| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,1
* Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Boston, Massachusetts 02115;
Harvard Medical School, Boston, Massachusetts 02115; and
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, 807
Abstract
Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of the properties of inducible HO (HO-1) and its products, we hypothesized that HO-1 would play an important role in the regulation of cardiovascular function. In this article, we will review the role of HO-1 in the regulation of blood pressure and cardiac function and highlight previous studies from our laboratory using gene deletion and gene overexpression transgenic approaches in mice. These studies will include the investigation of HO-1 in the setting of hypertension (renovascular), hypotension (endotoxemia), and ischemia/reperfusion injury (heart). In a chronic renovascular hypertension model, hypertension, cardiac hypertrophy, acute renal failure, and acute mortality induced by one kidney–one clip surgery were more severe in HO-1-null mice. In addition, HO-1-null mice with endotoxemia had earlier resolution of hypotension, yet the mortality and the incidence of end-organ damage were higher in the absence of HO-1. In contrast, mice with cardiac-specific overexpression of HO-1 had an improvement in cardiac function, smaller myocardial infarctions, and reduced inflammatory and oxidative damage after coronary artery ligation and reperfusion. Taken together, these studies suggest that an absence of HO-1 has detrimental consequences, whereas overexpression of HO-1 plays a protective role in hypoperfusion and ischemia/reperfusion injury.
Key Words: blood pressure • cardiovascular • oxidative stress
This article has been cited by other articles:
|
|
 |
|
  G. Alba, R. El Bekay, P. Chacon, M. E. Reyes, E. Ramos, J. Olivan, J. Jimenez, J. M. Lopez, J. Martin-Nieto, E. Pintado, et al. Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils J. Leukoc. Biol., August 1, 2008; 84(2): 397 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Chon, M. C. Verhaar, H. A. Koomans, J. A. Joles, and B. Braam Role of Circulating Karyocytes in the Initiation and Progression of Atherosclerosis Hypertension, May 1, 2006; 47(5): 803 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Maines New Insights into Biliverdin Reductase Functions: Linking Heme Metabolism to Cell Signaling Physiology, December 1, 2005; 20(6): 382 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Rushworth, X.-L. Chen, N. Mackman, R. M. Ogborne, and M. A. O'Connell Lipopolysaccharide-Induced Heme Oxygenase-1 Expression in Human Monocytic Cells Is Mediated via Nrf2 and Protein Kinase C J. Immunol., October 1, 2005; 175(7): 4408 - 4415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wesseling, D. A. Ishola Jr., J. A. Joles, H. A. Bluyssen, H. A. Koomans, and B. Braam Resistance to oxidative stress by chronic infusion of angiotensin II in mouse kidney is not mediated by the AT2 receptor Am J Physiol Renal Physiol, June 1, 2005; 288(6): F1191 - F1200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Miralem, Z. Hu, M. D. Torno, K. M. Lelli, and M. D. Maines Small Interference RNA-mediated Gene Silencing of Human Biliverdin Reductase, but Not That of Heme Oxygenase-1, Attenuates Arsenite-mediated Induction of the Oxygenase and Increases Apoptosis in 293A Kidney Cells J. Biol. Chem., April 29, 2005; 280(17): 17084 - 17092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Saito, N. Ishizaka, T. Aizawa, M. Sata, N. Iso-o, E. Noiri, I. Mori, M. Ohno, and R. Nagai Iron chelation and a free radical scavenger suppress angiotensin II-induced upregulation of TGF-{beta}1 in the heart Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1836 - H1843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kravets, Z. Hu, T. Miralem, M. D. Torno, and M. D. Maines Biliverdin Reductase, a Novel Regulator for Induction of Activating Transcription Factor-2 and Heme Oxygenase-1 J. Biol. Chem., May 7, 2004; 279(19): 19916 - 19923. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
