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Large animal models of cardiovascular disease.

Tsang HG, Rashdan NA, Whitelaw CB, Corcoran BM, Summers KM, MacRae VE - Cell Biochem. Funct. (2016)

Bottom Line: In contrast, large animal models can show considerably greater similarity to humans.Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research.These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.

No MeSH data available.


Related in: MedlinePlus

Simplified diagram showing potential RANK/RANKL/OPG involvement in bone remodelling and in vascular calcification. Receptor activator of nuclear factor kappa‐B ligand (RANKL) from osteoblasts or endothelial cells binds to the Receptor Activator of Nuclear Factor kappa‐B (RANK) of osteoclast precursors, or vascular smooth muscle cells (VSMCs). This leads to differentiation into mature osteoclasts in the bone, which are involved in bone resorption, whereas in vascular calcification, VSMCs undergo a phenotypic transition into osteochondrogenic cells that can deposit mineralized matrix. Osteoprotegerin (OPG) is the decoy receptor for RANKL, and a potential inhibitor for mineralization
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cbf3173-fig-0002: Simplified diagram showing potential RANK/RANKL/OPG involvement in bone remodelling and in vascular calcification. Receptor activator of nuclear factor kappa‐B ligand (RANKL) from osteoblasts or endothelial cells binds to the Receptor Activator of Nuclear Factor kappa‐B (RANK) of osteoclast precursors, or vascular smooth muscle cells (VSMCs). This leads to differentiation into mature osteoclasts in the bone, which are involved in bone resorption, whereas in vascular calcification, VSMCs undergo a phenotypic transition into osteochondrogenic cells that can deposit mineralized matrix. Osteoprotegerin (OPG) is the decoy receptor for RANKL, and a potential inhibitor for mineralization

Mentions: Studies assessing the biological and structural changes in aortic valves have predominantly used mouse models. Techniques used have included staining for calcium deposition, quantitative real‐time PCR (qRT‐PCR) to examine changes in mRNA levels for specific genes, protein quantification and enzymatic activity 36. To date, there are reports of pro‐osteogenic signalling cascades thought to contribute to the initiation and progression of aortic stenosis. Signalling molecules include bone morphogenetic proteins (BMPs), Wnt/β‐catenin and transforming growth factor‐β (TGF‐β) although the role of TGF‐β in osteogenic signalling is not clear 36. The RANK/RANKL/OPG pathway is also thought to be involved in the calcification process, which involves complex interactions between receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) (Figure 2) 36, 37. Matrix remodelling may also be involved in the expansion of calcified plaques and pro‐inflammatory processes, through alterations in matrix metalloproteinases (MMPs) and elastin fragments produced by cathepsins 36. Furthermore, the NOTCH1 pathway has been implicated as a regulator of valve calcification, through the repression of the osteoblast transcription factor Runt‐related transcription factor 2 (RUNX2) (Figure 3) 38. This suggests an inhibitory role of NOTCH1 in valvular calcification. Additionally, a number of ECM proteins have been found to have roles in CAVD including collagen, elastin and GAGs, where changes in their expression have impacts on cellular processes, and also cause valve leaflet thickening 39.


Large animal models of cardiovascular disease.

Tsang HG, Rashdan NA, Whitelaw CB, Corcoran BM, Summers KM, MacRae VE - Cell Biochem. Funct. (2016)

Simplified diagram showing potential RANK/RANKL/OPG involvement in bone remodelling and in vascular calcification. Receptor activator of nuclear factor kappa‐B ligand (RANKL) from osteoblasts or endothelial cells binds to the Receptor Activator of Nuclear Factor kappa‐B (RANK) of osteoclast precursors, or vascular smooth muscle cells (VSMCs). This leads to differentiation into mature osteoclasts in the bone, which are involved in bone resorption, whereas in vascular calcification, VSMCs undergo a phenotypic transition into osteochondrogenic cells that can deposit mineralized matrix. Osteoprotegerin (OPG) is the decoy receptor for RANKL, and a potential inhibitor for mineralization
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4834612&req=5

cbf3173-fig-0002: Simplified diagram showing potential RANK/RANKL/OPG involvement in bone remodelling and in vascular calcification. Receptor activator of nuclear factor kappa‐B ligand (RANKL) from osteoblasts or endothelial cells binds to the Receptor Activator of Nuclear Factor kappa‐B (RANK) of osteoclast precursors, or vascular smooth muscle cells (VSMCs). This leads to differentiation into mature osteoclasts in the bone, which are involved in bone resorption, whereas in vascular calcification, VSMCs undergo a phenotypic transition into osteochondrogenic cells that can deposit mineralized matrix. Osteoprotegerin (OPG) is the decoy receptor for RANKL, and a potential inhibitor for mineralization
Mentions: Studies assessing the biological and structural changes in aortic valves have predominantly used mouse models. Techniques used have included staining for calcium deposition, quantitative real‐time PCR (qRT‐PCR) to examine changes in mRNA levels for specific genes, protein quantification and enzymatic activity 36. To date, there are reports of pro‐osteogenic signalling cascades thought to contribute to the initiation and progression of aortic stenosis. Signalling molecules include bone morphogenetic proteins (BMPs), Wnt/β‐catenin and transforming growth factor‐β (TGF‐β) although the role of TGF‐β in osteogenic signalling is not clear 36. The RANK/RANKL/OPG pathway is also thought to be involved in the calcification process, which involves complex interactions between receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) (Figure 2) 36, 37. Matrix remodelling may also be involved in the expansion of calcified plaques and pro‐inflammatory processes, through alterations in matrix metalloproteinases (MMPs) and elastin fragments produced by cathepsins 36. Furthermore, the NOTCH1 pathway has been implicated as a regulator of valve calcification, through the repression of the osteoblast transcription factor Runt‐related transcription factor 2 (RUNX2) (Figure 3) 38. This suggests an inhibitory role of NOTCH1 in valvular calcification. Additionally, a number of ECM proteins have been found to have roles in CAVD including collagen, elastin and GAGs, where changes in their expression have impacts on cellular processes, and also cause valve leaflet thickening 39.

Bottom Line: In contrast, large animal models can show considerably greater similarity to humans.Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research.These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, SCT, UK.

No MeSH data available.


Related in: MedlinePlus