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CD154: the atherosclerotic risk factor in rheumatoid arthritis?

Hassan GS, Yacoub D, Alaaeddine N, Nadiri A, Merhi Y, Mourad W - Arthritis Res. Ther. (2013)

Bottom Line: Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features.Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications.Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features. Indeed, evidence pertaining to this matter indicates that inflammation and its multiple components are the driving force behind the pathogenesis of these disorders. Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications. Indeed, CD154 signaling elicits critical inflammatory responses that are common to the pathogenesis of both diseases. Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients.

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Related in: MedlinePlus

CD154 and its receptors. Binding of CD154 to its classical CD40 counter-receptor regulates numerous critical biological responses. These mainly include B-cell-dependent isotype switching, cell-mediated immunity (production of cytokines, chemokines, adhesion molecules, growth factors, matrix metalloproteinases and procoagulants) and apoptosis. We have also shown that this interaction regulates platelet activation and thrombosis. The interaction of CD154 with the αIIbβ3 platelet integrin is involved in thrombus stabilization and may provide a novel outside-in signaling pathway by which platelets can be activated. CD154 can also bind to the inactive conformation of α5β1, and this interaction was shown to induce activation of the human monocytic U937 cell line. Finally, αMβ2 can mediate CD154-dependent inflammatory responses; in particular, leukocyte adhesion and neointimal formation. The pathophysiological relevance of these novel CD154-mediated interactions in inflammation remains elusive and additional studies will be required to address this issue.
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Figure 1: CD154 and its receptors. Binding of CD154 to its classical CD40 counter-receptor regulates numerous critical biological responses. These mainly include B-cell-dependent isotype switching, cell-mediated immunity (production of cytokines, chemokines, adhesion molecules, growth factors, matrix metalloproteinases and procoagulants) and apoptosis. We have also shown that this interaction regulates platelet activation and thrombosis. The interaction of CD154 with the αIIbβ3 platelet integrin is involved in thrombus stabilization and may provide a novel outside-in signaling pathway by which platelets can be activated. CD154 can also bind to the inactive conformation of α5β1, and this interaction was shown to induce activation of the human monocytic U937 cell line. Finally, αMβ2 can mediate CD154-dependent inflammatory responses; in particular, leukocyte adhesion and neointimal formation. The pathophysiological relevance of these novel CD154-mediated interactions in inflammation remains elusive and additional studies will be required to address this issue.

Mentions: Although most vascular and immune complications associated with CD154 have been largely attributed to its interaction with CD40, recently identified additional receptors merit attention. These include the integrins αIIbβ3, α5β1 and αMβ2 (Figure 1).


CD154: the atherosclerotic risk factor in rheumatoid arthritis?

Hassan GS, Yacoub D, Alaaeddine N, Nadiri A, Merhi Y, Mourad W - Arthritis Res. Ther. (2013)

CD154 and its receptors. Binding of CD154 to its classical CD40 counter-receptor regulates numerous critical biological responses. These mainly include B-cell-dependent isotype switching, cell-mediated immunity (production of cytokines, chemokines, adhesion molecules, growth factors, matrix metalloproteinases and procoagulants) and apoptosis. We have also shown that this interaction regulates platelet activation and thrombosis. The interaction of CD154 with the αIIbβ3 platelet integrin is involved in thrombus stabilization and may provide a novel outside-in signaling pathway by which platelets can be activated. CD154 can also bind to the inactive conformation of α5β1, and this interaction was shown to induce activation of the human monocytic U937 cell line. Finally, αMβ2 can mediate CD154-dependent inflammatory responses; in particular, leukocyte adhesion and neointimal formation. The pathophysiological relevance of these novel CD154-mediated interactions in inflammation remains elusive and additional studies will be required to address this issue.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672750&req=5

Figure 1: CD154 and its receptors. Binding of CD154 to its classical CD40 counter-receptor regulates numerous critical biological responses. These mainly include B-cell-dependent isotype switching, cell-mediated immunity (production of cytokines, chemokines, adhesion molecules, growth factors, matrix metalloproteinases and procoagulants) and apoptosis. We have also shown that this interaction regulates platelet activation and thrombosis. The interaction of CD154 with the αIIbβ3 platelet integrin is involved in thrombus stabilization and may provide a novel outside-in signaling pathway by which platelets can be activated. CD154 can also bind to the inactive conformation of α5β1, and this interaction was shown to induce activation of the human monocytic U937 cell line. Finally, αMβ2 can mediate CD154-dependent inflammatory responses; in particular, leukocyte adhesion and neointimal formation. The pathophysiological relevance of these novel CD154-mediated interactions in inflammation remains elusive and additional studies will be required to address this issue.
Mentions: Although most vascular and immune complications associated with CD154 have been largely attributed to its interaction with CD40, recently identified additional receptors merit attention. These include the integrins αIIbβ3, α5β1 and αMβ2 (Figure 1).

Bottom Line: Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features.Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications.Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features. Indeed, evidence pertaining to this matter indicates that inflammation and its multiple components are the driving force behind the pathogenesis of these disorders. Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications. Indeed, CD154 signaling elicits critical inflammatory responses that are common to the pathogenesis of both diseases. Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients.

Show MeSH
Related in: MedlinePlus