ArticleJCI insight2018
iRhom2-mediated proinflammatory signalling regulates heart repair following myocardial infarction.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Deficiency of Inactive Rhomboid Protein 2 (iRhom2) Attenuates Macrophage Atherogenicity.Biology · 2026Article
- iRhom2 regulates HMGB1 secretion to modulate inflammation and hepatocyte senescence in an in vitro model of ischemia-reperfusion injury.Cell death & disease · 2026Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Pulmonary Hypertension and Right Ventricle: A Pathophysiological Insight.Clinical Medicine Insights. Cardiology · 2024Review
- The phagocytic role of macrophage following myocardial infarction.Heart failure reviews · 2023Review
- The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth.Life science alliance · 2023Article
- iRhom2: An Emerging Adaptor Regulating Immunity and Disease.International journal of molecular sciences · 2020Review
- Adaptive and innate immune mechanisms in cardiac fibrosis complicating pulmonary arterial hypertension.Physiological reports · 2020Review
- The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders.Frontiers in cardiovascular medicine · 2020Review
- Cardiac inflammatory CD11b/c cells exert a protective role in hypertrophied cardiomyocyte by promoting TNFRScientific reports · 2019Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The role of proinflammation, and specifically TNF-α, on downstream fibrosis and healing after cardiac injury remains unknown. Using iRhom2-deficient mice, which lack myeloid-specific shedding of TNF-α, we reveal increased macrophages (MΦs) that were skewed towards a more proinflammatory (M1) state at day 4, followed by more reparative, antiinflammatory (M2) state at day 7 after myocardial infarction (MI). However, associated functional cytokine expression was significantly reduced in iRhom2-mutant M1 and M2 MΦs, respectively. A dampened proinflammatory signature in iRhom2-deficient mice during the acute phase of injury and subsequent changes in MΦ polarization were associated with reduced phagocytosis and a more sparse distribution within the scar region. This resulted in impaired collagen deposition and fibrosis, and increased left ventricular remodelling and mortality in iRhom2-deficient mice after MI. Our findings reveal a requirement for an iRhom2-mediated proinflammatory response during downstream scarring and fibrosis, which is driven in part by TNF-α signaling. These conclusions challenge the existing model that infarct repair is determined exclusively by antiinflammatory signaling of M2 MΦs, and as such we propose an alternative view of immunomodulation to maintain effective healing after infarction.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.