scholarly journals New Molecular Mechanisms for Cardiovascular Disease: Blood Flow Sensing Mechanism in Vascular Endothelial Cells

2011 ◽  
Vol 116 (4) ◽  
pp. 323-331 ◽  
Author(s):  
Kimiko Yamamoto ◽  
Joji Ando
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Sensing Mechanism ◽  
Flow Sensing

Novel control of cAMP-regulated transcription in vascular endothelial cells

2012 ◽  
Vol 40 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Gillian R. Milne ◽  
Timothy M. Palmer ◽  
Stephen J. Yarwood
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Inflammatory Diseases ◽  
Circulatory System ◽  
Vascular Endothelial ◽  
Protective Mechanisms ◽  
Enhancer Binding Protein ◽  
Developed World

Chronic inflammatory diseases, such as atherosclerosis, are a major cause of death and disability in the developed world. In this respect, although cholesterol obviously plays a predominant role in atherosclerosis, targeting inflammation at lesion sites may be just as important. Indeed, elevated IL-6 (interleukin 6) levels are as strongly associated with coronary heart disease as increased cholesterol. We have been investigating novel cAMP-regulated pathways that combat the action of pro-inflammatory cytokines, such as IL-6 and leptin, in the VECs (vascular endothelial cells) of the circulatory system. In this respect, we have begun to unravel new molecular mechanisms by which the cAMP/Epac1 (exchange protein directly activated by cAMP 1)/Rap1 pathway can initiate a rigorous programme of protective anti-inflammatory responses in VECs. Central to this is the coupling of cAMP elevation to the mobilization of two C/EBP (CCAAT/enhancer-binding protein) family transcription factors, resulting in the induction of the SOCS3 (suppressor of cytokine signalling 3) gene, which attenuates pro-inflammatory cytokine signalling in VECs. These novel ‘protective’ mechanisms of cAMP action will inform the development of the next generation of pharmaceuticals specifically designed to combat endothelial inflammation associated with cardiovascular disease.

scholarly journals Disturbed flow: p53 SUMOylation in the turnover of endothelial cells

2011 ◽  
Vol 193 (5) ◽  
pp. 805-807 ◽  
Author(s):  
Wakako Takabe ◽  
Noah Alberts-Grill ◽  
Hanjoong Jo
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Protein Inhibitor ◽  
Disturbed Flow ◽  
Antiapoptotic Protein ◽  
Kinase C

Disturbed blood flow induces apoptosis of vascular endothelial cells, which causes atherosclerosis. In this issue, Heo et al. (2011. J. Cell Biol. doi:10.1083/jcb.201010051) sheds light on p53’s role in this phenomenon. Disturbed flow induces peroxynitrite production, which activates protein kinase C ζ and it’s binding to the E3 SUMO (small ubiquitin-like modifier) ligase PIASy (protein inhibitor of activated STATy). This leads to p53 SUMOylation and its export to the cytosol, where it binds to the antiapoptotic protein Bcl-2 to induce apoptosis.

Abstract 221: The P2x4 Receptor is Required for Neuroprotection via Ischemic Preconditioning

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Tomohiko Ozaki ◽  
Rieko Muramatsu ◽  
Toshiyuki Fujinaka ◽  
Toshiki Yoshimine ◽  
Toshihide Yamashita
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Endothelial Cells ◽  
Ischemic Tolerance ◽  
Receptor Expression ◽  
Vascular Endothelial ◽  
P2x4 Receptor ◽  
Flow Changes

Background: Ischemic preconditioning (IPC), a procedure consisting of transient ischemia and subsequent reperfusion, provides ischemic tolerance against prolonged ischemia in the brain. Although the blood flow changes mediated by IPC are primarily perceived by vascular endothelial cells, the role of these cells in ischemic tolerance has not fully clarified. In this research, we focused on the role of P2X4 receptor, which sense blood flow changes and is expressed on vascular endothelial cells. Methods: We administrated P2X4 receptor inhibitor into lateral ventricle of C57BL/6J male mice (8-10 weeks) and then conducted middle cerebral artery occlusion (MCAO). Fifteen minutes MCAO was done as IPC 48 hours before 60 minutes MCAO. To examine the necessity of P2X4 receptor expression in vascular endothelial cells, we generated a conditional knockout (CKO) mouse in which the P2X4 receptor was knocked down in VE-cadherin-positive vascular endothelial cells. To investigate molecular change by IPC, we obtained cerebrovascular endothelial cells of mice 48 hours after IPC, and real time PCR and ELISA were evaluated. To examine the molecular expression change on vascular endothelial cells by blood flow, we used in vitro culture system which generates fluid flow and real time PCR was evaluated. Inhibition of P2X4 receptor expression was conducted by P2X4 receptor siRNA transfection. Results: P2X4 receptor antagonist abolished neuroprotection via IPC. Moreover, the effect of IPC to P2X4 receptor CKO mice was smaller than control mice, the infarct volume of P2X4 receptor CKO was larger than control mice after 60 minutes MCAO (p<0.05, Control, n=4; CKO, n=6). IPC induced expression of osteopontin mRNA (p<0.05, n=5). Osteopontin administration attenuates the increase of infarct formation induced by P2X4 receptor inhibition (p<0.05, Control, n=5; Osteopontin, n=6). In vitro, shear stress upregulated expression of osteopontin mRNA (p<0.05, n=3). This upregulation was inhibited by P2X4 receptor siRNA (p<0.05, Control siRNA, n=6; P2X4 receptor siRNA, n=7). Conclusion: These results demonstrate a novel mechanism whereby vascular endothelial cells are involved in ischemic tolerance by way of the pathway about P2X4 receptor and osteopontin.

scholarly journals Generation of Functional Vascular Endothelial Cells and Pericytes from Keratinocyte Derived Human Induced Pluripotent Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 74
Author(s):  
Selin Pars ◽  
Kevin Achberger ◽  
Alexander Kleger ◽  
Stefan Liebau ◽  
Natalia Pashkovskaia
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Drug Testing ◽  
Embryoid Body ◽  
Vascular Endothelial Cells ◽  
Induced Pluripotent Stem Cell ◽  
Efficient Production ◽  
Vascular Endothelial ◽  
Marker Expression ◽  
Induced Pluripotent

Human induced pluripotent stem cell (hiPSC)-derived endothelial cells (ECs) and pericytes provide a powerful tool for cardiovascular disease modelling, personalized drug testing, translational medicine, and tissue engineering. Here, we report a novel differentiation protocol that results in the fast and efficient production of ECs and pericytes from keratinocyte-derived hiPSCs. We found that the implementation of a 3D embryoid body (EB) stage significantly improves the differentiation efficiency. Compared with the monolayer-based technique, our protocol yields a distinct EC population with higher levels of EC marker expression such as CD31 and vascular endothelial cadherin (VE-cadherin). Furthermore, the EB-based protocol allows the generation of functional EC and pericyte populations that can promote blood vessel-like structure formation upon co-culturing. Moreover, we demonstrate that the EB-based ECs and pericytes can be successfully used in a microfluidic chip model, forming a stable 3D microvascular network. Overall, the described protocol can be used to efficiently differentiate both ECs and pericytes with distinct and high marker expression from keratinocyte-derived hiPSCs, providing a potent source material for future cardiovascular disease studies.

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