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Increased Oxidative Stress Modulates Coronary Artery Remodeling and Passive Stiffness in db/db Diabetic Mice
Author(s) -
Katz Paige S,
Rocic Petra,
Souza Flavia M,
Matrougui Khalid,
Lord Kevin C,
Lucchesi Pamela A
Publication year - 2007
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.21.6.a1379-c
Subject(s) - oxidative stress , medicine , endocrinology , arterial stiffness , myograph , cardiology , ventricular remodeling , artery , chemistry , myocardial infarction , blood pressure
Alterations in coronary artery (CA) structure regulate arterial stiffness and may lead to decreased cardiac perfusion and coronary flow reserve. Although oxidative stress affects coronary pathology, its contribution to vascular remodeling in diabetes is undefined. This study established a link between oxidative stress and CA remodeling and stiffness. Coronary arteries (<100 μ) from heterozygous (Db/db) and diabetic (db/db) mice at ages 8–16 wks were isolated and mounted on a pressure myograph for measurement of structural and passive mechanical properties. Mean arterial pressure (MAP) was monitored by telemetry. DHE staining was used as a marker for oxidative stress. NAD(P)H oxidase subunits and MnSOD expression was assessed by real time RT‐PCR and immunohistochemistry. No changes in MAP between groups were observed. Increased DHE staining was observed in 12 wk db/db mice vs. Db/db and was associated with increased mRNA expression and staining for the NAD(P)H oxidase Nox1 and gp91phox subunits and decreased MnSOD. Significant inward remodeling was not detected until 16 wks in the db/db vs. Db/db, defined by decreased lumen:media ratio (29±6 vs. 12±2%) and compliance and increased remodeling index (46±5%) and passive stiffness. In vivo treatment with TEMPOL (10 mM in the drinking water from 8–16 wks) reduced DHE staining and attenuated inward remodeling of db/db CA. These data suggest that increased oxidative stress is critical for altered structural and functional remodeling of CA in Type 2 diabetes. Supported by HL56046 and P20RR18766.