Differential Aortic and Mitral Valve Interstitial Cell Mineralization and the Induction of Mineralization by Lysophosphatidylcholine In Vitro

Wiltz, Dena C.; Han, Richard I.; Wilson, Reid; Kumar, Aditya; Morrisett, Joel D.; Grande-Allen, K. Jane

doi:10.1007/s13239-014-0197-3

Cited by 18 publications

(13 citation statements)

References 55 publications

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“…undergo significant fibrotic remodelling with a breakdown of the layered structure [6,15]. Despite their mutual ability to calcify, it has been proposed that aortic and mitral valves exhibit different osteogenic potentials in culture [16]. Interestingly, pathways involved in CAVD in aortic valves may lead to MMVD instead of MS in mitral valves [17].…”

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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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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“…The oxidized phospholipid molecules are bounded to lipoprotein(a), which is the major phospholipids carrier, mentioned also as the risk factor responsible for the significant increase of matrix vesicles formation, elevated alkaline phosphatase activity and calcification process of HAVICs . In the valve tissue during the lipolysis by lipoprotein‐associated phospholipase A 2 , oxidized phosphatidylcholine is converted into lysophosphatidylcholine, which impacts on HAVICs' mineralization in vitro . Its effect was also tested on vascular SMCs, proving the induction of osteogenic morphology, physiology, and gene expression, which may be a contributing factor to the formation of calcifying vascular cells .…”

Section: Resultsmentioning

confidence: 99%

Phospholipids accumulation and calcification in cultured primary human aortic valve interstitial cells: New insights revealed by confocal Raman imaging

Czamara

Kopytek

Szulczewska

et al. 2019

J Raman Spectroscopy

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Raman imaging was applied to investigate calcification process in situ in primary human aortic valve interstitial cells (HAVICs) isolated from patients with developed non-rheumatic aortic stenosis (AS). To invoke calcification, cells were incubated in an osteogenic medium (OSM) in some cases supplemented with glucose. Surprisingly, upon 7 days of incubation, no calcification in the form of inorganic salts was detected, instead, the increase of lipid inclusions containing phospholipids inside HAVICs was observed, probably in the sites involved in further mineral precipitation. Glucose supplementation (reflecting diabetes mellitus influence on AS) slightly decreased the overall content of phospholipids. A long incubation time resulted in the formation of significant amounts of inorganic calcium salts extracellularly and only in the presence of type I collagen. In the absence of type I collagen, calcium oxalate dihydrate was observed inside the cells. Due to application of Raman imaging, an unbiased, label-free method of high-spatial resolution and chemical specificity, it was possible to demonstrate unequivocally that calcification in the form of hydroxyapatite took place extracellularly in the presence of type I collagen and required long incubation with OSM.

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“…The accumulation of cholesteryl ester in low-density lipoprotein (LDL) particles is a hallmark of atherosclerosis. Over time oxidized-LDL (oxLDL) and lysophosphatidylcholine can promote calcification in vascular interstitial cells (9, 17). Advanced atherosclerotic plaques are characterized by the formation of a fibrous cap which encages the lipid core atheroma and the presence of calcification which results from the deposition of calcium phosphate crystals (typically as hydroxyapatite) in the vessel wall.…”

Section: Discussionmentioning

confidence: 99%

Morphometric analysis of calcification and fibrous layer thickness in carotid endarterectomy tissues

Han

Lumsden

Reardon

et al. 2016

Computers in Biology and Medicine

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Background Advanced atherosclerotic lesions are commonly characterized by the presence of calcification. Several studies indicate that extensive calcification is associated with plaque stability, yet recent studies suggest that calcification morphology and location may adversely affect the mechanical stability of atherosclerotic plaques. The underlying cause of atherosclerotic calcification and the importance of intra-plaque calcium distribution remains poorly understood. Method The goal of this study was the characterization of calcification morphology based on histological features in 20 human carotid endarterectomy (CEA) specimens. Representative frozen sections (10μm thick) were cut from the common, bulb, internal and external segments of CEA tissues and stained with von Kossa’s reagent for calcium phosphate. The morphology of calcification (calcified patches) and fibrous layer thickness were quantified in 135 histological sections. Results Intra-plaque calcification was distributed heterogeneously (calcification %-area: bulb segment: 14.2±2.1%; internal segment: 12.9±2.8%; common segment: 4.6±1.1%; p=0.001). Calcified patch sizes ranged from <0.1mm2 to >1.0mm2, and were found in 20 CEAs. Calcified patches were most abundant in the bulb and least in the common segment (bulb n=7.30±1.08; internal n=4.81±1.17; common n=2.56±0.56; p=0.0007). Calcified patch circularity decreased with increasing size (<0.1mm2=0.77±0.01, 0.1–1mm2=0.62±0.01, >1.0mm2=0.51±0.02; p=0.0001). A reduced fibrous layer thickness was associated with increased calcium patch size (p<0.0001). Conclusions In advanced carotid atherosclerosis, calcification appears to be a heterogeneous and dynamic atherosclerotic plaque component, as indicated by the simultaneous presence of few large stabilizing calcified patches and numerous small calcific patches. Future studies are needed to elucidate the associations of intra-plaque calcification size and distribution with atherothrombotic events.

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Differential Aortic and Mitral Valve Interstitial Cell Mineralization and the Induction of Mineralization by Lysophosphatidylcholine In Vitro

Cited by 18 publications

References 55 publications

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

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

Phospholipids accumulation and calcification in cultured primary human aortic valve interstitial cells: New insights revealed by confocal Raman imaging

Morphometric analysis of calcification and fibrous layer thickness in carotid endarterectomy tissues

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