1984Innate immune nod1/rip2 signaling is essential for cardiac hypertrophic response with a surprising critical interaction with mitochondrial danger activator
Bibliographic record
Abstract
Background: Cardiac hypertrophy is a key biological response to injurious stresses such as pressure overload, and when excessive, leads to heart failure. Innate immune activation by danger signals, through intracellular pattern recognition receptors such as nucleotide-binding oligomerization domain-containing protein 1 (Nod1) and its adaptor receptor-interacting protein 2 (RIP2) can play a major role in cardiac remodeling and progression to heart failure. We hypothesize that the danger signals originating from stressed mitochondria can be a major source modulator of innate immune activation, but the specific mechanism is to date unknown. Methods and results: To elucidate the contribution of Nod1/RIP2 signaling to cardiac hypertrophy, we allocated wild-type (WT), Nod1-knockout (Nod1−/−), and RIP2-knockout (RIP2−/−) mice to transverse aortic constriction (TAC) or sham operations. Nod1 and RIP2 proteins were rapidly unregulated in the heart after TAC, and this was paralleled by increases in mitochondrial proteins, including mitochondrial antiviral signaling protein (MAVS). Nod1−/− and RIP2−/− mice subjected to TAC exhibited better survival and cardiac function, and markedly decreased cardiac hypertrophy. The knock-out animals also had lower lung/body weight ratio after TAC than WT mice, indicating less lung congestion and heart failure. Downstream signal pathways for inflammation, fibrosis, apoptosis, NF-kB translocation and MAPK-GATA4/p300 activation were all reduced in both Nod1−/− and RIP2 −/− mice after TAC compared with WT mice. Co-immunoprecipitation of extracted cardiac proteins and immunofluorescent staining showed that RIP2, Nod1 and MAVS together form an interacting complex, which constitutes a potent activator of NF-kB signaling. Importantly, knocking down of MAVS expression with siRNA rapidly attenuated the complex formation, NF-kB signaling and myocyte hypertrophy.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".