Browsing by Author "Han, Richard I."

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    Differential Aortic and Mitral Valve Interstitial Cell Mineralization and the Induction of Mineralization by Lysophosphatidylcholine In Vitro
    (Springer, 2014) Wiltz, Dena C.; Han, Richard I.; Wilson, Reid L.; Kumar, Aditya; Morrisett, Joel D.; Grande-Allen, K. Jane; Bioengineering
    Calcific aortic valve disease (CAVD) is a serious condition with vast uncertainty regarding the precise mechanism leading to valve calcification. This study was undertaken to examine the role of the lipid lysophosphatidylcholine (LPC) in a comparison of aortic and mitral valve cellular mineralization. The proportion of LPC in differentially calcified regions of diseased aortic valves was determined using thin layer chromatography (TLC). Next, porcine valvular interstitial cells (pVICs) from the aortic (paVICs) and mitral valve (pmVICs) were cultured with LPC (10−1–105 nM) and analyzed for cellular mineralization, alkaline phosphatase activity (ALPa), proliferation, and apoptosis. TLC showed a higher percentage of LPC in calcified regions of tissue compared to non-calcified regions. In pVIC cultures, with the exception of 105 nM LPC, increasing concentrations of LPC led to an increase in phosphate mineralization. Increased levels of calcium content were exhibited at 104 nm LPC application compared to baseline controls. Compared to pmVIC cultures, paVIC cultures had greater total phosphate mineralization, ALPa, calcium content, and apoptosis, under both a baseline control and LPC-treated conditions. This study showed that LPC has the capacity to promote pVIC calcification. Also, paVICs have a greater propensity for mineralization than pmVICs. LPC may be a key factor in the transition of the aortic valve from a healthy to diseased state. In addition, there are intrinsic differences that exist between VICs from different valves that may play a key role in heart valve pathology.
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    Morphometric analysis of calcification and fibrous layer thickness in carotid endarterectomy tissues
    (Elsevier, 2016) Han, Richard I.; Wheeler, Thomas M.; Lumsden, Alan B.; Reardon, Michael J.; Lawrie, Gerald M.; Grande-Allen, K. Jane; Morrisett, Joel D.; Brunner, Gerd; Bioengineering
    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 (10 μm 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 patches were found in 20 CEAs (patch size: <0.1mm2 to >1.0mm2). 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 (<0.1 mm2: 0.77±0.01, 0.1–1 mm2: 0.62±0.01, >1.0 mm2: 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.