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Atherosclerosis

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Novel aspects of the pathogenesis of aneurysms of the abdominal aorta in humans

Michel JB et al. Cardiovasc Res (2011) 90(1): 18-27 doi:10.1093/cvr/cvq337 - Click here to view the abstract 



 

There are now clinical, biological, and radiological data establishing that intraluminal thrombus (ILT) in abdominal aortic aneurysm (AAA) is one of the driving forces of the evolution of dilation toward rupture. ILT is a main source of
1) oxidation, due to the red blood cell (RBC) storage and haem-iron release, and
2) proteolytic activities in AAA, including activation of plasmin and retention of neutrophils, and it is a potential site of weak pathogen contamination.
The pathogenic spatio-temporal role of ILT is directly linked to its permanent renewal at the luminal interface with circulating blood and to the high porosity of this neo-tissue, allowing pressure-dependent outward radial convection of proteases and oxidized molecular mediators towards the arterial wall and the adventitia. Therefore, ILT biology impacts vascular smooth muscle cell disappearance and extracellular matrix degradation in the medial layer of the arterial wall and the angiogenic and adaptive immune responses taking place in the adventitia of AAA.


Proteins mediating collagen biosynthesis and accumulation in arterial repair: novel targets for anti-restenosis therapy

Osherov AB et al. Cardiovasc Res (2011) 91(1): 16-26 doi:10.1093/cvr/cvr012 - Click here to view the abstract 



 

Effects of matrix metalloproteinases (MMPs) in the vessel wall


Proteins mediating collagen biosynthesis and accumulation in arterial repair: novel targets for anti-restenosis therapy

Osherov AB et al. Cardiovasc Res (2011) 91(1): 16-26 doi:10.1093/cvr/cvr012 - Click here to view the abstract 
 


 

Receptor signaling pathways affecting extracellular matrix synthesis in the arterial wall in response to vascular injury. See text for details. Red arrow indicates inhibition, green arrow indicates activation, yellow arrow indicates signal transduction to the nucleus. VSMC, vascular smooth muscle cell. TGF-β, transforming growth factor beta, PDGF, platelet-derived growth factor. MMPs, matrix metalloproteinases, ET, endothelin.


Endothelial cell-borne platelet bridges selectively recruit monocytes in human and mouse models of vascular inflammation

Kuckleburg CJ et al. Cardiovasc Res (2011) 91(1): 134-141 doi:10.1093/cvr/cvr040 - Click here to view the abstract 



 

The mechanisms by which secretory SMCs promote the recruitment of monocytes from flowing blood.

The routes by which inflammatory leucocytes are recruited to the artery wall and are enriched within the atherosclerotic environment are poorly described. Here, observations using co-culture and animal models of the diseased artery wall, allied with data from previous studies, show that interactions between cells of the diseased artery wall can generate signals that coordinate the preferential recruitment of monocytes from flowing blood. This process depends upon crosstalk between secretory smooth muscle cells (SMCs) and endothelial cells (ECs), which leads to the plasmin-dependent generation of active transforming growth factor-β1 (TGF-β1). This agent induces von Willebrand factor (vWF) expression on ECs so that platelets are recruited and activated and act as an adhesive bridge between the EC surface and the flowing blood. Monocytes are preferentially recruited from blood by tethering to platelet P-selectin and preferentially activated by CCL2 (MCP-1), which is released from ECs by the action of the platelet chemokine CXCL4 (PF4; platelet factor 4), stimulating the endothelial cell receptor CXCR3b.

This process greatly enriches for monocytes at the EC surface and supports monocyte transmigration. Thus, a series of cellular and molecular interactions initiated by cells resident within the diseased artery are shown to result in the specific recruitment of the predominant population of inflammatory leucocytes recruited during atherogenesis.

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