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Role of lectin-like oxidized low density lipoprotein-1 in fetoplacental vascular dysfunction in preeclampsia.

Zuniga FA, Ormazabal V, Gutierrez N, Aguilera V, Radojkovic C, Veas C, Escudero C, Lamperti L, Aguayo C - Biomed Res Int (2014)

Bottom Line: Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells.However, the role of this receptor in placental tissue is still unknown.In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, 4070386 Concepcion, Chile.

ABSTRACT
The bioavailability of nitric oxide (NO) represents a key marker in vascular health. A decrease in NO induces a pathological condition denominated endothelial dysfunction, syndrome observed in different pathologies, such as obesity, diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE). PE is one of the major risks for maternal death and fetal loss. Recent studies suggest that the placenta of pregnant women with PE express high levels of lectin-like oxidized LDL receptor-1 (LOX-1), which induces endothelial dysfunction by increasing reactive oxygen species (ROS) and decreasing intracellular NO. Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells. However, the role of this receptor in placental tissue is still unknown. In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE.

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Related in: MedlinePlus

Structure and LOX-1 signaling. LOX-1 has four domains: cytosolic domain (1–34 amino acids), transmembrane domain (amino acids 35–61), neck domain (amino acids 62–143), and CTLD (amino acids 144–263). The LOX-1 activation by different ligand increases phosphorylation of p42/44MAPK and p38MAPK and the expression of gp91phox subunit of NADPH oxidase, causing an increase in reactive oxygen species and a decrease in NO and hence endothelial dysfunction manifested by cell apoptosis, thrombosis, inflammation, and vasoconstriction.
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fig1: Structure and LOX-1 signaling. LOX-1 has four domains: cytosolic domain (1–34 amino acids), transmembrane domain (amino acids 35–61), neck domain (amino acids 62–143), and CTLD (amino acids 144–263). The LOX-1 activation by different ligand increases phosphorylation of p42/44MAPK and p38MAPK and the expression of gp91phox subunit of NADPH oxidase, causing an increase in reactive oxygen species and a decrease in NO and hence endothelial dysfunction manifested by cell apoptosis, thrombosis, inflammation, and vasoconstriction.

Mentions: Through ROS generation, LOX-1 stimulates gene expression by activating two signal transduction pathways involving either p38MAPK or ERK1/2 and PI3K, both causing NF-κB activation [22, 23]. NF-κB regulates expression of vascular genes including P-selectin, VCAM-1, ICAM-1, MCP-1, and M-CFS, involved in the attachment and activation of monocytes [66–68]. Decrease of eNOS and Bcl-2 and increase of matrix metalloproteases (MMP1, 3, 9) and Fas expression cause cells injury and apoptosis of endothelial cells [69]. LOX-1 activation can also lead to cell proliferation that is blocked with anti-LOX-1 neutralizing antibody. Recent evidence has shown that a complex formed by LOX-1 and membrane type 1 matrix metalloproteinase (MT1-MMP) plays a crucial role in RhoA and Rac1 activation signaling pathways in Ox-LDL stimulation. Blockade of LOX-1 or MT1-MMP inhibits cell invasion, endothelial NO synthase protein downregulation, RhoA-dependent and NADPH oxidase activity, and reactive oxygen species generation, mediated by Rac-1 [70]. All these evidences suggest the close relationship between NO bioavailability and ROS generation during LOX-1 activation in human endothelial cells (Figure 1).


Role of lectin-like oxidized low density lipoprotein-1 in fetoplacental vascular dysfunction in preeclampsia.

Zuniga FA, Ormazabal V, Gutierrez N, Aguilera V, Radojkovic C, Veas C, Escudero C, Lamperti L, Aguayo C - Biomed Res Int (2014)

Structure and LOX-1 signaling. LOX-1 has four domains: cytosolic domain (1–34 amino acids), transmembrane domain (amino acids 35–61), neck domain (amino acids 62–143), and CTLD (amino acids 144–263). The LOX-1 activation by different ligand increases phosphorylation of p42/44MAPK and p38MAPK and the expression of gp91phox subunit of NADPH oxidase, causing an increase in reactive oxygen species and a decrease in NO and hence endothelial dysfunction manifested by cell apoptosis, thrombosis, inflammation, and vasoconstriction.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109675&req=5

fig1: Structure and LOX-1 signaling. LOX-1 has four domains: cytosolic domain (1–34 amino acids), transmembrane domain (amino acids 35–61), neck domain (amino acids 62–143), and CTLD (amino acids 144–263). The LOX-1 activation by different ligand increases phosphorylation of p42/44MAPK and p38MAPK and the expression of gp91phox subunit of NADPH oxidase, causing an increase in reactive oxygen species and a decrease in NO and hence endothelial dysfunction manifested by cell apoptosis, thrombosis, inflammation, and vasoconstriction.
Mentions: Through ROS generation, LOX-1 stimulates gene expression by activating two signal transduction pathways involving either p38MAPK or ERK1/2 and PI3K, both causing NF-κB activation [22, 23]. NF-κB regulates expression of vascular genes including P-selectin, VCAM-1, ICAM-1, MCP-1, and M-CFS, involved in the attachment and activation of monocytes [66–68]. Decrease of eNOS and Bcl-2 and increase of matrix metalloproteases (MMP1, 3, 9) and Fas expression cause cells injury and apoptosis of endothelial cells [69]. LOX-1 activation can also lead to cell proliferation that is blocked with anti-LOX-1 neutralizing antibody. Recent evidence has shown that a complex formed by LOX-1 and membrane type 1 matrix metalloproteinase (MT1-MMP) plays a crucial role in RhoA and Rac1 activation signaling pathways in Ox-LDL stimulation. Blockade of LOX-1 or MT1-MMP inhibits cell invasion, endothelial NO synthase protein downregulation, RhoA-dependent and NADPH oxidase activity, and reactive oxygen species generation, mediated by Rac-1 [70]. All these evidences suggest the close relationship between NO bioavailability and ROS generation during LOX-1 activation in human endothelial cells (Figure 1).

Bottom Line: Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells.However, the role of this receptor in placental tissue is still unknown.In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, 4070386 Concepcion, Chile.

ABSTRACT
The bioavailability of nitric oxide (NO) represents a key marker in vascular health. A decrease in NO induces a pathological condition denominated endothelial dysfunction, syndrome observed in different pathologies, such as obesity, diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE). PE is one of the major risks for maternal death and fetal loss. Recent studies suggest that the placenta of pregnant women with PE express high levels of lectin-like oxidized LDL receptor-1 (LOX-1), which induces endothelial dysfunction by increasing reactive oxygen species (ROS) and decreasing intracellular NO. Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells. However, the role of this receptor in placental tissue is still unknown. In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE.

Show MeSH
Related in: MedlinePlus