Mechanism of Heme-Heme Oxygenase System Impairment of Endothelium Contraction in the Spontaneously Hypertensive Rat

Document Type


Publication Date

Fall 9-26-2011


Heme oxygenase (HO) 1 and HO-2 gene expressions are known to increase cellular antioxidant and anti-inflammatory properties through activation of a battery of cytoprotective systems, including decreases in cyclooxygenase 1 and NADPH oxidase (NOX-2) and elevated levels of extracellular superoxide dismutase and NO. The heme-HO system (HO-1 and HO-2) acts as an endogenous anti-inflammatory and protective circuit critical for a self-resolving inflammatory-reparative process. A study by Li et al,1 which appears in this issue of Hypertension, shows that upregulation of heme oxygenase (HO) 1 prevents endothelium contraction in aorta of spontaneously hypertensive rats (SHRs) via a decrease in cyclooxygenase (COX) 1, not COX-2. Induction of HO-1 was observed in cultured endothelial cells and in vivo after treatment with both heme and hemoglobin. In the present article, Li et al1 showed that, in aorta isolated from either wild-type or SHR animals, levels of HO-1 are low. HO-1 under physiological conditions is expressed at low levels and does not seem to affect the basal levels of heme-dependent enzyme activity. On the other hand, HO-2, the constitutive enzyme, is the main determinant for the regulation of the basal physiological levels of various hemeproteins, including COX, NOX2, inducible NO synthase, and CYP450. COX-1/-2 are hemeproteins that catalyze the conversion of arachidonic acid (AA) to prostaglandin H2, the precursor of prostanoids that participate in the regulation of vascular function. Heme binds to the COX apoenzyme with a stoichiometry of ≈1 heme molecule per each subunit. Accordingly, the possibility arises that variations in the cellular levels of heme impact the amount of catalytically active COX present in cells.


The version of record is available from the publisher at http://hyper.ahajournals.org/content/58/5/772.full.pdf. Copyright © 2011 American Heart Association, Inc. All rights reserved.

doi: 10.1161/HYPERTENSIONAHA.111.178525