - 364

Опубликована: Фев. 2, 2023

Язык: Английский

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