2019
DOI: 10.3390/toxins11110660
|View full text |Cite
|
Sign up to set email alerts
|

Hemolysis Derived Products Toxicity and Endothelium: Model of the Second Hit

Abstract: Vascular diseases are multifactorial, often requiring multiple challenges, or ‘hits’, for their initiation. Intra-vascular hemolysis illustrates well the multiple-hit theory where a first event lyses red blood cells, releasing hemolysis-derived products, in particular cell-free heme which is highly toxic for the endothelium. Physiologically, hemolysis derived-products are rapidly neutralized by numerous defense systems, including haptoglobin and hemopexin which scavenge hemoglobin and heme, respectively. Likew… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1
1

Citation Types

1
61
0
1

Year Published

2020
2020
2022
2022

Publication Types

Select...
9

Relationship

2
7

Authors

Journals

citations
Cited by 64 publications
(63 citation statements)
references
References 198 publications
(252 reference statements)
1
61
0
1
Order By: Relevance
“…This over activation is indeed at least in part heme‐dependent since it was inhibited by the heme scavenger hemopexin. In similar experimental settings, complement over activation on ECs was detected in the sera of patients with atypical hemolytic uremic syndrome, as well as from other diseases with intravascular hemolysis, such as HELLP syndrome (hemolysis, elevated liver enzymes, and a low platelet count) and preeclampsia . It is tempting to speculate that in these diseases, heme could be the trigger of EC activation, rendering them susceptible to complement activation .…”
Section: Discussionmentioning
confidence: 85%
“…This over activation is indeed at least in part heme‐dependent since it was inhibited by the heme scavenger hemopexin. In similar experimental settings, complement over activation on ECs was detected in the sera of patients with atypical hemolytic uremic syndrome, as well as from other diseases with intravascular hemolysis, such as HELLP syndrome (hemolysis, elevated liver enzymes, and a low platelet count) and preeclampsia . It is tempting to speculate that in these diseases, heme could be the trigger of EC activation, rendering them susceptible to complement activation .…”
Section: Discussionmentioning
confidence: 85%
“…In parallel, free Hb is highly toxic for endothelial cells [22]. Important frictional forces, involving RBCs colliding with endothelial cells are also, with time, the main determinant of endothelial abrasion in conductance arteries [23].…”
Section: Frictional Forces Involve Rbcs and Interact With Nitric Oxidmentioning
confidence: 99%
“…Finally, free heme may contribute to the inflammatory activation of the endothelium via complement activation as demonstrated in various experimental models of intravascular hemolysis ( 51 , 73 ). These studies have also provided experimental evidence that free heme may be an important second signal for pre-existing conditions of pro-inflammatory endothelial activation to further escalate the inflammatory vascular damage in disorders such as SCD and atypical hemolytic uremic syndrome ( 74 ).…”
Section: Heme As a Second Hit For Tlr4 Activationmentioning
confidence: 99%