Elizabeth Le Master1, Ibra S Fancher2, James Lee3, Irena Levitan4. 1. Division of Pulmonary and Critical Care, Department of Medicine, University of Illinois at Chicago, United States; Bioengineering, University of Illinois at Chicago, United States. 2. Division of Pulmonary and Critical Care, Department of Medicine, University of Illinois at Chicago, United States. 3. Bioengineering, University of Illinois at Chicago, United States. 4. Division of Pulmonary and Critical Care, Department of Medicine, University of Illinois at Chicago, United States; Bioengineering, University of Illinois at Chicago, United States. Electronic address: levitan@uic.edu.
Abstract
OBJECTIVE: To perform comparative analysis of the role of scavenger receptor CD36 on endothelial vs. sub-endothelial elastic modulus (stiffness) in the aortas of young and aged mice. APPROACHES AND RESULTS: Elastic moduli of endothelial and sub-endothelial layers of freshly isolated mouse aortas were quantified using atomic force microscopy. In young mice (4-6 months old), we found that while endothelial stiffness is markedly reduced in aortas of CD36-/-mice, as compared to WT controls, no difference between CD36-/- and WT aortas is observed in the stiffness of the sub-endothelial layer in denuded arteries. Additionally, inhibition of myosin phosphorylation also decreases the elastic modulus in the EC, but not the sub-EC layer in WT mice. Moreover, inhibiting CD36 mediated uptake of oxLDL in intact WT aortas abrogated oxLDL-induced endothelial stiffening. Further analysis of aged mice (22-25 months) revealed that aging resulted not only in significant stiffening of the denuded arteries, as was previously known, but also a comparable increase in the elastic modulus of the endothelial layer. Most significantly, this stiffening in the EC layer is dependent on CD36, whereas the denuded layer is not affected. CONCLUSIONS: Our results show that the role CD36 in stiffening of cellular components of intact aortas is endothelial-specific and that genetic deficiency of CD36 protects against endothelial stiffening in aged mice. Moreover, these data suggest that endothelial stiffness in intact mouse aortas depends more on the expression of CD36 than on the stiffness of the sub-endothelial layer.
OBJECTIVE: To perform comparative analysis of the role of scavenger receptor CD36 on endothelial vs. sub-endothelial elastic modulus (stiffness) in the aortas of young and aged mice. APPROACHES AND RESULTS: Elastic moduli of endothelial and sub-endothelial layers of freshly isolated mouse aortas were quantified using atomic force microscopy. In young mice (4-6 months old), we found that while endothelial stiffness is markedly reduced in aortas of CD36-/-mice, as compared to WT controls, no difference between CD36-/- and WT aortas is observed in the stiffness of the sub-endothelial layer in denuded arteries. Additionally, inhibition of myosin phosphorylation also decreases the elastic modulus in the EC, but not the sub-EC layer in WT mice. Moreover, inhibiting CD36 mediated uptake of oxLDL in intact WT aortas abrogated oxLDL-induced endothelial stiffening. Further analysis of aged mice (22-25 months) revealed that aging resulted not only in significant stiffening of the denuded arteries, as was previously known, but also a comparable increase in the elastic modulus of the endothelial layer. Most significantly, this stiffening in the EC layer is dependent on CD36, whereas the denuded layer is not affected. CONCLUSIONS: Our results show that the role CD36 in stiffening of cellular components of intact aortas is endothelial-specific and that genetic deficiency of CD36 protects against endothelial stiffening in aged mice. Moreover, these data suggest that endothelial stiffness in intact mouse aortas depends more on the expression of CD36 than on the stiffness of the sub-endothelial layer.
Authors: Tzu Pin Shentu; Igor Titushkin; Dev K Singh; Keith J Gooch; Papasani V Subbaiah; Michael Cho; Irena Levitan Journal: Am J Physiol Cell Physiol Date: 2010-04-21 Impact factor: 4.249
Authors: Madhu S Gundavaram; Tzu Pin Shentu; Gregory B Kowalsky; Suncica Volkov; Dean E Schraufnagel; Irena Levitan Journal: Pulm Circ Date: 2013-12-05 Impact factor: 3.017
Authors: Elizabeth Le Master; Ru-Ting Huang; Chongxu Zhang; Yedida Bogachkov; Cassandre Coles; Tzu-Pin Shentu; Yue Sheng; Ibra S Fancher; Carlos Ng; Theodore Christoforidis; Pappasani V Subbaiah; Evgeny Berdyshev; Zhijian Qain; David T Eddington; James Lee; Michael Cho; Yun Fang; Richard D Minshall; Irena Levitan Journal: Arterioscler Thromb Vasc Biol Date: 2017-10-12 Impact factor: 8.311
Authors: Caitlin Collins; Lukas D Osborne; Christophe Guilluy; Zhongming Chen; E Tim O'Brien; John S Reader; Keith Burridge; Richard Superfine; Ellie Tzima Journal: Nat Commun Date: 2014-06-11 Impact factor: 14.919
Authors: Anna Garcia-Sabaté; Walaa Kamal E Mohamed; Jiranuwat Sapudom; Aseel Alatoom; Layla Al Safadi; Jeremy C M Teo Journal: Bioengineering (Basel) Date: 2020-09-16
Authors: Megan Lee; Kevin Chu; Mainak Chakraborty; Nicholas Kotoulas; Masoud Akbari; Cynthia Goh; Xavier Clemente-Casares; Daniel A Winer; Annie Shrestha; Sue Tsai Journal: STAR Protoc Date: 2022-03-17
Authors: Marwa Mahmoud; Mariya Mayer; Limary M Cancel; Anne Marie Bartosch; Rick Mathews; John M Tarbell Journal: Cardiovasc Res Date: 2021-05-25 Impact factor: 10.787