Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation.
Cardiovascular disease is the leading cause of morbidity and mortality in the world. Atherosclerotic plaques, consisting of lipid-laden macrophages and calcification, develop in the coronary arteries, aortic valve, aorta, and peripheral conduit arteries and are the hallmark of cardiovascular disease. In humans, imaging with computed tomography allows for the quantification of vascular calcification; the presence of vascular calcification is a strong predictor of future cardiovascular events. Development of novel therapies in cardiovascular disease relies critically on improving our understanding of the underlying molecular mechanisms of atherosclerosis. Advancing our knowledge of atherosclerotic mechanisms relies on murine and cell-based models. Here, a method for imaging aortic calcification and macrophage infiltration using two spectrally distinct near-infrared fluorescent imaging probes is detailed. Near-infrared fluorescent imaging allows for the ex vivo quantification of calcification and macrophage accumulation in the entire aorta and can be used to further our understanding of the mechanistic relationship between inflammation and calcification in atherosclerosis. Additionally, a method for isolating and culturing animal aortic vascular smooth muscle cells and a protocol for inducing calcification in cultured smooth muscle cells from either murine aortas or from human coronary arteries is described. This in vitro method of modeling vascular calcification can be used to identify and characterize the signaling pathways likely important for the development of vascular disease, in the hopes of discovering novel targets for therapy.
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital.
Caitlin
C
O'Rourke
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital.
Georgia
G
Shelton
Cardiovascular Division, Brigham and Women's Hospital; Harvard Medical School.
Joshua D
JD
Hutcheson
Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital.
Megan F
MF
Burke
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital.
Trejeeve
T
Martyn
Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital.
Timothy E
TE
Thayer
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital.
Hannah R
HR
Shakartzi
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital.
Mary D
MD
Buswell
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital.
Robert E
RE
Tainsh
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Harvard Medical School.
Binglan
B
Yu
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Harvard Medical School.
Aranya
A
Bagchi
Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital; Harvard Medical School.
David K
DK
Rhee
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital; Harvard Medical School.
Connie
C
Wu
Department of Anesthesiology, Uniklinik RWTH Aachen, RWTH Aachen University.
Matthias
M
Derwall
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Harvard Medical School.
Emmanuel S
ES
Buys
Cardiovascular Division, Brigham and Women's Hospital; Harvard Medical School.
Paul B
PB
Yu
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital; Harvard Medical School.
Kenneth D
KD
Bloch
Cardiovascular Division, Brigham and Women's Hospital; Harvard Medical School.
Elena
E
Aikawa
Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Department of Anesthesiology, Uniklinik RWTH Aachen, RWTH Aachen University; Center for Immunology and Inflammatory Diseases and the Division of Rheumatology, Allergy, and Immunology of the Department of Medicine, Massachusetts General Hospital.
Donald B
DB
Bloch
Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital; Harvard Medical School; rmalhotra@mgh.harvard.edu.
Rajeev
R
Malhotra
D000818:Animals; D001018:Aortic Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D002114:Calcinosis / Q000000981:diagnostic imaging*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007249:Inflammation; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology