The role of vasculature and angiogenesis in respiratory diseases

Ackermann, Maximilian; Werlein, Christopher; Plucinski, Edith; Leypold, Sophie; Kühnel, Mark P.; Verleden, Stijn E.; Khalil, Hassan A.; Länger, Florian; Welte, Tobias; Mentzer, Steven J.; Jonigk, Danny D.

doi:10.1007/s10456-024-09910-2

Cited by 7 publications

(2 citation statements)

References 180 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This subsequently allows ECs to invade and disintegrate the surrounding matrix, proliferate, form new immature blood vessels, and, therefore, develop a more extensive network for the nourishment of the growing tumor [20] . Vascular endothelial growth factor (VEGF) is a widely expressed angiogenic growth factor and plays a crucial role in sprouting angiogenesis, as well as angiogenesis in general, by inducing EC proliferation and migration, mainly through filopodia tip cell formation [21] . Hypoxia also represents a potent inducer of sprouting angiogenesis and reveals its potential for tumor promotion as the unbridled growth of cancer causes ubiquitous hypoxic conditions [22] .…”

Section: Tumor Angiogenesis In Hnsccmentioning

confidence: 99%

Anti-angiogenic therapy in head and neck squamous cell carcinoma - current limitations and future directions

Nieberle,

Spoerl,

Głuszko

et al. 2024

Vessel Plus

View full text Add to dashboard Cite

Angiogenesis, the formation of new blood vessels, plays a crucial role in the progression and metastasis of various cancers, including head and neck squamous cell carcinoma (HNSCC). HNSCCs are characterized by altered levels of angiogenesis-related factors, including the overexpression of pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), as well as the dysregulation of angiogenesis inhibitors. Together, these factors drive the formation of new blood vessels within the tumor microenvironment and are considered therapeutic targets in HNSCC. Although preclinical studies are promising, challenges have emerged in the clinical use of anti-angiogenic agents in the clinic, including treatment-related toxicities and the development of resistance to therapy. There is an unmet need for further research to elucidate the molecular pathways involved in HNSCC angiogenesis, identify novel therapeutic targets, and discover predictive biomarkers to improve patient selection.

show abstract

Section: Tumor Angiogenesis In Hnsccmentioning

confidence: 99%

Anti-angiogenic therapy in head and neck squamous cell carcinoma - current limitations and future directions

Nieberle,

Spoerl,

Głuszko

et al. 2024

Vessel Plus

View full text Add to dashboard Cite

show abstract

“…Endothelial cells of different organs must fulfill a variety of tissue-specific functions, such as maintenance of the blood-brain barrier (BBB), support of metabolic processes in the liver, gas exchange in the lung, or blood ultrafiltration in the kidneys [31][32][33][34][35][36][37][38]. This specificity of endothelial cells is achieved by the formation of specialized morphological structures and their underlying gene expression patterns [39][40][41][42].…”

Section: Vascular Homeostasis In Bonementioning

confidence: 99%

Exosomes: A New Hope for Angiogenesis-Mediated Bone Regeneration

Lange,

Babczyk,

Tobiasch

2024

IJMS

View full text Add to dashboard Cite

Bone is a metabolically dynamic structure that is generally remodeled throughout the lifetime of an individual but often causes problems with increasing age. A key player for bone development and homeostasis, but also under pathological conditions, is the bone vasculature. This complex system of arteries, veins, and capillaries forms distinct structures where each subset of endothelial cells has important functions. Starting with the basic process of angiogenesis and bone-specific blood vessel formation, coupled with initial bone formation, the importance of different vascular structures is highlighted with respect to how these structures are maintained or changed during homeostasis, aging, and pathological conditions. After exemplifying the current knowledge on bone vasculature, this review will move on to exosomes, a novel hotspot of scientific research. Exosomes will be introduced starting from their discovery via current isolation procedures and state-of-the-art characterization to their role in bone vascular development, homeostasis, and bone regeneration and repair while summarizing the underlying signal transduction pathways. With respect to their role in these processes, especially mesenchymal stem cell-derived extracellular vesicles are of interest, which leads to a discussion on patented applications and an update on ongoing clinical trials. Taken together, this review provides an overview of bone vasculature and bone regeneration, with a major focus on how exosomes influence this intricate system, as they might be useful for therapeutic purposes in the near future.

show abstract

Aberrant and Ectopic Cell Populations of the Fibrotic Pushing Border in Restrictive Allograft Syndrome after Lung Transplantation

Leiber,

Christian,

Neubert

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

RationaleRestrictive allograft syndrome (RAS) is a major cause of mortality in patients following lung transplantation due to rapid progressive fibrosis in the pulmonary graft. We have only limited knowledge of the cellular and molecular mechanisms that characterize the fibrosis in the RAS lung.ObjectiveTo elucidate cellularly-resolved transcriptomic and histologic characteristics of the structural cells in human RAS lungs.MethodsSingle-nuclei RNA-sequencing was performed in peripheral lung tissues from 15 RAS patients undergoing lung re-transplantation, and from 9 healthy control lungs. Findings were validated and complemented by various histologic techniques, including immunofluorescence, RNAscope, combined Elastica van Gieson-immunohistochemistry stains, and micro-CT scans.Measurement and Main resultsDifferential gene expression analysis of our single-nuclei RNA-sequencing data revealed in human RAS lungs previously undescribed and uniquely distributed aberrant basaloid cells, ectopicCOL15A1+vascular endothelial cells, andCTHRC1+fibrotic fibroblasts, all first characterized in idiopathic pulmonary fibrosis (IPF). In contrast to IPF, RAS lacks the cellular equivalent of bronchiolization. Histologic stains confirmed our transcriptomic discoveries and disclosed distinctive distribution patterns: Aberrant basaloid cells are primarily localized at the edge of the fibrotic pushing border, forming together with the juxtaposedCTHRC1+fibrotic fibroblasts the fibrotic niche of alveolar fibroelastosis (AFE), the histopathological hallmark in RAS lungs. On the endothelial side,PRX+alveolar microvasculature is lost in AFE areas. Micro-CT scans revealed that blood supply, now facilitated by expanded and ectopicCOL15A1+VE cells, changes from pulmonary to systemic perfusion. Last, our data reveals potential therapeutically-modifiable expression patterns in RAS, including genes coding for the integrin subunits αvβ6, activators of TGFβ.ConclusionConsidering the marked clinical, histologic and etiologic dissimilarities of RAS and IPF, our snRNAseq study revealed a surprising general principle of cellular and molecular pathogenesis in the fibrosing lung: the entity-spanning composition of the fibrotic niche by a) aberrant basaloid cells localized at the fibrotic pushing border, b) ectopicCOL15A1+vascular ECs and c) effectorCTHRC1+fibrotic fibroblasts. This general principle justifies a flexible but cellular pathogenesis-guided transferability of potential therapeutic approaches between progressive fibrotic lung diseases.

show abstract

The role of vasculature and angiogenesis in respiratory diseases

Cited by 7 publications

References 180 publications

Anti-angiogenic therapy in head and neck squamous cell carcinoma - current limitations and future directions

Anti-angiogenic therapy in head and neck squamous cell carcinoma - current limitations and future directions

Exosomes: A New Hope for Angiogenesis-Mediated Bone Regeneration

Aberrant and Ectopic Cell Populations of the Fibrotic Pushing Border in Restrictive Allograft Syndrome after Lung Transplantation

Contact Info

Product

Resources

About