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MIF and CXCL12 in Cardiovascular Diseases: Functional Differences and Similarities.

van der Vorst EP, Döring Y, Weber C - Front Immunol (2015)

Bottom Line: In contrast to CXCL12, MIF is secreted in response to diverse inflammatory stimuli, and has been associated with a clear pro-inflammatory and pro-atherogenic role in multiple studies of patients and animal models.Ongoing research on CXCL12 points at a protective function of this chemokine in atherosclerotic lesion development.This review will focus on the role of CXCL12 and MIF and their differences and similarities in CAD of high risk patients.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich , Munich , Germany.

ABSTRACT
Coronary artery disease (CAD) as part of the cardiovascular diseases is a pathology caused by atherosclerosis, a chronic inflammatory disease of the vessel wall characterized by a massive invasion of lipids and inflammatory cells into the inner vessel layer (intima) leading to the formation of atherosclerotic lesions; their constant growth may cause complications such as flow-limiting stenosis and plaque rupture, the latter triggering vessel occlusion through thrombus formation. Pathophysiology of CAD is complex and over the last years many players have entered the picture. One of the latter being chemokines (small 8-12 kDa cytokines) and their receptors, known to orchestrate cell chemotaxis and arrest. Here, we will focus on the chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF-1) and the chemokine-like function chemokine, macrophage migration-inhibitory factor (MIF). Both are ubiquitously expressed and highly conserved proteins and play an important role in cell homeostasis, recruitment, and arrest through binding to their corresponding chemokine receptors CXCR4 (CXCL12 and MIF), ACKR3 (CXCL12), and CXCR2 (MIF). In addition, MIF also binds to the receptor CD44 and the co-receptor CD74. CXCL12 has mostly been studied for its crucial role in the homing of (hematopoietic) progenitor cells in the bone marrow and their mobilization into the periphery. In contrast to CXCL12, MIF is secreted in response to diverse inflammatory stimuli, and has been associated with a clear pro-inflammatory and pro-atherogenic role in multiple studies of patients and animal models. Ongoing research on CXCL12 points at a protective function of this chemokine in atherosclerotic lesion development. This review will focus on the role of CXCL12 and MIF and their differences and similarities in CAD of high risk patients.

No MeSH data available.


Related in: MedlinePlus

Similarities and differences of CXCL12 versus MIF function in cardiovascular disease. Both CXCL12 and MIF can bind to CXCR4. Additionally, CXCL12 can bind to ACKR3 (CXCR7), while MIF binds to CXCR2 and CD74/CD44. Although MIF interaction with ACKR3 has been described for platelets, it is still unclear whether this is via direct binding or via receptor heterodimerization. Both chemokines have an important role in leukocyte recruitment, although cell-type-specific effects remain unknown. Besides this, CXCL12 and MIF have individual functions associated with cardiovascular disease.
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Figure 1: Similarities and differences of CXCL12 versus MIF function in cardiovascular disease. Both CXCL12 and MIF can bind to CXCR4. Additionally, CXCL12 can bind to ACKR3 (CXCR7), while MIF binds to CXCR2 and CD74/CD44. Although MIF interaction with ACKR3 has been described for platelets, it is still unclear whether this is via direct binding or via receptor heterodimerization. Both chemokines have an important role in leukocyte recruitment, although cell-type-specific effects remain unknown. Besides this, CXCL12 and MIF have individual functions associated with cardiovascular disease.

Mentions: This review will give a short overview of the current knowledge about atherosclerosis, mainly focusing on the inflammatory aspects and the role of chemokines. Subsequently, the role of two important inflammatory mediators that recently have been connected with CVD and atherosclerosis will be discussed and put into clinical perspective, namely the chemokines CXCL12 and macrophage migration-inhibitory factor (MIF, Table 1 and Figure 1).


MIF and CXCL12 in Cardiovascular Diseases: Functional Differences and Similarities.

van der Vorst EP, Döring Y, Weber C - Front Immunol (2015)

Similarities and differences of CXCL12 versus MIF function in cardiovascular disease. Both CXCL12 and MIF can bind to CXCR4. Additionally, CXCL12 can bind to ACKR3 (CXCR7), while MIF binds to CXCR2 and CD74/CD44. Although MIF interaction with ACKR3 has been described for platelets, it is still unclear whether this is via direct binding or via receptor heterodimerization. Both chemokines have an important role in leukocyte recruitment, although cell-type-specific effects remain unknown. Besides this, CXCL12 and MIF have individual functions associated with cardiovascular disease.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508925&req=5

Figure 1: Similarities and differences of CXCL12 versus MIF function in cardiovascular disease. Both CXCL12 and MIF can bind to CXCR4. Additionally, CXCL12 can bind to ACKR3 (CXCR7), while MIF binds to CXCR2 and CD74/CD44. Although MIF interaction with ACKR3 has been described for platelets, it is still unclear whether this is via direct binding or via receptor heterodimerization. Both chemokines have an important role in leukocyte recruitment, although cell-type-specific effects remain unknown. Besides this, CXCL12 and MIF have individual functions associated with cardiovascular disease.
Mentions: This review will give a short overview of the current knowledge about atherosclerosis, mainly focusing on the inflammatory aspects and the role of chemokines. Subsequently, the role of two important inflammatory mediators that recently have been connected with CVD and atherosclerosis will be discussed and put into clinical perspective, namely the chemokines CXCL12 and macrophage migration-inhibitory factor (MIF, Table 1 and Figure 1).

Bottom Line: In contrast to CXCL12, MIF is secreted in response to diverse inflammatory stimuli, and has been associated with a clear pro-inflammatory and pro-atherogenic role in multiple studies of patients and animal models.Ongoing research on CXCL12 points at a protective function of this chemokine in atherosclerotic lesion development.This review will focus on the role of CXCL12 and MIF and their differences and similarities in CAD of high risk patients.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich , Munich , Germany.

ABSTRACT
Coronary artery disease (CAD) as part of the cardiovascular diseases is a pathology caused by atherosclerosis, a chronic inflammatory disease of the vessel wall characterized by a massive invasion of lipids and inflammatory cells into the inner vessel layer (intima) leading to the formation of atherosclerotic lesions; their constant growth may cause complications such as flow-limiting stenosis and plaque rupture, the latter triggering vessel occlusion through thrombus formation. Pathophysiology of CAD is complex and over the last years many players have entered the picture. One of the latter being chemokines (small 8-12 kDa cytokines) and their receptors, known to orchestrate cell chemotaxis and arrest. Here, we will focus on the chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF-1) and the chemokine-like function chemokine, macrophage migration-inhibitory factor (MIF). Both are ubiquitously expressed and highly conserved proteins and play an important role in cell homeostasis, recruitment, and arrest through binding to their corresponding chemokine receptors CXCR4 (CXCL12 and MIF), ACKR3 (CXCL12), and CXCR2 (MIF). In addition, MIF also binds to the receptor CD44 and the co-receptor CD74. CXCL12 has mostly been studied for its crucial role in the homing of (hematopoietic) progenitor cells in the bone marrow and their mobilization into the periphery. In contrast to CXCL12, MIF is secreted in response to diverse inflammatory stimuli, and has been associated with a clear pro-inflammatory and pro-atherogenic role in multiple studies of patients and animal models. Ongoing research on CXCL12 points at a protective function of this chemokine in atherosclerotic lesion development. This review will focus on the role of CXCL12 and MIF and their differences and similarities in CAD of high risk patients.

No MeSH data available.


Related in: MedlinePlus