Rosiglitazone Protects against Ischemia/Reperfusion-Induced Leukocyte Adhesion in the Zucker Diabetic Fatty Rat
Abstract
Increased susceptibility to atherosclerosis increases the risk of mortality in type 2 diabetic patients. Leukocyte adhesion to the endothelium is a critical step in atherogenesis. In addition to its insulin-sensitizing effects, rosiglitazone (RSG) possesses anti-inflammatory properties. However, the effects of RSG on the initial phase of leukocyte recruitment (rolling, adhesion) have not been studied in vivo. This study tested the hypothesis that RSG treatment of Zucker diabetic fatty (ZDF) rats inhibits ischemia/reperfusion-induced leukocyte adhesion to the endothelium. Male ZDF rats (16 weeks) were treated with RSG (3 mg/kg/day, p.o.) 7 days before experimentation. Leukocyte-endothelial interactions in cremaster venules were recorded using intravital microscopy prior to 30 min of ischemia and during a 90-min reperfusion period. Although blood pressure, plasma glucose, and insulin were not different between treatment groups, RSG treatment was associated with reduced leukocyte rolling and inhibition of leukocyte adhesion throughout the reperfusion period (P < 0.01). Cremaster mRNA expression of vascular cell adhesion molecule-1 (VCAM-1) was reduced by 35% in RSG-treated animals (P < 0.01), whereas P- and E-selectin and intercellular adhesion molecule-1 (ICAM-1) were unchanged. Immunostaining for P-selectin, E-selectin, and VCAM-1 was reduced by 21, 61, and 50%, respectively (for all, P < 0.05), in RSG-treated animals. Inhibition of ischemia/reperfusion-induced leukocyte adhesion might contribute to the utility of RSG as a therapy for vascular disease.
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Studies in older Zucker rats demonstrated reduced recovery from ischemia, which could be prevented by treating these animals with a TZD.
“In contrast, studies in older Zucker rats demonstrated reduced recovery from ischemia, which could be prevented by treating these animals with a TZD (159, 322, 389).”
From Cardiac remodeling in obesity (2008) · cites this paper as [159]
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- Authors
- Johns, D. G., Ao, Z., Eybye, M., Olzinski, A., Costell, M., Gruver, S., Smith, S. A., Douglas, S. A., & Macphee, C. H.
- Affiliations
- GlaxoSmithKline (United States) (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 315
- Issue
- 3
- Pages
- 1020-1027
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2148063636
- Cited by
- 22
- References
- 43
- Citations by year
- 2020: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2012: 1
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- rosiglitazone, leukocyte adhesion, leukocyte rolling, ischemia-reperfusion injury, endothelial selectins, VCAM-1, P-selectin, E-selectin, ICAM-1, atherogenesis, type 2 diabetes, anti-inflammatory activity, vascular disease, Zucker diabetic fatty rats
- MeSH terms
- Rosiglitazone, Animals, Blood Glucose, Blood Pressure, Cell Adhesion, Fatty Acids, Nonesterified, Hypoglycemic Agents, Immunohistochemistry, Insulin, Leukocytes, Male, Myocardial Infarction, Rats, Zucker, Myocardial Reperfusion Injury, Vascular Cell Adhesion Molecule-1, Thiazolidinediones, Rats, Adiponectin
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