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Updated: Jun 10, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Protease-activated receptor 2 deficiency reduces cardiac ischemia/reperfusion injury
Silvio Antoniak1, Mauricio Rojas, Denise Spring
1Division of Hematology/Oncology, Department of Medicine, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7035, USA.
Objective:
To investigate the effect of protease-activated receptor (PAR) 2 deficiency on ischemia/reperfusion (I/R) injury-induced infarct size, inflammation, heart remodeling, and cardiac function.
Methods And Results:
PAR-2 signaling enhances inflammation in different diseases. The effect of PAR-2 deficiency in cardiac I/R injury is unknown. PAR-2(-/-) mice and wild-type littermates were subjected to 30 minutes of ischemia and up to 4 weeks of reperfusion. Infarct size, oxidative/nitrative stress, phosphorylation of mitogen-activated protein kinases, and inflammatory gene expression were assessed 2 hours after reperfusion. Changes in heart size and function were measured by echocardiography up to 4 weeks after reperfusion. Infarct size was significantly reduced in hearts of PAR-2(-/-) mice compared with wild-type littermates. In addition, oxidative/nitrative stress, phosphorylation of mitogen-activated protein kinase, and expression of proinflammatory genes were significantly attenuated in injured hearts of PAR-2(-/-) mice. Finally, PAR-2(-/-) mice were protected from postinfarction remodeling and showed less impairment in heart function compared with wild-type littermates up to 4 weeks after I/R injury.
Conclusions:
PAR-2 deficiency reduces myocardial infarction and heart remodeling after I/R injury.
Insights
Protease-activated receptor (PAR) 2 deficiency significantly reduces heart damage and inflammation following ischemia/reperfusion injury. PAR-2 knockout mice showed improved cardiac function and less remodeling, highlighting PAR-2
Area of Science:
- Cardiovascular Research
- Inflammation Biology
- Molecular Medicine
Background:
- Protease-activated receptor (PAR) 2 signaling is implicated in inflammatory processes across various diseases.
- The specific role of PAR-2 in myocardial ischemia/reperfusion (I/R) injury remains largely uncharacterized.
- Understanding PAR-2's contribution to cardiac injury is crucial for developing targeted therapeutic strategies.
Purpose of the Study:
- To elucidate the impact of protease-activated receptor (PAR) 2 deficiency on myocardial infarct size, inflammation, and cardiac remodeling post-I/R injury.
- To assess the functional consequences of PAR-2 absence in a mouse model of cardiac I/R.
- To investigate the underlying mechanisms, including oxidative stress and inflammatory gene expression, modulated by PAR-2.
Main Methods:
- Utilized a murine model of cardiac I/R injury, comparing PAR-2 knockout (PAR-2(-/-)) mice with wild-type littermates.
- Induction of 30 minutes of ischemia followed by up to 4 weeks of reperfusion.
- Quantification of infarct size, oxidative/nitrative stress markers, and inflammatory gene expression at 2 hours post-reperfusion.
- Echocardiography was employed to evaluate cardiac size and function up to 4 weeks post-injury.
Main Results:
- PAR-2 deficiency led to a significant reduction in myocardial infarct size compared to wild-type controls.
- Oxidative/nitrative stress, mitogen-activated protein kinase phosphorylation, and pro-inflammatory gene expression were markedly attenuated in PAR-2(-/-) mice.
- PAR-2 knockout mice exhibited protection against post-infarction cardiac remodeling and preserved cardiac function up to 4 weeks after I/R.
Conclusions:
- Genetic deficiency of PAR-2 confers significant protection against myocardial infarction and subsequent cardiac remodeling.
- PAR-2 signaling exacerbates I/R-induced cardiac injury, making it a potential therapeutic target.
- Targeting PAR-2 may represent a novel strategy to mitigate heart damage and improve outcomes after ischemic events.
