Regulation of glycolysis by the hypoxia‐inducible factor (HIF): implications for cellular physiology

The Journal of Physiology, Journal Year: 2020, Volume and Issue: 599(1), P. 23 - 37

Published: Oct. 2, 2020

Under conditions of hypoxia, most eukaryotic cells can shift their primary metabolic strategy from predominantly mitochondrial respiration towards increased glycolysis to maintain ATP levels. This hypoxia-induced reprogramming metabolism is key satisfying cellular energetic requirements during acute hypoxic stress. At a transcriptional level, this switch be regulated by several pathways including the hypoxia inducible factor-1α (HIF-1α) which induces an expression glycolytic enzymes. While increase in flux beneficial for maintaining bioenergetic homeostasis mediating also exploited cancer promote tumour survival and growth, area has been extensively studied. It recently become appreciated that may have profound effects on physiology immune endothelial cells. Therefore, understanding mechanisms central are importance both physiological pathophysiological standpoints. In review, we highlight role HIF-1α regulation its implications processes such as angiogenesis cell effector function.

Language: Английский

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A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling

Cell Research, Journal Year: 2020, Volume and Issue: 30(9), P. 745 - 762

Published: June 19, 2020

Language: Английский

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Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(2), P. 1281 - 1324

Published: March 13, 2019

Numerous studies have demonstrated that endothelial cells are capable of undergoing to mesenchymal transition (EndMT), a newly recognized type cellular transdifferentiation. EndMT is complex biological process in which adopt phenotype displaying typical cell morphology and functions, including the acquisition motility contractile properties. Endothelial lose expression cell-specific proteins such as CD31/platelet-endothelial adhesion molecule, von Willebrand factor, vascular-endothelial cadherin initiate genes production their encoded α-smooth muscle actin, extra domain A fibronectin, N-cadherin, vimentin, fibroblast specific protein-1, also known S100A4 protein, fibrillar I III collagens. Transforming growth factor-β1 considered main inducer. However, involves numerous molecular signaling pathways triggered modulated by multiple often redundant mechanisms depending on context physiological or pathological status cells. participates highly important embryonic development processes, well pathogenesis genetically determined acquired human diseases malignant, vascular, inflammatory, fibrotic disorders. Despite intensive investigation, many aspects remain be elucidated. The identification molecules regulatory involved discovery inhibitors should provide novel therapeutic approaches for various disorders mediated EndMT.

Language: Английский

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Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases

Physiological Reviews, Journal Year: 2019, Volume and Issue: 100(1), P. 407 - 461

Published: Sept. 20, 2019

The formation and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis type 2 diabetes, vascular complications several other age-related chronic inflammatory diseases such as cardiovascular disease, cancer, disorders central nervous system. MGO is mainly formed byproduct glycolysis and, under physiological circumstances, detoxified by glyoxalase major precursor nonenzymatic glycation proteins DNA, subsequently leading to advanced end products (AGEs). MGO-derived AGEs can impact on organs tissues affecting their functions structure. In this review we summarize MGO, detoxification system, biochemical pathways through which linked development diseases. Although interventions treat MGO-associated are not yet available clinical setting, strategies lower have developed over years. We will new directions target stress including inducers scavengers. Targeting burden may provide therapeutic applications mitigate plays crucial role.

Language: Английский

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Basic and Therapeutic Aspects of Angiogenesis Updated

Circulation Research, Journal Year: 2020, Volume and Issue: 127(2), P. 310 - 329

Published: July 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.

Language: Английский

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Hallmarks of Endothelial Cell Metabolism in Health and Disease

Cell Metabolism, Journal Year: 2019, Volume and Issue: 30(3), P. 414 - 433

Published: Sept. 1, 2019

Language: Английский

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

Cell Metabolism, Journal Year: 2020, Volume and Issue: 31(4), P. 862 - 877.e14

Published: April 1, 2020

Language: Английский

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Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis

Cell Metabolism, Journal Year: 2018, Volume and Issue: 28(6), P. 881 - 894.e13

Published: Aug. 23, 2018

Language: Английский

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Mechanisms and consequences of endothelial cell senescence

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(1), P. 38 - 51

Published: July 19, 2022

Language: Английский

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Platelet Membrane Biomimetic Magnetic Nanocarriers for Targeted Delivery and in Situ Generation of Nitric Oxide in Early Ischemic Stroke

ACS Nano, Journal Year: 2020, Volume and Issue: 14(2), P. 2024 - 2035

Published: Jan. 13, 2020

Early diagnosis and treatment of acute ischemic stroke poses a significant challenge due to its suddenness short therapeutic time window. Human endogenous cells derived biomimetic drug carriers have provided new options for theranostics since these higher biosafety targeting abilities than artificial carriers. Inspired by natural platelets (PLTs) their role in adhesion the damaged blood vessel during thrombus formation, we fabricated nanocarrier comprising PLT membrane envelope loaded with l-arginine γ-Fe2O3 magnetic nanoparticles (PAMNs) thrombus-targeted delivery situ generation nitric oxide (NO). Results demonstrate that engineered 200 nm PAMNs inherit properties achieve rapid lesions under guidance an external field. Subsequent release at site, endothelial produce NO, which promotes vasodilation disrupt local aggregation. Rapid as well NO prompts vasodilation, recovery flow, reperfusion microvascular. Thus, nanocarriers are diagnostically beneficial localizing promising modality executing therapies.

Language: Английский

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