Richard I Han1, Thomas M Wheeler2, Alan B Lumsden3, Michael J Reardon3, Gerald M Lawrie3, K Jane Grande-Allen4, Joel D Morrisett5, Gerd Brunner6. 1. Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, United States; Department of Bioengineering, Rice University, Houston, TX, United States. 2. Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, United States. 3. Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX, United States. 4. Department of Bioengineering, Rice University, Houston, TX, United States. 5. Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, United States. 6. Division of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX, United States; Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX, United States. Electronic address: gbrunner@bcm.edu.
Abstract
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 patches were found in 20 CEAs (patch size: <0.1mm(2) to >1.0mm(2)). 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 (<0.1mm(2): 0.77±0.01, 0.1-1mm(2): 0.62±0.01, >1.0mm(2): 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.
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 patches were found in 20 CEAs (patch size: <0.1mm(2) to >1.0mm(2)). 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 (<0.1mm(2): 0.77±0.01, 0.1-1mm(2): 0.62±0.01, >1.0mm(2): 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.
Authors: Bashar Ababneh; Loui Rejjal; Yashashwi Pokharel; Vijay Nambi; Xukui Wang; Ching-Hsuan Tung; Richard I Han; Addison A Taylor; Panagiotis Kougias; Alan B Lumsden; Gerald Lawrie; Michael Reardon; Christie M Ballantyne; Joel D Morrisett; Gerd Brunner Journal: Vasc Med Date: 2014-09-05 Impact factor: 3.239
Authors: Kasey C Vickers; Colin T Maguire; Robert Wolfert; Alan R Burns; Michael Reardon; Richard Geis; Paul Holvoet; Joel D Morrisett Journal: J Lipid Res Date: 2009-04-09 Impact factor: 5.922
Authors: Wael E Shaalan; Hongwei Cheng; Bruce Gewertz; James F McKinsey; Lewis B Schwartz; Daniel Katz; Dindcai Cao; Tina Desai; Seymour Glagov; Hisham S Bassiouny Journal: J Vasc Surg Date: 2004-08 Impact factor: 4.268
Authors: Richard I Han; Chenyue W Hu; David S Loose; Li Yang; Li Li; Jennifer P Connell; Michael J Reardon; Gerald M Lawrie; Amina A Qutub; Joel D Morrisett; K Jane Grande-Allen Journal: Heart Vessels Date: 2021-11-02 Impact factor: 2.037
Authors: Mircea Catalin Cosarca; Emőke Horváth; Calin Molnar; Gyopár-Beáta Molnár; Eliza Russu; Vasile Adrian Mureșan Journal: Exp Ther Med Date: 2021-06-11 Impact factor: 2.447