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Role of NAD(P)H Oxidase‐ and Mitochondria‐derived ROS in Coronary Collateral Growth
Author(s) -
Rocic Petra,
Chilian William M
Publication year - 2008
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.22.1_supplement.524.5
Subject(s) - nad(p)h oxidase , apocynin , nad+ kinase , chemistry , oxidase test , oxidative stress , nadph oxidase , mitochondrion , arteriogenesis , medicine , endocrinology , ischemia , biochemistry , enzyme
Relative importance of NAD(P)H oxidase‐ vs. mitochondria (mt)‐derived oxidative stress (OxStress) in cardiovascular pathologies, including impaired arteriogenesis, is unresolved. We investigated the contribution both to regulation of coronary collateral growth (CCG). CCG was stimulated in lean Zucker (LZR) and prediabetic obese Zucker (ZOF), where OxStress is elevated, rats by repetitive ischemia (RI). Coronary blood flow was measured in normal (NZ) and collateral‐dependent (CZ) zones. RI increased CZ flow (0.23 to 0.84 ml/min/g; CZ/NZ 0.84 ± 0.03) in LZR, but failed to increase it in ZOF (0.08 to 0.15 ml/min/g; CZ/NZ 0.16 ± 0.03). Treatment with a ubiquitous ROS scavenger, TEMPOL, partially restored CCG in ZOF (CZ/NZ 0.69 ± 0.05). Treatment with mt‐targeted TEMPOL and another mt‐targeted ROS scavenger (Mito‐Quinone) restored RI‐induced CCG in ZOF to a similar extent (CZ/NZ 0.64 ± 0.01 and 0.75 ± 0.04, respectively). Treatment with the NAD(P)H oxidase inhibitor, apocynin also partially rescued CCG in ZOF and in a rat model of the metabolic syndrome (JCR), where OxStress is similarly elevated and CCG compromised (CZ/NZ 0.50 ± 0.02 and 0.65 ± 0.03, respectively). We conclude that both NAD(P)H oxidase‐ and mt‐derived OxStress are important in the regulation of CCG, and lowering of both may be necessary for restoration of CCG in the prediabetic metabolic syndrome. Support: AHA 0630285N, NIH RR018766, NIH 32788.