Background
High-mobility group box 1 (HMGB1) is a mediator of inflammation with dose-dependent
effects. In the setting of regional myocardial infarction, a high-dose HMGB1 treatment
decreases myocardial function, whereas low-dose HMGB1 improves function; however,
it is unknown what role HMGB1 has in the setting of global ischemia/reperfusion (I/R)
injury. We hypothesized that a low-dose HMGB1 treatment would improve myocardial functional
recovery and decrease infarct size after global I/R injury in association with increased
levels of cardioprotective paracrine factors and decreased inflammation.
Methods
Adult rat hearts were isolated and perfused using the Langendorff method and were
subjected to global I/R and treatment with either the vehicle, 200-ng HMGB1, or 1-μg
HMGB1. The treatment was administered during 1 min at the start of reperfusion, and
myocardial function was measured for 60 min of reperfusion. At the end of reperfusion,
the hearts were sectioned and incubated in triphenyltetrazolium chloride to assess
myocardial infarct size or homogenized to measure levels of inflammatory cytokines
and growth factors.
Results
Postischemic treatment with 200-ng HMGB1 significantly improved myocardial functional
recovery after global I/R in association with decreased infarct size and decreased
interleukin-1 (IL-1), IL-6, IL-10, and vascular endothelial growth factor (VEGF) levels.
In addition, 1-μg HMGB1 decreased myocardial inflammation but did not result in subsequent
improvement in functional recovery.
Conclusion
In the setting of global I/R, 200-ng postischemic HMGB1 treatment improves myocardial
function and decreases infarct size in association with suppressed myocardial inflammation.
These results suggest a potential role for exogenous HMGB1therapy in the acute postischemic
period.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications.Circulation. 1990; 81: 1161-1172
- The inflammatory response in myocardial infarction.Cardiovasc Res. 2002; 53: 31-47
- The first minutes of reperfusion: a window of opportunity for cardioprotection.Cardiovasc Res. 2004; 61: 365-371
- Myocardial reperfusion: a double-edged sword?.J Clin Invest. 1985; 76: 1713-1719
- Potential novel pharmacological therapies for myocardial remodelling.Cardiovasc Res. 2009; 81: 519-527
- Myocardial reperfusion injury.N Engl J Med. 2007; 357: 1121-1135
- HMG-1 rediscovered as a cytokine.Shock. 2001; 15: 247-253
- Release of chromatin protein HMGB1 by necrotic cells triggers inflammation.Nature. 2002; 418: 191-195
- Mini-review: the nuclear protein HMGB1 as a proinflammatory mediator.Eur J Immunol. 2004; 34: 1503-1512
- RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent macrophages.Scand J Immunol. 2005; 61: 1-9
- HMG-1 as a late mediator of endotoxin lethality in mice.Science. 1999; 285: 248-251
- High-mobility group box-1 in ischemia-reperfusion injury of the heart.Circulation. 2008; 117: 3216-3226
- High-mobility group box 1 restores cardiac function after myocardial infarction in transgenic mice.Cardiovasc Res. 2008; 80: 40-46
- Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac C-kit+ cell proliferation and differentiation.Circ Res. 2005; 97: e73-e83
- Vascular endothelial growth factor improves myocardial functional recovery following ischemia/reperfusion injury.J Surg Res. 2008; 150: 286-292
- Interleukin-10 from transplanted bone marrow mononuclear cells contributes to cardiac protection after myocardial infarction.Circ Res. 2008; 103: 203-211
- Embryonic stem cells attenuate myocardial dysfunction and inflammation after surgical global ischemia via paracrine actions.Am J Physiol Heart Circ Physiol. 2008; 295: H1726-H1735
- One hour reperfusion is enough to assess function and infarct size with TTC staining in Langendorff rat model.Cardiovasc Drugs Ther. 2009; 23: 327-331
- Effects of HMGB1 on ischemia-reperfusion injury in the rat heart.Circ J. 2008; 72: 1178-1184
- Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling.Cardiovasc Res. 2009; 81: 565-573
- Severity of sepsis is correlated with the elevation of serum high-mobility group box 1 in rats.Chin Med J (Engl). 2009; 122: 449-454
- Biology of TNFalpha and IL-10, and their imbalance in heart failure.Heart Fail Rev. 2009; 14: 113-123
- IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury.J Immunol. 2000; 165: 2798-2808
- Tumor necrosis factor in the heart.Am J Physiol. 1998; 274: R577-R595
- Human myocardial tissue TNFalpha expression following acute global ischemia in vivo.J Mol Cell Cardiol. 1998; 30: 1683-1689
- Mechanism of TNFalpha-induced IL-1alpha, IL-1beta and IL-6 expression in human cardiac fibroblasts: effects of statins and thiazolidinediones.Cardiovasc Res. 2007; 76: 81-90
- HMGB1-stimulated human primary cardiac fibroblasts exert a paracrine action on human and murine cardiac stem cells.J Mol Cell Cardiol. 2008; 44: 683-693
- Preconditioning with high mobility group box 1 protein protects against myocardial ischemia-reperfusion injury.Int J Cardiol. 2009; (e-pub Jun 17)
- Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice.Int J Obes Relat Metab Disord. 2000; 24: 639-646
- Modulated inflammation by injection of high-mobility group box 1 recovers post-infarction chronically failing heart.Circulation. 2008; 118: S106-S114
- High-mobility group box 1 protein (HMGB1) in ischaemic heart disease: beneficial or deleterious?.Cardiovasc Res. 2008; 80: 5-6
- The cytokine activity of HMGB1.J Leukoc Biol. 2005; 78: 1-8
- The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system.J Biol Chem. 1995; 270: 25752-25761
- High mobility group box 1 protein interacts with multiple Toll-like receptors.Am J Physiol Cell Physiol. 2006; 290: C917-C924
- Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1).Angiogenesis. 2008; 11: 91-99
- HMGB1 loves company.J Leukoc Biol. 2009; 86: 573-576
Article info
Publication history
Published online: August 20, 2010
Accepted:
July 1,
2010
Footnotes
Supported by grants R01GM070628 (to D.R.M.), R01HL085595 (to D.R.M.), 1F32HL092718 (to A.M.A.), 1F32HL092719 (to J.L.H.), and 1F32HL093987 (to B.R.W.) from the National Institutes of Health.
Identification
Copyright
© 2011 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
