Hypercholesterolemia Enhances 15-Lipoxygenase‚ÄìMediated Vasorelaxation and Acetylcholine-Induced Hypotension
Authors: Nitin T Aggarwal
Sandra L Pfister
William B Campbell
Journal: Arteriosclerosis Thrombosis and Vascular Biology (2008)
Discipline: CLINICAL MEDICINE
Keywords: Arachidonic acid; 15-lipoxygenase-1; THETA; HEETA; arteries
Affiliations: Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA., From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.

Abstract:  Objective: Arachidonic acid (AA) metabolites from 15-lipoxygenase-1 (15-LO-1), trihydroxyeicosatrienoic acid (THETA), and hydroxyepoxyeicosatrienoic acid (HEETA) relax arteries. We studied 15-LO-1 expression, THETA and HEETA synthesis, and their effect on arterial relaxations and blood pressure in hypercholesterolemic nonatherosclerotic rabbits. Methods and results: Immunoblots, RTPCR analysis, and (14)C-AA metabolism revealed that hypercholesterolemia increased 15-LO-1 expression in the endothelium and THETA and HEETA synthesis in the arteries. Isometric tension recording, in presence of nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibitors, showed greater relaxations to acetylcholine (ACH) and AA (max 76.0+/-4.6% and 79.5+/-2.4%, respectively) in aortas from hypercholesterolemic rabbits compared with normal rabbits (max 39.1+/-2.8% and 39.9+/-2.2%, respectively). AA induced greater hyperpolarization in the smooth muscle cells of hypercholesterolemic aortas (-45.85+/-3.0 mV) compared with normal aortas (-31.45+/-1.9 mV). The ACH- and AA-relaxations were inhibited by 15-LO-1 inhibitors. ACH induced hypotensive responses were greater in hypercholesterolemic rabbits in absence (-54.9+/-3.3%) or presence (-48.5+/-3.2%) of NOS and COX-inhibitors compared with control rabbits (-31.6+/-3.3% and -24.3+/-1.6%, respectively). BW755C reduced these responses in hypercholesterolemic rabbits to -29.3+/-2.3%. Conclusions: Hypercholesterolemia increases endothelial 15-LO-1 expression, THETA and HEETA synthesis and enhances vasorelaxation. 

Retracted: Yes

PubPeer comments:
 Most of the studies coded as individual incentives and performance quality do not meet the inclusion criteria and many of them do not measure performance quality, but performance quantity. One of the inclusion criteria is (7) the study uses adult populations (rather than children) But Cialdini, Eisenberg, Rhoads, Bator (1998) used boys and girls in the third, fourth, and fifth grades, Hamner Foster (1975) used undergraduate students and measured performance quantity (number of items scored correctly) Hatcher Ross (1991) is not at the individual level . Johnson, Dickinson, Huitema (2008) used college students and performance quantity (percentage of correctly completed checks) Mason Watts (2010) found that increased financial incentives increased the quantity, but not the quality of performance, which is not what was reported in Gerbers Konradt (2014). Menguc Barker (2003) does not investigate individual performance. The study is not at the individual level (but at the sales unit level), the design is not quasi-experimental, nor is it controlled for previous performance, and the IV (the percentage of total incentives paid to salespeople) and the DV (customer satisfaction) is self-reported by sales managers with a cross-sectional design. This is not in line with the inclusion criteria. ,