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Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence in a TXNIP-dependent manner.

Riahi Y, Kaiser N, Cohen G, Abd-Elrahman I, Blum G, Shapira OM, Koler T, Simionescu M, Sima AV, Zarkovic N, Zarkovic K, Orioli M, Aldini G, Cerasi E, Leibowitz G, Sasson S - J. Cell. Mol. Med. (2015)

Bottom Line: Previous studies showed that peroxisome proliferator-activated receptor (PPAR)δ was activated by 4-hydroalkenals, such as 4-HNE.Pharmacological interventions supported the involvement of the 4-HNE-PPARδ axis in the induction of TXNIP and VEC senescence.The association of TXNIP with VEC senescence was further supported by immunofluorescent staining of human carotid plaques in which the expression of both TXNIP and p21 was augmented in endothelial cells.

View Article: PubMed Central - PubMed

Affiliation: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.

No MeSH data available.


Related in: MedlinePlus

Suggested model of foam cell-induced VEC senescence. Foam cell-derived lipid peroxidation products, among which 4-HNE, reach VEC and activate PPARδ and subsequently increase the expression of TXNIP which augments oxidative stress and VEC senescence.
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fig07: Suggested model of foam cell-induced VEC senescence. Foam cell-derived lipid peroxidation products, among which 4-HNE, reach VEC and activate PPARδ and subsequently increase the expression of TXNIP which augments oxidative stress and VEC senescence.

Mentions: Cellular senescence has been linked to endothelial cell dysfunction and atherosclerosis 14,63. In the present study we investigated the mechanism involved in foam cell-induced VEC senescence. Using a co-culture system, in which VEC were exposed on the apical side to soluble factors released by foam cells 23,25, we found that the latter produced soluble factors that promoted SIPS in VEC. Our findings provide an important insight into the signal transduction pathway that culminated in endothelial cell senescence: foam cells derived from macrophages following exposure to OxLDL secreted lipid peroxidation products, including the nucleophilic aldehyde 4-HNE. The latter interacted with VEC and activated the nuclear factor PPARδ, which transactivated the TXNIP promoter. Consequently, TXNIP expression was increased, promoting senescence in the endothelial cells (see model in Fig.7).


Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence in a TXNIP-dependent manner.

Riahi Y, Kaiser N, Cohen G, Abd-Elrahman I, Blum G, Shapira OM, Koler T, Simionescu M, Sima AV, Zarkovic N, Zarkovic K, Orioli M, Aldini G, Cerasi E, Leibowitz G, Sasson S - J. Cell. Mol. Med. (2015)

Suggested model of foam cell-induced VEC senescence. Foam cell-derived lipid peroxidation products, among which 4-HNE, reach VEC and activate PPARδ and subsequently increase the expression of TXNIP which augments oxidative stress and VEC senescence.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549039&req=5

fig07: Suggested model of foam cell-induced VEC senescence. Foam cell-derived lipid peroxidation products, among which 4-HNE, reach VEC and activate PPARδ and subsequently increase the expression of TXNIP which augments oxidative stress and VEC senescence.
Mentions: Cellular senescence has been linked to endothelial cell dysfunction and atherosclerosis 14,63. In the present study we investigated the mechanism involved in foam cell-induced VEC senescence. Using a co-culture system, in which VEC were exposed on the apical side to soluble factors released by foam cells 23,25, we found that the latter produced soluble factors that promoted SIPS in VEC. Our findings provide an important insight into the signal transduction pathway that culminated in endothelial cell senescence: foam cells derived from macrophages following exposure to OxLDL secreted lipid peroxidation products, including the nucleophilic aldehyde 4-HNE. The latter interacted with VEC and activated the nuclear factor PPARδ, which transactivated the TXNIP promoter. Consequently, TXNIP expression was increased, promoting senescence in the endothelial cells (see model in Fig.7).

Bottom Line: Previous studies showed that peroxisome proliferator-activated receptor (PPAR)δ was activated by 4-hydroalkenals, such as 4-HNE.Pharmacological interventions supported the involvement of the 4-HNE-PPARδ axis in the induction of TXNIP and VEC senescence.The association of TXNIP with VEC senescence was further supported by immunofluorescent staining of human carotid plaques in which the expression of both TXNIP and p21 was augmented in endothelial cells.

View Article: PubMed Central - PubMed

Affiliation: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.

No MeSH data available.


Related in: MedlinePlus