Strawberry Supplementation Lessens Vascular Inflammation and Dysfunction Displayed by Diabetic db/db Mice

Abstract

BackgroundCardiovascular disease is 2–4 fold more prevalent in patients with diabetes. In diabetes high glucose induced vascular inflammation and the subsequent endothelial dysfunction leads to the development of atherosclerosis. Human studies have shown that the consumption of strawberries (SB) improves cardiovascular risk but the effects of SB on diabetic vasculature are unknown. We sought to determine whether dietary strawberry supplementation attenuates vascular inflammation and dysfunction in diabetic db/db mice.MethodsSeven‐week old male diabetic db/db mice that consumed standard chow (db/db) or chow supplemented with 2.35% freeze‐dried strawberries (db/db+SB) for 10 weeks were compared to non‐diabetic control mice (db/+). Based on normalization to body surface area, the SB dose is equivalent to two human servings of SB (~160 g) per day. In vivo assessments at ~17 weeks included body weight and food intake, glucose (GTT), and insulin (ITT) tolerance, and systemic arterial blood pressure (tail cuff). Ex vivo analyses included arterial inflammation (monocyte binding to aortic endothelium), endothelial cell (EC) inflammation (mRNA expression of inflammatory cytokines in carotid artery ECs), and mesenteric arterial reactivity (isometric tension procedures).ResultsCompared to db/+ animals, both diabetic groups displayed similar increases (p<0.05) in weight gain and impairments (p<0.05) in glucose and insulin tolerance. Arterial pressure (systolic, diastolic, and mean) was higher (p<0.05) in db/db vs. db/+ mice, but the severity of hypertension was attenuated (p<0.05) in db/db+SB mice. Relaxation to acetylcholine (ACh; 10−8‐10−6 M) in arteries precontracted with ~ 10−6 M phenylephrine was impaired (p<0.05) in db/db mice vs. db/+ animals, but no differences existed between db/db+SB vs. db/+ mice. Vasorelaxation to sodium nitroprusside (10−9‐10−4 M) was complete and similar among groups. Mouse monocyte WEHI 78/24 cells exhibited higher (p<0.05) binding to the aortic endothelium of db/db vs. db/+ mice, but this response was attenuated (p<0.05) in aortic endothelium from db/db+SB mice. Consistent with these findings, relative to results obtained from db/+ animals, elevations of MCP‐1/JE and KC expression were greater (p<0.05) in carotid artery ECs from db/db but were suppressed in db/db+SB mice.ConclusionDietary supplementation of strawberries attenuates indices of diabetes‐induced vascular dysfunction without altering glucose and insulin tolerance. This study provides proof of concept for further considering strawberries as an adjunct therapy to improving vascular complications associated with diabetes.Support or Funding InformationSupported by University of Utah Seed Grant and the College of Health Research Pilot Grant.