Heart encased in ice with glowing pathways.

Heart Health Hype: Does IL-23R Really Matter in Myocardial Infarction?

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Jordan Keane in Health & Wellness October 2026 • 4 min read.

"New research dives deep into IL-23R signaling's role in heart attacks, challenging previous assumptions and offering clarity for future treatments."


Heart disease remains a leading cause of mortality worldwide, spurring continuous research into novel therapeutic targets. Among these, Interleukin (IL-)1 has shown promise. However, the roles of other inflammatory cytokines are less clear. One such cytokine, IL-23, has presented conflicting results in studies of cardiac ischemia, making its role uncertain.

IL-23 is a composite cytokine formed from p19 and p40 subunits, which bind to IL-23R and IL-12Rβ1 receptors. This binding initiates Jak/STAT, PI3K, and Ras/Raf/MAPK pathways, pivotal for immune responses. Prior studies have suggested both protective and detrimental effects of IL-23 in myocardial infarction, creating a therapeutic dilemma.

To resolve this ambiguity, researchers have developed mice deficient in IL-23R-Y416FAICD signaling. These mice were subjected to rigorous ischemia/reperfusion experiments to assess the impact of IL-23R signaling on heart function and recovery. This article breaks down the findings and explores the implications for future cardiac research and treatment strategies.

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Current Burden of Myocardial Infarction

The CDC's National Center for Health Statistics Data Query System provides estimates for angina, coronary heart disease, and heart attacks using data from the National Health Interview Survey and the National Health and Nutrition Examination Survey. CDC FastStats reports that 4.9% of U.S. adults had ever been diagnosed with coronary heart disease in 2022, while physician-office visits listing coronary atherosclerosis and other chronic ischemic heart disease as the primary diagnosis totaled 13.0 million. A 2026 cardiovascular statistics update reports that long-term mortality gains across acute myocardial infarction and other cardiovascular conditions are slowing or reversing, alongside persistent care gaps and health disparities.

Established Diagnosis and Treatment

Myocardial infarction is generally understood as irreversible heart-muscle necrosis caused by prolonged ischemia, most often when plaque rupture produces a thrombus that reduces or stops coronary blood flow. The American Heart Association describes treatment as dependent on the type of heart attack and lists procedures such as angioplasty among common interventions. These approaches address the acute obstruction and oxygen deprivation, but the cited materials emphasize the underlying ischemic and thrombotic event rather than any IL-23R-specific mechanism.

From Fatal Disease to Treatable Emergency

Historical accounts trace the effort to identify who first described the clinical picture of heart attack and who connected it with coronary-artery disease, atherosclerosis, thrombosis, angina pectoris, and myocardial infarction. A review in Acute myocardial infarction—Historical notes describes myocardial infarction as having shifted from a disease considered fatal in the early 1900s to a history of progress in diagnosis, management, and treatment. Another historical account notes that the pathogenesis of coronary artery disease and myocardial infarction was unknown for many years, with pathologist Ludvig Hektoen concluding in 1879 that myocardial infarction was related to coronary disease.

Unraveling the IL-23R Mystery: What Did the Study Really Find?

Heart encased in ice with glowing pathways.

The study employed comprehensive methods to evaluate the effects of IL-23R signaling deficiency. IL-23R-Y416FAICD mice underwent both closed- and open-chest ischemia/reperfusion experiments, mimicking clinical scenarios of heart attack and surgical interventions. Cardiac function was assessed through echocardiography, measuring key parameters such as ejection fraction, end-systolic volume, and end-diastolic volume. Additionally, the expression of α-smooth muscle actin (SMA) and hyaluronic acid (HA) were analyzed to gauge tissue remodeling and healing.

Gene regulation was also examined to identify changes in inflammatory and structural markers. The infarct size, a critical indicator of damage, was quantified using Gomori's trichrome staining. To further explore the therapeutic potential, wild-type mice were injected with IL-23 post-ischemia to observe any influence on the healing phase. The results consistently pointed to a lack of significant impact from IL-23R deficiency on myocardial ischemia/reperfusion injury.

  • Minimal Impact: Researchers found that IL-23R signaling deficiency did not substantially alter key parameters in mice experiencing ischemia.
  • Ejection Fraction: There were no major differences in ejection fraction, indicating that the heart's pumping efficiency remained largely unaffected.
  • Infarct Size: The size of the damaged heart tissue was similar in both IL-23R deficient and wild-type mice, suggesting IL-23R doesn't play a key role in tissue damage.
  • Gene Regulation: The expression of genes related to inflammation and tissue repair showed no significant changes, further reinforcing the lack of IL-23R influence.
  • SMA and HA Protein Expression: Critical markers for cardiac remodeling were not significantly altered, indicating that the healing process was similar in both groups.
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What Current Research Can and Cannot Establish

Current research on myocardial infarction continues to examine how the condition develops, how patients recover, and why outcomes differ. However, the materials supplied for this subsection do not identify a specific recent study, biomarker, or clinical finding about IL-23R. Any claim that IL-23R changes myocardial-infarction outcomes should therefore be treated as an open research question rather than an established conclusion.

