Abstract
Introduction
Whilst blood flow restoration is critical following myocardial infarction (MI), ischemia-reperfusion injury (IRI) accounts for ~50% of the final infarct size. Elderly patients have a poorer prognosis which may be linked to increased coronary microvessels susceptibility to injury. The newly discovered and inflammatory cytokine, interleukin-36 (IL-36), could potentially mediate these disturbances. However, its role in myocardial IRI is not known.
Methods
Myocardial IRI was induced in adult (3-months) and aged (>18-months) mice. In some studies, recombinant mouse IL-36Ra (15μg/mouse) was injected intra-arterially. IL-36R/α/β, and VCAM-1 expression were investigated immunohistochemically or using western blots. Beating heart coronary microcirculation was imaged intravitally in vivo and also ex vivo using multiphoton microscopy. Topical cytokine application was also observed intravitally. Laser speckle contrast imaging was used to determine perfusion, and infarct size was measured using dual TTC/Evans Blue staining.
Results
IL-36R/α/β were expressed predominantly on the microvasculature of murine hearts, with some cardiomyocyte expression also observed. Expression of IL-36R/α/β and VCAM-1 significantly increased with injury and age (see Table 1). Topical application of all IL-36 cytokines induced a significant (p
Conclusion
These novel results are the first to demonstrate myocardial presence of IL-36 and its receptor. Our novel findings of enhanced coronary microcirculatory perturbations associated with age may explain the poorer outcomes in elderly MI patients. Importantly, we are the first to demonstrate that targeting IL-36 was vasculoprotective and may be a potential novel therapy for treatment of myocardial IRI.
Whilst blood flow restoration is critical following myocardial infarction (MI), ischemia-reperfusion injury (IRI) accounts for ~50% of the final infarct size. Elderly patients have a poorer prognosis which may be linked to increased coronary microvessels susceptibility to injury. The newly discovered and inflammatory cytokine, interleukin-36 (IL-36), could potentially mediate these disturbances. However, its role in myocardial IRI is not known.
Methods
Myocardial IRI was induced in adult (3-months) and aged (>18-months) mice. In some studies, recombinant mouse IL-36Ra (15μg/mouse) was injected intra-arterially. IL-36R/α/β, and VCAM-1 expression were investigated immunohistochemically or using western blots. Beating heart coronary microcirculation was imaged intravitally in vivo and also ex vivo using multiphoton microscopy. Topical cytokine application was also observed intravitally. Laser speckle contrast imaging was used to determine perfusion, and infarct size was measured using dual TTC/Evans Blue staining.
Results
IL-36R/α/β were expressed predominantly on the microvasculature of murine hearts, with some cardiomyocyte expression also observed. Expression of IL-36R/α/β and VCAM-1 significantly increased with injury and age (see Table 1). Topical application of all IL-36 cytokines induced a significant (p
Conclusion
These novel results are the first to demonstrate myocardial presence of IL-36 and its receptor. Our novel findings of enhanced coronary microcirculatory perturbations associated with age may explain the poorer outcomes in elderly MI patients. Importantly, we are the first to demonstrate that targeting IL-36 was vasculoprotective and may be a potential novel therapy for treatment of myocardial IRI.
| Original language | English |
|---|---|
| Pages (from-to) | 7 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 173 |
| Issue number | supplement |
| DOIs | |
| Publication status | Published - 31 Dec 2022 |
| Event | XXIV World Congress of the International Society for Heart Research - Mercure Hotel MOA, Berlin, Germany Duration: 12 Jun 2022 → 16 Jun 2022 https://www.ishr2022berlin.de/ |