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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 NOTCH1 involvement in vascular calcification. NOTCH1 signalling may be involved in the inhibition, as well as the promotion, of vascular calcification through additional factors. Black arrows indicate stimulatory effects, whilst red lines indicate inhibitory effects
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cbf3173-fig-0003: Simplified diagram showing potential NOTCH1 involvement in vascular calcification. NOTCH1 signalling may be involved in the inhibition, as well as the promotion, of vascular calcification through additional factors. Black arrows indicate stimulatory effects, whilst red lines indicate inhibitory effects

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 NOTCH1 involvement in vascular calcification. NOTCH1 signalling may be involved in the inhibition, as well as the promotion, of vascular calcification through additional factors. Black arrows indicate stimulatory effects, whilst red lines indicate inhibitory effects
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4834612&req=5

cbf3173-fig-0003: Simplified diagram showing potential NOTCH1 involvement in vascular calcification. NOTCH1 signalling may be involved in the inhibition, as well as the promotion, of vascular calcification through additional factors. Black arrows indicate stimulatory effects, whilst red lines indicate inhibitory effects
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