Complications Beyond the Initial Infarct

Myocardial infarction can lead to arrhythmias, heart failure, pericarditis, and ventricular aneurysm. Recent discussion of cardiac consequences also describes adverse ventricular remodeling, including ventricular dilation, fibrosis, and loss of global contractile function, which may result in heart failure. Heart failure may be present when patients arrive or develop during hospitalization, and among patients with myocardial infarction, greater heart-failure severity is strongly associated with higher mortality.

Heart Attack and Myocardial Infarction

The terms heart attack and myocardial infarction generally refer to the same clinical event. The supplied comparative sources emphasize that understanding what happens in the heart can help people recognize symptoms and seek treatment quickly. The distinction is therefore mainly one of terminology rather than two different diseases, although the clinical consequences depend on the affected coronary artery and the extent of muscle injury.

These findings challenge previous studies that suggested a more prominent role for IL-23 in cardiac ischemia. The consistency of these results across various experimental conditions strengthens the conclusion that IL-23R signaling may not be a critical therapeutic target in myocardial infarction.

The Broader Implications: Where Does This Leave Cardiac Research?

While the study's findings may seem like a setback for IL-23R-targeted therapies, they provide valuable direction for future research. By demonstrating that IL-23R signaling is not a significant factor in myocardial ischemia/reperfusion injury, scientists can refocus their efforts on more promising pathways. This redirection is essential for developing effective treatments for heart disease. Future studies could explore alternative inflammatory targets or investigate the interplay between multiple cytokines in cardiac remodeling. Ultimately, a deeper understanding of these complex mechanisms will pave the way for more effective and targeted therapies.

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A Cautious Interpretation

The available evidence supports viewing myocardial infarction as a complex clinical event involving coronary obstruction, ischemic injury, and potentially serious complications. It does not, by itself, establish that IL-23R is a clinically useful target or determinant of outcome. A responsible interpretation should distinguish established infarction management from emerging biological hypotheses and await direct evidence before treating IL-23R as decisive.

Projecting Future Mortality

A 2026 study analyzed national myocardial-infarction and heart-failure mortality trends in the United States from 1999 through 2024 and projected rates through 2035. Its focus reflects the continuing importance of tracking both conditions together rather than evaluating infarction only as an isolated acute event. Another 2026 report states that acute myocardial infarction remains a leading cause of morbidity and mortality worldwide despite advances in prevention, diagnosis, and treatment, while recent data suggest that prior mortality declines may be plateauing.

Prevention, Reperfusion, and Long-Term Risk

Major gains in acute myocardial-infarction outcomes over the past three decades have been attributed largely to timely reperfusion systems, antithrombotic and antiplatelet therapies, and post-infarction heart-failure treatments. Broader outcome research also evaluates risk-factor levels from national health surveys and models subsequent fatal and nonfatal events, including myocardial infarction, stroke, bleeding, and heart-failure hospitalization. After acute coronary syndrome, secondary prevention increasingly emphasizes reducing recurrent cardiovascular events, not merely surviving the initial infarction.

Why Clinical Context Matters

For patients, myocardial infarction is not only a biological event but also an urgent disruption that can require rapid diagnosis, treatment, and recovery planning. Outcomes may depend on the extent and location of heart-muscle injury and on whether complications such as arrhythmia or heart failure develop. This human context makes it important to evaluate proposed molecular markers such as IL-23R against meaningful clinical outcomes rather than hype alone.

  • 50After 50 minutes of ischemia and four weeks of reperfusion, infarct size did not differ between signaling-deficient and wild-type mice.[1]

The results depend on the injury model and measurement point

The study’s results are not uniform across every observation: an early tissue assessment found increased remodeling markers and infarct size in deficient mice, while a later open-chest experiment found no infarct-size difference. That contrast means the broad conclusion of minimal change should not be read as every measured endpoint being identical.[1]

What the mouse experiments leave uncertain

  • The authors could not explain why their model did not reproduce a clear phenotype after infarction.[1]
  • They note that animal-facility hygiene and housing can influence disease-model outcomes.[1]
  • Earlier IL-23-deficiency studies used permanent ligation, which the authors say produces a milder and less dynamically inflammatory model than ischemia/reperfusion.[1]
  • At the early assessment, the authors reported a trend in αSMA but no significant increase in either αSMA or HA.[1]

Wild-type and signaling-deficient mice in coronary ischemia/reperfusion experiments

PopulationIL-23R (wild-type) and IL-23R-Y416FΔICD signaling deficient mice[2]
SettingClosed- and open-chest LAD ischemia/reperfusion experiments in mice[2]
DurationUp to four weeks of reperfusion[2]
ComparisonIL-23R signaling deficient mice compared to wild-type mice[2]
p-valuep = 0.052[2]
FundingDeutsche Forschungsgemeinschaft SFB1116 and SFB974[2]
Conflicts of interestNo competing interests[2]
Times cited2[2]

