In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
Abstract:
Objective: Short-term protein restriction (PR) preceding surgery limits ischemia reperfusion injury and arterial intimal hyperplasia in mouse models, possibly via upregulation of endogenous enzymatic production of the gaseous messenger hydrogen sulfide (H 2 S) by cystathionine-gamma-lyase (CGL). Here, we tested the hypothesis that short-term PR will limit vein graft disease (VGD) via CGL upregulation and increased H 2 S production, resulting in EC cytoprotection and reduced leukocyte transmigration. Approach and Results: LDLR -\- mice (male, 8-10 weeks old) were fed a high fat/high cholesterol (HF/HC) diet for two weeks. One group was then switched to a PR HF/HC diet with or without daily CGL inhibitor propargylglycine (PAG) injections. 7 days later mice underwent carotid interposition grafting with donor caval veins from mice on matched diets. Mice were euthanized at baseline (preop), post-op day 4 or 28 for analysis of the graft (histology, immunohistochemistry), aorta (western blot) and kidney EC (flow-cytometry). PR mice showed decreased graft intimal/media+adventitia (I/M+A) area and thickness ratios (Fig. A) on post-op day 28. Staining for CD31 and neutrophil-elastase revealed a relatively intact EC layer (Fig. B-C, CD31 in brown, red arrows, p 〈 0.001) and less neutrophil transmigration (p=0.02) on post-op day 4. PR increased baseline CGL expression in aortas (Fig. D-E) and upregulated EC H 2 S (Fig. F). Our preliminary data indicates that PAG injections during PR tended to diminish its protective effects on VGD (Fig. G). Conclusions: PR attenuated VGD via limiting of EC damage concomitant with increased CGL expression and endogenous H 2 S production. Ongoing studies will further define the CGL dependence of this process. Short-term preoperative PR stands as a potentially simple, safe, cost-efficient intervention to enhance vein graft durability.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.38.suppl_1.337
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2018
detail.hit.zdb_id:
1494427-3
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