Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice

Palazzo, Anthony J.; Jones, Steven P.; Girod, Wesley G.; Anderson, Donald C.; Granger, D. Neil; Lefer, David J.

doi:10.1152/ajpheart.1998.275.6.h2300

Cited by 93 publications

(85 citation statements)

References 31 publications

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“…This, in turn, is associated with increased expression of adhesion molecules including ICAM and VCAM (46,47), which can be blocked by proteasome inhibitors (47) or other compounds capable of inhibiting NF-κB activity (40). Furthermore, inhibition of proteasome-mediated IκBα degradation (48) or adhesion molecule expression has been shown to reduce significantly ischemia-reperfusion injury (49)(50)(51).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of ubiquitin-proteasome pathway–mediated IκBα degradation by a naturally occurring antibacterial peptide

Gao¹,

Lecker²,

Post³

et al. 2000

J. Clin. Invest.

153

124

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Section: Discussionmentioning

confidence: 99%

Inhibition of ubiquitin-proteasome pathway–mediated IκBα degradation by a naturally occurring antibacterial peptide

Gao¹,

Lecker²,

Post³

et al. 2000

J. Clin. Invest.

153

124

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“…Experiments using genetically targeted animals have contributed to our understanding of the role of integrins in experimental myocardial infarction. CD18 deficient mice demonstrated significant reduction in neutrophil accumulation following myocardial ischemia and reperfusion [203]. Furthermore, treatment with an antibody to Vascular Cell Adhesion Molecule (VCAM)-1 significantly attenuated neutrophil emigration in the infarcted myocardium of CD18-null mice, but did not diminish myocardial injury [204].…”

Section: The Neutrophilsmentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

563

499

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Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

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“…ICAM-1 is upregulated on endothelial cells of coronary vessels following ischemia, which is in large part due to the release of proinflammatory cytokines such as TNF-α (21,22). Blocking ICAM-1 has been shown to ameliorate myocardial ischemia/reperfusion injury in rodent models of heart transplantation and transient ligation of a coronary artery (23,24). The ICAM-1-mutant strain used in this study is not completely devoid of ICAM-1 expression, but rather expresses alternatively spliced isoforms that lack an Iglike domain, which is the binding site for Mac-1.…”

Section: Figurementioning

confidence: 99%

Intravital 2-photon imaging of leukocyte trafficking in beating heart

Li¹,

Nava²,

Bribriesco³

et al. 2012

J. Clin. Invest.

111

118

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Two-photon intravital microscopy has substantially broadened our understanding of tissue-and organ-specific differences in the regulation of inflammatory responses. However, little is known about the dynamic regulation of leukocyte recruitment into inflamed heart tissue, largely due to technical difficulties inherent in imaging moving tissue. Here, we report a method for imaging beating murine hearts using intravital 2-photon microscopy. Using this method, we visualized neutrophil trafficking at baseline and during inflammation. Ischemia reperfusion injury induced by transplantation or transient coronary artery ligation led to recruitment of neutrophils to the heart, their extravasation from coronary veins, and infiltration of the myocardium where they formed large clusters. Grafting hearts containing mutant ICAM-1, a ligand important for neutrophil recruitment, reduced the crawling velocities of neutrophils within vessels, and markedly inhibited their extravasation. Similar impairment was seen with the inhibition of Mac-1, a receptor for ICAM-1. Blockade of LFA-1, another ICAM-1 receptor, prevented neutrophil adherence to endothelium and extravasation in heart grafts. As inflammatory responses in the heart are of great relevance to public health, this imaging approach holds promise for studying cardiac-specific mechanisms of leukocyte recruitment and identifying novel therapeutic targets for treating heart disease.

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Myocardial ischemia-reperfusion injury in CD18- and ICAM-1-deficient mice

Cited by 93 publications

References 31 publications

Inhibition of ubiquitin-proteasome pathway–mediated IκBα degradation by a naturally occurring antibacterial peptide

Inhibition of ubiquitin-proteasome pathway–mediated IκBα degradation by a naturally occurring antibacterial peptide

The immune system and cardiac repair

Intravital 2-photon imaging of leukocyte trafficking in beating heart

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