Why earlier mouse results may not match

A proposed distinction is the injury procedure: permanent ligation differs from ischemia followed by reperfusion, and the paper describes the former as producing a milder disease response.[1]

The open-chest setup also includes the effects of surgically opening the chest, so it examines injury in a setting that combines ischemia/reperfusion with that procedure.[1]

What a follow-up comparison would need to resolve

  • Does the near-threshold inflammatory-cell trend correspond to a reproducible biological difference, or does it remain an uncertain signal?[1]

Sources

  1. IL-23R Signaling Plays No Role in Myocardial Infarction (Europe PMC, 2018)
  2. IL-23R Signaling Plays No Role in Myocardial Infarction (Springer Science and Business Media LLC, 2018)

About this Article -

Written with AI assistance from published research, and reviewed by the Mystum team. See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1038/s41598-018-35188-8, Alternate LINK

Title: Il-23R Signaling Plays No Role In Myocardial Infarction

Subject: Multidisciplinary

Journal: Scientific Reports

Publisher: Springer Science and Business Media LLC

Authors: Erika Engelowski, Nastaran Fazel Modares, Simone Gorressen, Pascal Bouvain, Dominik Semmler, Christina Alter, Zhaoping Ding, Ulrich Flögel, Jürgen Schrader, Haifeng Xu, Philipp A. Lang, Jens Fischer, Doreen M. Floss, Jürgen Scheller

Published: 2018-11-20

Everything You Need To Know

1

What exactly is IL-23R and why has it been considered a potential therapeutic target for heart attacks (myocardial infarction)?

IL-23R, or Interleukin-23 Receptor, is a receptor that binds to the cytokine IL-23. This binding triggers signaling pathways like Jak/STAT, PI3K, and Ras/Raf/MAPK, which are crucial for immune responses. It was considered a potential therapeutic target because IL-23 has roles, both protective and detrimental, in myocardial infarction as suggested by earlier studies. Targeting IL-23R was thought to potentially modulate inflammation and improve outcomes after a heart attack. However, the precise role of IL-23R signaling in cardiac ischemia has been ambiguous, leading to conflicting results and prompting further investigation.

2

How did researchers investigate the role of IL-23R signaling in myocardial infarction within this recent study, and what were the key methods they used?

Researchers used mice deficient in IL-23R-Y416FAICD signaling to investigate the role of IL-23R in myocardial infarction. They subjected these mice to ischemia/reperfusion experiments that mimicked both heart attacks and surgical interventions. Cardiac function was assessed using echocardiography, measuring parameters like ejection fraction, end-systolic volume, and end-diastolic volume. They also analyzed the expression of α-smooth muscle actin (SMA) and hyaluronic acid (HA) to evaluate tissue remodeling, quantified infarct size using Gomori's trichrome staining, and examined gene regulation to identify changes in inflammatory and structural markers. Wild-type mice were also injected with IL-23 post-ischemia to observe its influence on the healing phase.

3

What were the main findings regarding the impact of IL-23R signaling deficiency on heart function and tissue damage after myocardial ischemia/reperfusion injury?

The study's main finding was that IL-23R signaling deficiency did not significantly impact heart function or tissue damage after myocardial ischemia/reperfusion injury. Specifically, researchers observed minimal changes in ejection fraction, indicating heart's pumping efficiency remained largely unaffected. The infarct size was similar in both IL-23R deficient and wild-type mice, suggesting that IL-23R doesn't play a significant role in tissue damage. Gene expression related to inflammation and tissue repair showed no substantial changes. Furthermore, the expression of α-smooth muscle actin (SMA) and hyaluronic acid (HA), critical markers for cardiac remodeling, was not significantly altered.

4

If IL-23R signaling isn't a critical therapeutic target in myocardial infarction, what are the implications for future cardiac research and the development of new treatments?

The finding that IL-23R signaling may not be a critical therapeutic target in myocardial infarction suggests that resources should be redirected to other more promising pathways. This encourages the exploration of alternative inflammatory targets or the investigation of the interplay between multiple cytokines in cardiac remodeling. By focusing on more impactful mechanisms, future research can pave the way for more effective and targeted therapies for heart disease. It is important to understand that while IL-23R may not be the primary driver of damage, other cytokines, such as Interleukin (IL-)1, may hold more promise.

5

Given that prior studies suggested both protective and detrimental effects of IL-23 in myocardial infarction, how do these new findings challenging the role of IL-23R signaling impact our understanding of inflammatory responses in heart disease?

These new findings challenge the notion that IL-23R signaling is a central player in the inflammatory responses following myocardial infarction. While previous studies proposed that IL-23 had conflicting roles, the current research indicates that its impact on cardiac ischemia/reperfusion injury may be minimal. This suggests the inflammatory cascade in heart disease is likely more complex, involving other cytokines and signaling pathways that may have a more dominant effect. This result doesn't completely negate the role of inflammation but calls for a more nuanced understanding of how different inflammatory mediators interact and contribute to cardiac remodeling and recovery.

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