Abstract 353: Elastase-Activated Stress Response of Vascular Cells

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Irina Grechowa ◽  
Bernhard Dorweiler ◽  
Anja Wallrath ◽  
Sven Horke
Keyword(s):  
Flow Cytometry ◽  
Endothelial Cells ◽  
Cell Death ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Apoptotic Cell ◽  
Muscle Cells ◽  
Apoptotic Cell Death ◽  
Atherosclerotic Plaques ◽  
Vascular Cells

Introduction: Rupture of atherosclerotic plaques is the most abundant cause for stroke. The serine protease elastase plays an important role as it induces death of endothelial cells (ECs) and smooth muscle cells (SMCs), and breaks down the fibrous cap of atherosclerotic plaques. Increased elastase concentrations were found in patients with symptomatic stenosis. We previously showed that elastase activates the endoplasmic reticulum (ER) stress signaling pathway unfolded protein response (UPR) in rupture-prone plaques of human carotid artery. However, signaling pathways elicited by elastase in vascular cells were largely unknown. We hypothesized that elastase induces cell-type dependent responses in ECs, SMCs and macrophages (M[[Unable to Display Character: &#1060;]]). Methods and Results: Different forms of cell death and UPR activation were analyzed in primary and immortalized endothelial cells, coronary artery smooth muscle cells (HCASMCs) and M[[Unable to Display Character: &#1060;]] after treatment with human neutrophil elastase. To discriminate between the involved cell death types, three independent assays were performed. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-assay by confocal microscopy (p < .01), caspase3/7 activity by chemiluminescence-assays (p < .01) and cell-cycle analysis by flow cytometry revealed that an autophagic/apoptotic cell death was induced upon elastase treatment. This appeared specific for ECs, as it was absent in M[[Unable to Display Character: &#1060;]]. Necrosis (as determined by chemiluminescent lactate dehydrogenase-release assay) and necroptosis (assessed by flow cytometry) played only minor roles. The involvement of the UPR was investigated on protein and / or gene expression level. The high levels of GRP78, phospho-PERK, phospho-eIF2α, spliced XBP1 and CHOP indicate a strongly activated UPR that may give rise to the subsequent induced autophagic/apoptotic cell death. Conclusion: Elastase plays a significant role in plaque stability and cell survival likely through activation of a UPR/autophagic type of endothelial cell death. This may explain underlying molecular links how elastase destabilizes atherosclerotic plaques.

scholarly journals Cigarette Smoke Extract Causes Non-Apoptotic Cell Death in Neonatal Vascular Smooth Muscle Cells

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 294A-294A
Author(s):  
Namasivayam Ambalavanan ◽  
Waldemar F Carlo ◽  
Arlene Bulger ◽  
Jian Shi ◽  
Joseph B Philips
Keyword(s):  
Cell Death ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cigarette Smoke ◽  
Vascular Smooth Muscle Cells ◽  
Apoptotic Cell ◽  
Muscle Cells ◽  
Cigarette Smoke Extract ◽  
Apoptotic Cell Death

Abstract 505: Targeting FOXM1 in Vascular Smooth Muscle Cells Induces Apoptotic Cell Death

2018 ◽  
Vol 38 (Suppl_1) ◽  
Author(s):  
Sarah R Franco ◽  
Amelia Stranz ◽  
Fiona Ljumani ◽  
Go Urabe ◽  
Danielle Stewart ◽  
...  
Keyword(s):  
Cell Death ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Apoptotic Cell ◽  
Muscle Cells ◽  
Apoptotic Cell Death

scholarly journals Activation of αVβ3 on Vascular Cells Controls Recognition of Prothrombin

1998 ◽  
Vol 143 (7) ◽  
pp. 2081-2092 ◽  
Author(s):  
Tatiana V. Byzova ◽  
Edward F. Plow
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Blood Coagulation ◽  
Direct Interaction ◽  
Muscle Cells ◽  
Coagulation System ◽  
General Level ◽  
Vascular Cells ◽  
Blood Coagulation System

Regulation of vascular homeostasis depends upon collaboration between cells of the vessel wall and blood coagulation system. A direct interaction between integrin αVβ3 on endothelial cells and smooth muscle cells and prothrombin, the pivotal proenzyme of the blood coagulation system, is demonstrated and activation of the integrin is required for receptor engagement. Evidence that prothrombin is a ligand for αVβ3 on these cells include: (a) prothrombin binds to purified αVβ3 via a RGD recognition specificity; (b) prothrombin supports αVβ3-mediated adhesion of stimulated endothelial cells and smooth muscle cells; and (c) endothelial cells, either in suspension and in a monolayer, recognize soluble prothrombin via αVβ3. αVβ3-mediated cell adhesion to prothrombin, but not to fibrinogen, required activation of the receptor. Thus, the functionality of the αVβ3 receptor is ligand defined, and prothrombin and fibrinogen represent activation- dependent and activation-independent ligands. Activation of αVβ3 could be induced not only by model agonists, PMA and Mn2+, but also by a physiologically relevant agonist, ADP. Inhibition of protein kinase C and calpain prevented activation of αVβ3 on vascular cells, suggesting that these molecules are involved in the inside-out signaling events that activate the integrin. The capacity of αVβ3 to interact with prothrombin may play a significant role in the maintenance of hemostasis; and, at a general level, ligand selection by αVβ3 may be controlled by the activation state of this integrin.

Atorvastatin Sensitises Vascular Smooth Muscle Cells, but not Endothelial Cells, to TNF-α-induced Cell Death

2012 ◽  
Vol 18 (38) ◽  
pp. 6331-6338 ◽  
Author(s):  
Arturo Giordano ◽  
Simona Romano ◽  
Giovanna Nappo ◽  
Stefano Messina ◽  
Michele Polimeno ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Tnf Alpha

Migration of cultured vascular cells in response to plasma and platelet-derived factors

1982 ◽  
Vol 56 (1) ◽  
pp. 71-82
Author(s):  
L.R. Bernstein ◽  
H. Antoniades ◽  
B.R. Zetter
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Human Platelet ◽  
Muscle Cells ◽  
Cell Types ◽  
Vascular Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle

Phagokinetic migration of cultured vascular cells was tested in response to human platelet-rich serum (‘serum’) and human platelet-poor plasma serum (‘plasma’). The cell types tested included bovine aortic endothelial cells, human umbilical vein endothelial cells, human haemangiomal capillary endothelial cells, bovine adrenal microvascular pericytes, and bovine aortic smooth muscle cells. Human serum stimulated a significant increase in the rate of migration for all five cell types. Human plasma stimulated the endothelial cells to migrate but had no effect on the migration of pericytes or smooth muscle cells. Highly purified platelet-derived growth factor (PDGF) stimulated dose-dependent migration of smooth muscle cells causing a 50% increase in phagokinetic track area relative to controls. Neither pericyte nor endothelial cell migration was stimulated by PDGF. Rabbit antiserum to human PDGF completely blocked the smooth muscle cell migration induced by either 10% serum or 1 ng/ml pure PDGF. Purified platelet factor IV (PF4) stimulated migration of pericytes but not of smooth muscle cells nor endothelial cells. Sheep antiserum to human PF4 completely blocked the pericyte migration induced by either 10% serum or 1 microgram/ml pure PF4. These results indicate that PDGF is the primary factor in serum responsible for the migration of cultured aortic smooth muscle cells and that PF4 is a critical factor required to induce the migration of pericytes. Other factors present in both plasma and serum control the migration of vascular endothelial cells.

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