Protective role for properdin in progression of experimental murine atherosclerosis

Steiner, Tanja, Francescut, Lorenza, Byrne, Simon, Hughes, Timothy Richard ORCID: https://orcid.org/0000-0003-2348-3490, Jayanthi, Archana, Guschina, Irina, Harwood, Adrian John ORCID: https://orcid.org/0000-0003-2377-2612, Cianflone, Katherine, Stover, Cordula and Francis, Sheila 2014. Protective role for properdin in progression of experimental murine atherosclerosis. PLoS ONE 9 (3) , e92404. 10.1371/journal.pone.0092404

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Abstract

Genetic, dietary and immune factors contribute to the pathogenesis of atherosclerosis in humans and mice. Complement activation is an integral part of the innate immune defence but also shapes cellular responses and influences directly triglyceride synthesis. Deficiency of Factor B of the alternative pathway (AP) of complement is beneficial in LDLR−/− mice fed a high fat diet. The serum glycoprotein properdin is a key positive regulator of the AP but has not been studied in experimental atherosclerosis. Atherosclerosis was assessed after feeding low fat (LFD) or high fat (HFD) Western type diets to newly generated LDLR−/− ProperdinKO (LDLR−/−PKO) and LDLR−/−PWT mice. Lipids, lymphocytes and monocytes were similar among genotypes, genders and diets. Complement C3, but not C3adesarg, levels were enhanced in LDLR−/−PKO mice regardless of diet type or gender. Non-esterified fatty acids (NEFA) were decreased in male LDLR−/−PKO fed a HFD compared with controls. All mice showed significant atherosclerotic burden in aortae and at aortic roots but male LDLR−/− mice fed a LFD were affected to the greatest extent by the absence of properdin. The protective effect of properdin expression was overwhelmed in both genders of LDLR−/−mice when fed a HFD. We conclude that properdin plays an unexpectedly beneficial role in the development and progression of early atherosclerotic lesions.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
Additional Information:	2014 Steiner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publisher:	Public Library of Science
ISSN:	1932-6203
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	21 February 2014
Last Modified:	07 May 2023 20:08
URI:	https://orca.cardiff.ac.uk/id/eprint/77339

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