Reconstituted high-density lipoproteins promote wound repair and blood flow recovery in response to ischemia in aged mice

Tsatralis, T., Ridiandries, A., Robertson, S., Vanags, L. Z., Lam, Y. T., Tan, J. T. M., Ng, M. K. C. and Bursill, C. A. (2016) Reconstituted high-density lipoproteins promote wound repair and blood flow recovery in response to ischemia in aged mice. Lipids in Health and Disease, 15, 150. (doi: 10.1186/s12944-016-0322-4) (PMID:27600523) (PMCID:PMC5012086)

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Abstract

Background: The average population age is increasing and the incidence of age-related vascular complications is rising in parallel. Impaired wound healing and disordered ischemia-mediated angiogenesis are key contributors to age-impaired vascular complications that can lead to amputation. High-density lipoproteins (HDL) have vasculo-protective properties and augment ischemia-driven angiogenesis in young animals. We aimed to determine the effect of reconstituted HDL (rHDL) on aged mice in a murine wound healing model and the hindlimb ischemia (HLI) model. Methods: Murine wound healing model—24-month-old aged mice received topical application of rHDL (50 μg/wound/ day) or PBS (vehicle control) for 10 days following wounding. Murine HLI model—Femoral artery ligation was performed on 24-month-old mice. Mice received rHDL (40 mg/kg) or PBS, intravenously, on alternate days, 1 week pre-surgery and up to 21 days post ligation. For both models, blood flow perfusion was determined using laser Doppler perfusion imaging. Mice were sacrificed at 10 (wound healing) or 21 (HLI) days post-surgery and tissues were collected for histological and gene analyses. Results: Daily topical application of rHDL increased the rate of wound closure by Day 7 post-wounding (25 %, p < 0.05). Wound blood perfusion, a marker of angiogenesis, was elevated in rHDL treated wounds (Days 4–10 by 22–25 %, p < 0. 05). In addition, rHDL increased wound capillary density by 52.6 %. In the HLI model, rHDL infusions augmented blood flow recovery in ischemic limbs (Day 18 by 50 % and Day 21 by 88 %, p < 0.05) and prevented tissue necrosis and toe loss. Assessment of capillary density in ischemic hindlimb sections found a 90 % increase in rHDL infused animals. In vitro studies in fibroblasts isolated from aged mice found that incubation with rHDL was able to significantly increase the key pro-angiogenic mediator vascular endothelial growth factor (VEGF) protein (25 %, p < 0.05). Conclusion: rHDL can promote wound healing and wound angiogenesis, and blood flow recovery in response to ischemia in aged mice. Mechanistically, this is likely to be via an increase in VEGF. This highlights a potential role for HDL in the therapeutic modulation of age-impaired vascular complications.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robertson, Dr Stacy
Authors: Tsatralis, T., Ridiandries, A., Robertson, S., Vanags, L. Z., Lam, Y. T., Tan, J. T. M., Ng, M. K. C., and Bursill, C. A.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Lipids in Health and Disease
Publisher:BioMed Central
ISSN:1476-511X
ISSN (Online):1476-511X
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Lipids in Health and Disease 15: 150
Publisher Policy:Reproduced under a Creative Commons license

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