Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs

AbstractThe human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD.

Download Full-text

Computational analysis revealing that K634 and T681 mutations modulate the 3D-structure of PDGFR-β and lead to sunitinib resistance

RSC Advances ◽

10.1039/c7ra01305a ◽

2017 ◽

Vol 7 (60) ◽

pp. 37612-37626 ◽

Cited By ~ 11

Author(s):

Vishal Nemaysh ◽

Pratibha Mehta Luthra

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Blood Vessels ◽

Computational Analysis ◽

3D Structure ◽

Growth Factor Receptor ◽

Platelet Derived Growth Factor ◽

Receptor Beta

Platelet-derived growth factor receptor-beta (PDGFR-β) is expressed by endothelial cells (ECs) of tumor-associated blood vessels and regulates primarily early hematopoiesis.

Download Full-text

Role of Leukocytes and Endothelial Cells in the Development of Angiogenesis in Inflammation and Wound Healing

Archives of Pathology & Laboratory Medicine ◽

10.5858/2001-125-0067-rolaec ◽

2001 ◽

Vol 125 (1) ◽

pp. 67-71 ◽

Cited By ~ 2

Author(s):

Mark W. Lingen

Keyword(s):

Wound Healing ◽

Endothelial Cells ◽

Blood Vessels ◽

Peripheral Blood ◽

Inflammatory Process ◽

Signs And Symptoms ◽

Critical Component ◽

Complex Environment ◽

Seminal Article

Abstract The basic signs and symptoms of inflammation and wound healing have been appreciated for thousands of years. However, the specific cells involved and their roles in this complex environment are still being elucidated today. In 1926, the origin of the phagocytic mononuclear ameboid wandering cell (macrophage) had not been determined. One popular theory was that the cells were differentiated from the endothelial cells of the nearby blood vessels, whereas others believed that the cells came from the peripheral blood or resting wandering cells. The purpose of this article is to review the seminal article published by Lang regarding this topic nearly 75 years ago. In addition, this article will review what is now known with regard to the role of the macrophage and endothelial cells in the development of angiogenesis, which is arguably the most critical component of successful inflammatory process or wound healing.

Download Full-text

Multiple endothelial cells constitute the tip of developing blood vessels and polarize to promote lumen formation

Development ◽

10.1242/dev.110296 ◽

2014 ◽

Vol 141 (21) ◽

pp. 4121-4126 ◽

Cited By ~ 20

Author(s):

J. C. Pelton ◽

C. E. Wright ◽

M. Leitges ◽

V. L. Bautch

Keyword(s):

Endothelial Cells ◽

Blood Vessels ◽

Lumen Formation

Download Full-text

Phospholipase Cγ Activation Drives Increased Production of Autotaxin in Endothelial Cells and Lysophosphatidic Acid-Dependent Regression

Molecular and Cellular Biology ◽

10.1128/mcb.01275-09 ◽

2010 ◽

Vol 30 (10) ◽

pp. 2401-2410 ◽

Cited By ~ 31

Author(s):

Eunok Im ◽

Ruta Motiejunaite ◽

Jorge Aranda ◽

Eun Young Park ◽

Lorenzo Federico ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Vessels ◽

Lysophosphatidic Acid ◽

Vascular Endothelial ◽

Additional Mechanism ◽

Phospholipase Cγ1 ◽

Common Substrate ◽

Phosphoinositide 3 Kinase ◽

Endothelial Growth Factor

ABSTRACT We previously reported that vascular endothelial growth factor (VEGF)-dependent activation of phospholipase Cγ1 (PLCγ) regulated tube stability by competing with phosphoinositide 3-kinase (PI3K) for their common substrate. Here we describe an additional mechanism by which PLCγ promoted regression of tubes and blood vessels. Namely, it increased the level of autotaxin (ATX), which is a secreted form of lysophospholipase D that produces lysophosphatidic acid (LPA). LPA promoted motility of endothelial cells, leading to disorganization/regression of tubes in vitro. Furthermore, mice that under- or overexpressed members of this intrinsic destabilization pathway showed either delayed or accelerated, respectively, regression of blood vessels. We conclude that endothelial cells can be instructed to engage a PLCγ-dependent intrinsic destabilization pathway that results in the production of soluble regression factors such as ATX and LPA. These findings are likely to potentiate ongoing efforts to prevent, manage, and eradicate numerous angiogenesis-based diseases such as proliferative diabetic retinopathy and solid tumors.

Download Full-text

Interaction of the Pseudomonas aeruginosa secretory products pyocyanin and pyochelin generates hydroxyl radical and causes synergistic damage to endothelial cells. Implications for Pseudomonas-associated tissue injury.

