Feasibility of the Assessment of Cholesterol Crystals in Human Macrophages Using Micro Optical Coherence Tomography

The presence of cholesterol crystals is a hallmark of atherosclerosis, but until recently, such crystals have been considered to be passive components of necrotic plaque cores. Recent studies have demonstrated that phagocytosis of cholesterol crystals by macrophages may actively precipitate plaque progression via an inflammatory pathway, emphasizing the need for methods to study the interaction between macrophages and crystalline cholesterol. In this study, we demonstrate the feasibility of detecting cholesterol in macrophages in situ using Micro-Optical Coherence Tomography (µOCT), an imaging modality we have recently developed with 1-µm resolution. Macrophages containing cholesterol crystals frequently demonstrated highly scattering constituents in their cytoplasm on µOCT imaging, and µOCT was able to evaluate cholesterol crystals in cultured macrophage cells. Our results suggest that µOCT may be useful for the detection and characterization of inflammatory activity associated with cholesterol crystals in the coronary artery.

[1]  G. Shipley,et al.  The phase behavior of hydrated cholesterol. , 1979, Journal of lipid research.

[2]  K. Seung,et al.  Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. , 2002, Journal of the American College of Cardiology.

[3]  Nanguang Chen,et al.  Double-reflection polygon mirror for high-speed optical coherence microscopy. , 2007, Optics letters.

[4]  Brett E. Bouma,et al.  In Vivo Characterization of Coronary Atherosclerotic Plaque by Use of Optical Coherence Tomography , 2005, Circulation.

[5]  K. Chu,et al.  Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography , 2013, PloS one.

[6]  Egil Lien,et al.  NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals , 2010, Nature.

[7]  P. Kovanen,et al.  Cholesterol Crystals Activate the NLRP3 Inflammasome in Human Macrophages: A Novel Link between Cholesterol Metabolism and Inflammation , 2010, PloS one.

[8]  P. Bugelski,et al.  Evidence of foam cell and cholesterol crystal formation in macrophages incubated with oxidized LDL by fluorescence and electron microscopy. , 1995, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[9]  Kazushi Takemoto,et al.  Morphology of Exertion-Triggered Plaque Rupture in Patients With Acute Coronary Syndrome: An Optical Coherence Tomography Study , 2008, Circulation.

[10]  G. Ughi,et al.  Standards for Acquisition, Measurement, and Reporting of Intravascular OCT (IVOCT) Studies. A Consensus Report from the International Working Group for Intravascular OCT Standardization and Validation , 2011 .

[11]  Zahi A Fayad,et al.  Progression and Regression of Atherosclerotic Lesions: Monitoring With Serial Noninvasive Magnetic Resonance Imaging , 2002, Circulation.

[12]  Akiko Maehara,et al.  Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. , 2012, Journal of the American College of Cardiology.

[13]  Antonio Colombo,et al.  Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. , 2004, European heart journal.

[14]  S. Haulon,et al.  PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. , 2007, Cell metabolism.

[15]  D. Small,et al.  George Lyman Duff memorial lecture. Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry. , 1988, Arteriosclerosis.

[16]  R D Kamm,et al.  Mechanical properties of model atherosclerotic lesion lipid pools. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[17]  J. Fujimoto,et al.  In vivo endoscopic optical biopsy with optical coherence tomography. , 1997, Science.

[18]  S. Yun,et al.  High-speed optical frequency-domain imaging. , 2003, Optics express.

[19]  E. Halpern,et al.  Characterization of Human Atherosclerosis by Optical Coherence Tomography , 2002, Circulation.

[20]  M. Böhm,et al.  Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model. , 2003, European heart journal.

[21]  Brett E. Bouma,et al.  In vivo association between positive coronary artery remodelling and coronary plaque characteristics assessed by intravascular optical coherence tomography. , 2008, European heart journal.

[22]  Brett E Bouma,et al.  Measurement of collagen and smooth muscle cell content in atherosclerotic plaques using polarization-sensitive optical coherence tomography. , 2007, Journal of the American College of Cardiology.

[23]  E. Halpern,et al.  Quantification of Macrophage Content in Atherosclerotic Plaques by Optical Coherence Tomography , 2003, Circulation.

[24]  Multifactorial Etiology,et al.  George Lyman Duff Memorial Lecture , 1991 .

[25]  K. Moore,et al.  NLRP3 inflamasomes are required for atherogenesis and activated by cholesterol crystals that form early in disease , 2010, Nature.

[26]  Renu Virmani,et al.  Pathology of the vulnerable plaque. , 2007, Journal of the American College of Cardiology.