Premium
A novel estimate of endothelial cell autophagic flux is associated with greater vascular endothelial function and reduced oxidative stress in healthy middle‐aged/older adults (855.3)
Author(s) -
Boekel Anna,
SantosParker Jessica,
LaRocca Thomas,
Seals Douglas,
Kaplon Rachelle
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.855.3
Subject(s) - autophagy , brachial artery , oxidative stress , endothelial dysfunction , endothelium , vasodilation , medicine , endocrinology , chemistry , biochemistry , blood pressure , apoptosis
Using only indirect, static markers of the dynamic cellular quality control system, autophagy, we have reported impaired autophagy in biopsied vascular endothelial cells (EC) of humans with aging that is related to endothelial dysfunction, as indicated by reduced endothelium‐dependent dilation (EDD), and oxidative stress. Here, we estimated dynamic autophagic flux in EC from 10 healthy adults aged 51‐73 by calculating the within‐subject difference in the expression of microtubule‐associated protein light chain 3 (LC3 ratio) between ECs incubated in the absence vs. presence of chloroquine (50 μM 1.5 hrs) to inhibit autophagy. EDD was assessed by: 1) brachial artery flow‐mediated dilation (FMD); and 2) forearm blood flow (FBF) to incremental brachial artery infusions of acetylcholine. Oxidative stress‐suppression of EDD was determined by ∆FBF to co‐infusion of vitamin C (vitC). The LC3 ratio was positively related to FMD (r=0.76, P<0.05) and FBF (r=0.56, P<0.05), but not endothelium‐independent dilation to NO donors (both P>0.05). The LC3 ratio also was inversely related to ∆FBF with vitC (r=‐0.57, P<0.05). These findings provide novel evidence that greater EC autophagic flux is associated with improved endothelial function linked to reduced oxidative stress in healthy middle‐aged/older adults. Grant Funding Source : NIH AG044031 TR001082 AG013038