Signaling pathways in mitral valve degeneration

Orton, E. Christopher; Lacerda, Carla M. R.; MacLea, Holly B.

doi:10.1016/j.jvc.2011.12.001

Cited by 60 publications

(56 citation statements)

References 76 publications

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“…This geometry, consistent across a number of mammalian species,8 confers a mechanical advantage and is important for optimizing leaflet curvature, reducing leaflet stress, and maintaining valve competency 8, 9, 10, 11. Differences in MV apparatus morphology and presumably, the mechanical forces acting on the valve have been suggested as a stimulus for signaling pathways that contribute to myxomatous degeneration and its progression 12, 13, 14. Furthermore, abnormal stresses on the MV of dogs have been directly linked in vitro to an increased expression of myxomatous effector proteins 15.…”

Section: Introductionmentioning

confidence: 78%

Comparison of the mitral valve morphologies of Cavalier King Charles Spaniels and dogs of other breeds using 3D transthoracic echocardiography

Menciotti

Borgarelli

Aherne

et al. 2018

Veterinary Internal Medicne

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BackgroundMyxomatous mitral valve disease (MMVD) is more prevalent in Cavalier King Charles Spaniels (CKCSs) compared to dogs of other breeds at a given age. Abnormal valvular stress is thought to contribute to the development and progression of MMVD, and a relationship exists between mitral valve (MV) morphology and stress acting on the valve.ObjectivesTo determine whether the MV morphology of healthy adult CKCSs differs from the morphology of healthy adult dogs of other breeds determined by RT‐3DTTE.AnimalsThirty‐five healthy CKCSs and 41 healthy dogs of other breeds.MethodsProspective cross‐sectional study. Dogs underwent physical examination, conventional echocardiography, and RT‐3DTTE. RT–3DTTE datasets were analyzed using dedicated software for MV morphologic analysis. Morphologic variables were compared between CKCSs and dogs of other breeds.ResultsThe MV of healthy CKCSs had a smaller annulus height (0.46 ± 0.11 vs. 0.56 ± 0.17; P = .0021), tenting height (0.26 ± 0.12 vs. 0.42 ± 0.18; P < .001), tenting area (0.42 ± 0.15 vs. 0.79 ± 0.34; P < .001), normalized tenting volume (0.09 [0.05–0.13] vs. 0.14 [0.10–0.20]; P < .001), and normalized area of the posterior leaflet (0.57 ± 0.15 vs. 0.66 ± 0.18; P = .016) compared to healthy dogs of other breeds; this results in CKCSs having a flatter MV with reduced tenting, compared to the MV of other breeds.Conclusions and Clinical ImportanceThese morphologic features could confer a mechanical disadvantage and play a role in the predisposition of CKCSs to the early development of MMVD.

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Section: Introductionmentioning

confidence: 78%

Comparison of the mitral valve morphologies of Cavalier King Charles Spaniels and dogs of other breeds using 3D transthoracic echocardiography

Menciotti

Borgarelli

Aherne

et al. 2018

Veterinary Internal Medicne

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“…Believed to be normally quiescent, VICs can transition to an activated state to enhance ECM synthesis and degradation [3,4]. Pathological dysregulation of ECM turnover is a major contributor to leaflet dysfunction and disease in both aortic and mitral valves [5,6].…”

Section: Introductionmentioning

confidence: 99%

Differential cell-matrix responses in hypoxia-stimulated aortic versus mitral valves

Sapp¹,

Krishnamurthy²,

Puperi³

et al. 2016

J. R. Soc. Interface.

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Tissue oxygenation often plays a significant role in disease and is an essential design consideration for tissue engineering. Here, oxygen diffusion profiles of porcine aortic and mitral valve leaflets were determined using an oxygen diffusion chamber in conjunction with computational models. Results from these studies revealed the differences between aortic and mitral valve leaflet diffusion profiles and suggested that diffusion alone was insufficient for normal oxygen delivery in mitral valves. During fibrotic valve disease, leaflet thickening due to abnormal extracellular matrix is likely to reduce regional oxygen availability. To assess the impact of low oxygen levels on valve behaviour, whole leaflet organ cultures were created to induce leaflet hypoxia. These studies revealed a loss of layer stratification and elevated levels of hypoxia inducible factor 1-alpha in both aortic and mitral valve hypoxic groups. Mitral valves also exhibited altered expression of angiogenic factors in response to low oxygen environments when compared with normoxic groups. Hypoxia affected aortic and mitral valves differently, and mitral valves appeared to show a stenotic, rheumatic phenotype accompanied by significant cell death. These results indicate that hypoxia could be a factor in mid to late valve disease progression, especially with the reduction in chondromodulin-1 expression shown by hypoxic mitral valves.

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“…The exact molecular mechanisms involved in the initiation and progression of the disease are not fully understood but serotonin (5-hydroxytryptamine, 5-HT) is suggested to be involved in the pathogenesis (Orton et al, 2012;Oyama and Levy, 2010). Tissue studies from dogs have shown increased expression of 5-HT2BR in myxomatous mitral valves (Disatian and Orton, 2009;Oyama and Chittur, 2006), and tryptophan hydroxylase-1 (TPH1), the ratelimiting enzyme in 5-HT synthesis, was increased in early as well as late stage disease (Disatian et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Alpha-smooth muscle actin and serotonin receptors 2A and 2B in dogs with myxomatous mitral valve disease

Cremer

Moesgaard

Rasmussen

et al. 2015

Research in Veterinary Science

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Signaling pathways in mitral valve degeneration

Cited by 60 publications

References 76 publications

Comparison of the mitral valve morphologies of Cavalier King Charles Spaniels and dogs of other breeds using 3D transthoracic echocardiography

Comparison of the mitral valve morphologies of Cavalier King Charles Spaniels and dogs of other breeds using 3D transthoracic echocardiography

Differential cell-matrix responses in hypoxia-stimulated aortic versus mitral valves

Alpha-smooth muscle actin and serotonin receptors 2A and 2B in dogs with myxomatous mitral valve disease

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