Journal of Clinical Investigation ◽

10.1172/jci116104 ◽

1992 ◽

Vol 90 (6) ◽

pp. 2187-2196 ◽

Cited By ~ 92

Author(s):

B E Britigan ◽

T L Roeder ◽

G T Rasmussen ◽

D M Shasby ◽

M L McCormick ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Endothelial Cells ◽

Hydroxyl Radical ◽

Tissue Injury ◽

Secretory Products

Download Full-text

Human iPSC-derived mesodermal progenitor cells preserve their vasculogenesis potential after extrusion and form hierarchically organized blood vessels

10.1101/2021.05.09.443303 ◽

2021 ◽

Author(s):

Leyla Dogan ◽

Ruben Scheuring ◽

Nicole Wagner ◽

Yuichiro Ueda ◽

Philipp Woersdoerfer ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Vessels ◽

Progenitor Cells ◽

Vessel Wall ◽

De Novo ◽

Hierarchical Organization ◽

Wall Structure ◽

Electron Microscopic ◽

Vessel Formation

Post-fabrication formation of a proper vasculature remains an unresolved challenge in bioprinting. Established strategies focus on the supply of the fabricated structure with nutrients and oxygen and either rely on the mere formation of a channel system using fugitive inks, or additionally use mature endothelial cells and/or peri-endothelial cells such as smooth muscle cells for the formation of blood vessels in vitro. Functional vessels, however, exhibit a hierarchical organization and multilayered wall structure that is important for their function. Human induced pluripotent stem cell-derived mesodermal progenitor cells (hiMPCs) have been shown to possess the capacity to form blood vessels in vitro, but have so far not been assessed for their applicability in bioprinting processes. Here, we demonstrate that hiMPCs, after formulation into an alginate/collagen type 1 bioink and subsequent extrusion, retain their ability to give rise to the formation of complex vessels that display a hierarchical network in a process that mimicks the embryonic steps of vessel formation by vasculogenesis. Histological evaluations at different time points of extrusion revealed initial formation of spheres, followed by lumen formation and further structural maturation as evidenced by building a multilayered vessel wall and a vascular network. These findings are supported by immunostainings for endothelial and peri-endothelial cell markers as well as electron microscopic analyses at the ultrastructural level. Moreover, capillary-like vessel structures deposited a basement membrane-like matrix structure at the basal side between the vessel wall and the alginate-collagen matrix. These results evidence the applicability and great potential of hiMPCs for the bioprinting of vascular structures mimicking the basic morphogenetic steps of de novo vessel formation during embryogenesis.

Download Full-text

Kisspeptin-10 Inhibits Angiogenesis in Human Placental Vessels ex Vivo and Endothelial Cells in Vitro

Endocrinology ◽

10.1210/en.2010-0565 ◽

2010 ◽

Vol 151 (12) ◽

pp. 5927-5934 ◽

Cited By ~ 32

Author(s):

Thayalini Ramaesh ◽

James J. Logie ◽

Antonia K. Roseweir ◽

Robert P. Millar ◽

Brian R. Walker ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Vessels ◽

Ex Vivo ◽

Umbilical Vein ◽

Biologically Active ◽

Trophoblast Invasion ◽

In Vitro Assays ◽

Dependent Manner ◽

Inhibition Of Proliferation

Recent studies suggest that kisspeptin (a neuropeptide central to the regulation of gonadotrophin secretion) has diverse roles in human physiology, including a putative role in implantation and placental function. Kisspeptin and its receptor are present in human blood vessels, where they mediate vasoconstriction, and kisspeptin is known to inhibit tumor metastasis and trophoblast invasion, both processes involving angiogenesis. We hypothesized that kisspeptin contributes to the regulation of angiogenesis in the reproductive system. The presence of the kisspeptin receptor was confirmed in human placental blood vessels and human umbilical vein endothelial cells (HUVEC) using immunochemistry. The ability of kisspeptin-10 (KP-10) (a shorter biologically active processed peptide) to inhibit angiogenesis was tested in explanted human placental arteries and HUVEC using complementary ex vivo and in vitro assays. KP-10 inhibited new vessel sprouting from placental arteries embedded in Matrigel and tube-like structure formation by HUVEC, in a concentration-dependent manner. KP-10 had no effect on HUVEC viability or apoptosis but induced concentration-dependent inhibition of proliferation and migration. In conclusion, KP-10 has antiangiogenic effects and, given its high expression in the placenta, may contribute to the regulation of angiogenesis in this tissue.

Download Full-text

Casting Cells

Microscopy Today ◽

10.1017/s1551929500056868 ◽

2001 ◽

Vol 9 (3) ◽

pp. 3-5

Author(s):

Stephen W. Carmichael

Keyword(s):

Endothelial Cells ◽

Electron Microscope ◽

Scanning Electron Microscope ◽

Silver Nitrate ◽

Blood Vessels ◽

Nerve Fiber ◽

Corrosion Casts ◽

New Information ◽

Scanning Electron

It's always refreshing to read about two old techniques being combined in a novel way to yield new information. Osamu Ohtani and Yuko Ohtani recently accomplished this. Louis Ranvier probably introduced the use of silver nitrate as a histology stain over a century ago. Whereas Ranvier is best known for describing nodes along the nerve fiber, he also demonstrated that silver nitrate stained endothelial cells, allowing their borders to be clearly visualized. In the 1970's, Takuro Murakami first used the scanning electron microscope (SEM) to examine corrosion casts of the vasculature. Much of what we currently know about the microarchitecture of blood vessels has been discovered using this technique.

Download Full-text