title: Chemotherapy-induced vascular toxicity--real-time in vivo imaging of vessel impairment.
abstract: Certain classes of chemotherapies may exert acute vascular changes that may progress into long-term conditions that may predispose the patient to an increased risk of vascular morbidity. Yet, albeit the mounting clinical evidence, there is a paucity of clear studies of vascular toxicity and therefore the etiology of a heterogeneous group of vascular/cardiovascular disorders remains to be elucidated. Moreover, the mechanism that may underlie vascular toxicity can completely differ from the principles of chemotherapy-induced cardiotoxicity, which is related to direct myocyte injury. We have established a real-time, in vivo molecular imaging platform to evaluate the potential acute vascular toxicity of anti-cancer therapies. We have set up a platform of in vivo, high-resolution molecular imaging in mice, suitable for visualizing vasculature within confined organs and reference blood vessels within the same individuals whereas each individual serve as its own control. Blood vessel walls were impaired after doxorubicin administration, representing a unique mechanism of vascular toxicity that may be the early event in end-organ injury. Herein, the method of fibered confocal fluorescent microscopy (FCFM) based imaging is described, which provides an innovative mode to understand physiological phenomena at the cellular and sub-cellular levels in animal subjects.
authors.affiliation: Department of Cell and Developmental Biology, Tel Aviv University; Sackler Faculty of Medicine, Tel Aviv University.
authors.forename: Hadas
authors.initials: H
authors.lastname: Bar-Joseph
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University; Institute of Oncology, Davidoff Center and Rabin Medical Center.
authors.forename: Salomon Marcello
authors.initials: SM
authors.lastname: Stemmer
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University; Department of Clinical Microbiology and Immunology, Tel Aviv University.
authors.forename: Ilan
authors.initials: I
authors.lastname: Tsarfaty
authors.affiliation: Department of Cell and Developmental Biology, Tel Aviv University; Sackler Faculty of Medicine, Tel Aviv University.
authors.forename: Ruth
authors.initials: R
authors.lastname: Shalgi
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University; Institute of Oncology, Davidoff Center and Rabin Medical Center; iritbenaharon@gmail.com.
authors.forename: Irit
authors.initials: I
authors.lastname: Ben-Aharon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D003199:Computer Systems; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D005269:Femur / Q000098:blood supply; D051379:Mice; D008813:Mice, Inbred ICR; D008833:Microcirculation / Q000187:drug effects; D018613:Microscopy, Confocal / Q000379:methods*; D014652:Vascular Diseases / Q000139:chemically induced* / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin