CARD10 deficiency attenuates myocardial infarction associated with enhanced cardiac fibroblast senescence

Q: What are the key findings of this study?

CARD10 deficiency significantly attenuated myocardial infarct size and fibrosis, restored left ventricular ejection fraction (P < 0.05), and enhanced cardiac fibroblast senescence in mice post-MI.

Q: What is the clinical evidence from this study?

Population: Myocardial infarction (n=87). Intervention: CARD10 deficiency (Card10-/- knockout) vs. Wild-type (WT) mice with myocardial infarction. Primary outcome: Post-MI cardiac remodeling and function (fibrosis, infarct size, EF, FS, LVIDd, LVIDs) and cardiac fibroblast senescence at 4 weeks (p=<0.05).

Q: What does this research mean for the field?

CARD10 deficiency attenuates myocardial injury, reduces fibrosis, and improves post-myocardial infarction cardiac function by promoting cardiac fibroblast senescence and angiogenesis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To investigate the role of CARD10 in myocardial infarction and characterize its underlying molecular and cellular mechanisms in cardiac remodeling.

Yueyue Xu; Yiwei Yao; Yueyun Zhou; Ganyi Chen; Yafeng Liu; Yunfei Jiang; Xu Cao; Wanlin Li; Yide Cao; Wen Chen; Xin Chen

doi:10.20517/jca.2026.14

August 25, 2026The Journal of Cardiovascular AgingOpen Access

CARD10 deficiency attenuates myocardial infarction associated with enhanced cardiac fibroblast senescence

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Key result

CARD10 deficiency reduces infarct size and preserves LVEF post-MI by promoting fibroblast senescence.

P<0.05
n=87

Why the study?

Caspase recruitment domain-containing protein 10 (CARD10) is implicated in mitochondrial function and aneurysm formation, but its role and underlying mechanisms in myocardial infarction were unclear.

Does CARD10 genetic deficiency attenuate myocardial injury and improve post-myocardial infarction cardiac remodeling and function in mice undergoing experimental myocardial infarction?

Key Points

To investigate the role of CARD10 in myocardial infarction and characterize its underlying molecular and cellular mechanisms in cardiac remodeling.
Analyzed CARD10 expression and localization in mouse and human cardiac tissues using Western blot and immunofluorescence.
Subjected wild-type and Card10-knockout mice to experimental myocardial infarction, assessing cardiac structure and function by echocardiography, histology, and triphenyltetrazolium chloride staining.
Assessed cellular senescence, mitochondrial dysfunction, and signaling pathways in primary cardiac fibroblasts treated with transforming growth factor-beta.
CARD10 expression increased in the infarct border zone predominantly within cardiac fibroblasts, whereas Card10 deficiency attenuated myocardial injury and improved remodeling.
Card10-deficient cardiac fibroblasts displayed elevated senescence markers, higher secretion of senescence-associated secretory phenotype factors, and conditioned media that stimulated endothelial cell proliferation and angiogenesis.
Fibroblasts lacking CARD10 exhibited severe mitochondrial dysfunction and activation of the PI3K/AKT signaling pathway.

Structured PICO

Does CARD10 genetic deficiency attenuate myocardial injury and improve post-myocardial infarction cardiac remodeling and function in mice undergoing experimental myocardial infarction?

P

Population

87 male C57BL/6 mice (Card10-/- and wild-type) subjected to LAD ligation or sham surgery and followed for up to 5 weeks, alongside paired myocardial tissue samples from 3 adult human patients (aged 44-66, 66.7% female) with end-stage ischemic cardiomyopathy undergoing heart transplantation.

E

Exposure

CARD10 genetic deficiency (Card10-/-) in mice subjected to left anterior descending coronary artery ligation, and in vitro TGF-β (10 ng/mL for 4 days) stimulation of isolated primary Card10-/- cardiac fibroblasts.

C

Comparator

Wild-type (WT) C57BL/6 mice subjected to left anterior descending coronary artery ligation or sham surgery (identical procedure without ligation), and WT primary cardiac fibroblasts.

