Abstract
Drug-induced vascular injury (DIVI), defined as arterial medial degeneration/necrosis usually associated with perivascular inflammation, is frequently observed in the mesenteric arteries of rats but the relevance to humans remains a hurdle for drug development. Here, we describe the evaluation of commercially available optical imaging biomarkers using a rat DIVI model. Male Sprague Dawley rats were administered 10 mg/kg/day of a proprietary soluble guanylate cyclase activator (sGCa). Optical agents, AngioSense for the detection of vessel permeability, MMPSense for the detection of activated matrix metalloproteinases (MMPs), and IntegriSense for the detection of αvβ3 integrin, were injected via tail vein 24 hours before fluorescence (FL) ex vivo imaging. Imaging found a statistically significant difference in FL from all optical agents between treated and vehicle groups (p < .05). Mesenteric arteries were further analyzed by histopathology, flow cytometry, and immunohistochemistry. Histopathology confirmed perivascular inflammation and/or arterial medial degeneration in the sGCa-treated animals. Flow cytometry of digested arteries revealed myeloid cells as a main source of MMPSense signal. Immunohistochemical analysis further id...Continue Reading
References
Jan 1, 1989·Toxicologic Pathology·W D KernsD G Morgan
Dec 15, 1987·Biochemical Pharmacology·P J BoorG A Ansari
Dec 1, 1994·The Journal of Clinical Investigation·Z S GalisP Libby
Jul 1, 1994·Circulation Research·Z S GalisP Libby
Sep 1, 1994·Circulation Research·M P BendeckM A Reidy
Jan 1, 1995·Archives of Toxicology·G HantonB Leblanc
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·I HalpertW C Parks
Mar 14, 1998·Toxicology and Applied Pharmacology·D J Conklin, P J Boor
Mar 2, 1999·The Journal of Experimental Medicine·U SchönbeckP Libby
May 20, 1999·Circulation·G K SukhovaP Libby
Jun 24, 2004·Circulation·Mehran M SadeghiJeffrey R Bender
Jun 25, 2004·The American Journal of Pathology·Alexander S AntonovRoss G Gerrity
Aug 3, 2004·Nature Reviews. Immunology·William C ParksYolanda S López-Boado
Dec 25, 2004·Physiological Reviews·Andrew C Newby
Apr 22, 2005·The New England Journal of Medicine·Göran K Hansson
Nov 4, 2005·Cardiovascular Research·Andrew C Newby
Jun 17, 2006·Nature Reviews. Immunology·Göran K Hansson, Peter Libby
Sep 7, 2006·Nature Reviews. Drug Discovery·Oleg V EvgenovJohannes-Peter Stasch
Mar 7, 2007·Expert Review of Cardiovascular Therapy·Jason Lee Johnson
Aug 8, 2007·Journal of Vascular Surgery·Taku KokuboEric T Choi
Sep 6, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Andrew C Newby
Jan 13, 2010·Circulation·Dieter GronebergAndreas Friebe
Jun 17, 2010·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Gerrit L ten KateArend F L Schinkel
Aug 7, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Kiyuk ChangFarouc A Jaffer
May 19, 2011·Molecular Cancer Therapeutics·Qingbei ZhangH Rosie Xing
Sep 29, 2011·Arthritis and Rheumatism·Paul A MonachPeter A Merkel
Nov 3, 2012·International Journal of Molecular Imaging·Shu-An LinBohumil Bednar
Citations
Aug 10, 2017·PloS One·Jen-Chieh TsengJeffrey D Peterson
Feb 24, 2016·Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada·Darren G HaskettJonathan P Vande Geest
Aug 10, 2019·Stem Cells and Development·Drew M TitmarshSimon M Cool
Nov 26, 2015·PloS One·Taemoon ChungJune-Key Chung
Aug 24, 2017·Toxicologic Pathology·Raymond J GonzalezWarren E Glaab
Oct 27, 2021·Head & Neck·Melanie D HicksCarissa M Thomas