Faculty Collaboration Database

Effect of human 15-lipoxygenase-1 metabolites on vascular function in mouse mesenteric arteries and hearts. Prostaglandins Other Lipid Mediat 2013 Oct;106:8-15

Date

07/23/2013

Pubmed ID

23872364

Pubmed Central ID

PMC3844054

DOI

10.1016/j.prostaglandins.2013.07.002

Scopus ID

2-s2.0-84883361018 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Lipoxygenases regulate vascular function by metabolizing arachidonic acid (AA) to dilator eicosanoids. Previously, we showed that endothelium-targeted adenoviral vector-mediated gene transfer of the human 15-lipoxygenase-1 (h15-LO-1) enhances arterial relaxation through the production of vasodilatory hydroxyepoxyeicosatrienoic acid (HEETA) and trihydroxyeicosatrienoic acid (THETA) metabolites. To further define this function, a transgenic (Tg) mouse line that overexpresses h15-LO-1 was studied. Western blot, immunohistochemistry and RT-PCR results confirmed expression of 15-LO-1 transgene in tissues, especially high quantity in coronary arterial wall, of Tg mice. Reverse-phase HPLC analysis of [(14)C]-AA metabolites in heart tissues revealed enhanced 15-HETE synthesis in Tg vs. WT mice. Among the 15-LO-1 metabolites, 15-HETE, erythro-13-H-14,15-EETA, and 11(R),12(S),15(S)-THETA relaxed the mouse mesenteric arteries to the greatest extent. The presence of h15-LO-1 increased acetylcholine- and AA-mediated relaxation in mesenteric arteries of Tg mice compared to WT mice. 15-LO-1 was most abundant in the heart; therefore, we used the Langendorff heart model to test the hypothesis that elevated 15-LO-1 levels would increase coronary flow following a short ischemia episode. Both peak flow and excess flow of reperfused hearts were significantly elevated in hearts from Tg compared to WT mice being 2.03 and 3.22 times greater, respectively. These results indicate that h15-LO-1-derived metabolites are highly vasoactive and may play a critical role in regulating coronary blood flow.

Author List

Kriska T, Cepura C, Siangjong L, Wan TC, Auchampach JA, Shaish A, Haratz D, Kumar G, Falck JR, Gauthier KM, Campbell WB

Authors

John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Tamas Kriska PhD Research Scientist I in the Pharmacology and Toxicology department at Medical College of Wisconsin
Tina C. Wan PhD Research Scientist II in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Arachidonate 15-Lipoxygenase
Arachidonic Acid
Blood Pressure
Coronary Circulation
Coronary Vessels
Gene Expression Regulation, Enzymologic
Humans
Hyperemia
Male
Mesenteric Arteries
Mice
Mice, Transgenic
Organ Specificity
Protein Transport
Vasodilation