Abstract 214: Protein Restriction Attenuates Intimal Hyperplasia and Alters Blood Lipid Profiles

Abstract

Introduction Dietary restriction (DR: reduced enteral intake without malnutrition) diminishes the acute phase response to surgical stress in preclinical models. We hypothesized that short-term preoperative protein-free DR would attenuate the vascular response to injury (intimal hyperplasia: IH) while perturbing systemic circulating lipids. Methods After 2 weeks of 60% fat kcal diet, 8 week old B6D2F1/J mice had ad lib access to a complete 10% fat kcal diet (n=10) or a reduced calorie, protein-free diet (DR group, n=10) 1 week before induction of IH, then an ad lib complete diet. IH was induced via a validated model placing a nylon suture tie around the distal carotid artery and external 35g needle mandrel (outer diameter=0.14mm). Subsequent removal of the mandrel created a focal area of stenosis (~78% lumen diameter/~85% flow reduction). 4 weeks later, tissues were harvested for morphology and immunohistochemistry for CD45. Separately, serum was collected from mice fed a complete or DR diet for 1 week absent any surgical stress (n=20/group) for mass spectrometry-based lipidomics. Results DR mice showed less intimal area (p = 0.032) vs controls with statistically equivalent intimal leukocyte infiltration. DR mice also had significantly larger internal elastic lamina length (p = 0.003), a remodeling measure. DR serum exhibited significant decreases in certain classes of circulating lipids, including a collapse of multiple triglyceride types. Conclusions One week of protein-free DR dramatically decreased circulating lipids and attenuated arterial IH. Preoperative dietary manipulations may offer a practical means of extending durability of vascular interventions.