O

Outcome

Cardiac structure, function (ejection fraction, fractional shortening, LVIDd, LVIDs by echocardiography), infarct size (by TTC staining), cardiac fibrosis (by HE and Masson's trichrome staining), and angiogenesis at 4 weeks after MI induction, alongside cardiac fibroblast senescence (SA-β-gal activity, p16, p-histone H2A.X) at 1 week post-MI and in vitro.surrogate

Main Result

p-value: p=<0.05

This preclinical study demonstrates that CARD10 deficiency attenuates post-myocardial infarction cardiac injury and remodeling by promoting cardiac fibroblast senescence and angiogenesis via mitochondrial dysfunction and PI3K/AKT signaling, identifying CARD10 as a potential therapeutic target for myocardial infarction.

Limitations

Preclinical animal and in vitro study with very small human tissue validation cohort (n = 3)
No formal sample size calculation was performed
Reliance on alpha-SMA for fibroblast co-localization, which is also expressed by vascular smooth muscle cells, requiring additional fibroblast-specific markers for definitive validation
Animal model only included 8-week-old male mice, limiting sex and age generalizability
No formal sample size calculation was performed; sample sizes were selected based on previous studies and laboratory experience.

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Implication

CARD10 inhibition merits exploration as a post-MI target; leaves open translation from murine models to human outcomes.

Abstract

Aim: Myocardial infarction (MI) causes cardiomyocyte death and triggers tissue repair and remodeling processes orchestrated by multiple cell types, particularly cardiac fibroblasts (CFs). Caspase recruitment domain-containing protein 10 (CARD10) has been implicated in mitochondrial function and aneurysm formation; however, its role in MI is not clear. To investigate the potential role of CARD10 in MI and the underlying mechanisms. Methods: CARD10 expression and localization were analyzed by Western blot and immunofluorescence in mouse and human heart tissues. CARD10-deficient (Card10-/- ) and wild-type (WT) mice were subjected to experimental MI. Cardiac structure and function were assessed by echocardiography, histological analysis, and triphenyltetrazolium chloride (TTC). Cellular senescence was evaluated in vivo and in primary CFs using senescence-associated β-galactosidase (SA-β-gal) staining and the expression of p16 and phosphorylated histone H2A.X (gH2A.X). Mitochondrial dysfunction was assessed by JC-1 staining, mitochondrial reactive oxidative species (mtROS) measurements, and transmission electron microscopy. Potential signaling pathways were investigated by Western blot analysis. Results: Following MI, CARD10 expression was increased in the infarct border zone and was predominantly localized with CFs. Card10 -/- attenuated myocardial injury, improved cardiac remodeling, and enhanced fibroblast senescence. In vitro, transforming growth factor-beta (TGF-β)-stimulated Card10-/- CFs exhibited increased senescence, accompanied by elevated secretion of senescence-associated secretory phenotype (SASP) factors. Conditioned media from Card10-/- CFs promoted endothelial cell proliferation and angiogenesis. Furthermore, Card10-/- CFs exhibited severe mitochondrial dysfunction and activation of the phosphoinositide 3-kinase (PI3K) /protein kinase B (AKT) signaling pathway. Conclusion : These findings suggest that CARD10 deficiency is associated with enhanced fibroblast senescence and improved post-MI remodeling, potentially involving mitochondrial dysfunction and PI3K/AKT signaling, highlighting CARD10 may represent a promising target for the treatment of MI.

Discussion

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Cite This Study

Xu et al. (2026) studied Myocardial infarction (n=87). CARD10 deficiency (Card10-/- knockout) vs. Wild-type (WT) mice with myocardial infarction was evaluated on Post-MI cardiac remodeling and function (fibrosis, infarct size, EF, FS, LVIDd, LVIDs) and cardiac fibroblast senescence at 4 weeks (p=<0.05). CARD10 deficiency significantly attenuated myocardial infarct size and fibrosis, restored left ventricular ejection fraction (P < 0.05), and enhanced cardiac fibroblast senescence in mice post-MI.

synapsesocial.com/papers/6ae6c34efba2b7d31da05134 https://doi.org/10.20517/jca.2026.14

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CARD10 deficiency attenuates myocardial infarction associated with enhanced cardiac fibroblast senescence

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

CARD10 deficiency attenuates myocardial infarction associated with enhanced cardiac fibroblast senescence

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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