GO:0010666 positive regulation of cardiac muscle cell apoptotic process: Signaling Pathways, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0010666 describes any process that increases the rate or extent of cardiac muscle cell apoptosis, a caspase-dependent programmed cell death pathway.
• Cardiomyocyte apoptosis is a major contributor to doxorubicin-induced cardiomyopathy, diabetic cardiomyopathy, and myocardial ischemia/reperfusion injury [1,2,3].
• Key signaling axes that positively regulate this process include TNFα-TRAF3-TAK1-MAPK, NAT10/Mybbp1a/p53, and acid sphingomyelinase-mitochondrial calcium pathways [1,2,3].
• Several interventions, including curcumin, hyperoside, and CTRP12, inhibit cardiomyocyte apoptosis through Sirt1-Foxo1, PI3K-Akt, JAK2/STAT3, and other pathways [4,5,6].
• Triad3A-mediated TLR9 degradation and ADAM17 activation are emerging regulators of cardiomyocyte death in diabetic and doxorubicin-induced cardiomyopathy [1,8].
• CRISPR knockout, point mutation, knock-in, and overexpression models are essential for dissecting causal roles of specific genes in positive regulation of cardiac muscle cell apoptosis [1,2,8].
Description
GO:0010666, positive regulation of cardiac muscle cell apoptotic process, is a Gene Ontology biological process term that captures any molecular event or signaling cascade that increases the rate or extent of programmed cell death in cardiac muscle cells. Cardiac muscle cells, or cardiomyocytes, are terminally differentiated and have very limited regenerative capacity, so their loss through apoptosis directly impairs cardiac function and contributes to heart failure [1,2]. Understanding the positive regulation of this process is therefore central to cardiovascular research, because identifying the upstream signals that trigger cardiomyocyte apoptosis can reveal therapeutic targets for preventing or slowing disease progression [3,4]. The term is defined in QuickGO as any process that increases the rate or extent of cardiac cell apoptotic process, a form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases whose actions dismantle a cardiac muscle cell and result in its death. This definition places the term at the intersection of apoptosis machinery and cardiac-specific signaling, distinguishing it from general apoptotic process terms. In practice, researchers study GO:0010666 by perturbing candidate genes with CRISPR-based knockout, point mutation, knock-in, or overexpression and measuring caspase activation, annexin V staining, TUNEL positivity, and mitochondrial dysfunction in cardiomyocytes [1,2,8]. The term is highly relevant to doxorubicin cardiotoxicity, diabetic cardiomyopathy, and myocardial infarction, where excessive cardiomyocyte apoptosis drives tissue damage and adverse remodeling [1,3,5].
positive regulation of cardiac muscle cell apoptotic process At A Glance
| GO ID | GO:0010666 |
|---|---|
| GO term | positive regulation of cardiac muscle cell apoptotic process |
| Ontology | biological_process |
| Synonym | positive regulation of cardiac muscle cell apoptosis |
| Definition | Any process that increases the rate or extent of cardiac cell apoptotic process, a form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases whose actions dismantle a cardiac muscle cell and result in its death. |
| Major function | Amplification of caspase-dependent programmed cell death in cardiomyocytes |
| Related processes | Apoptotic signaling pathway, regulation of cardiac muscle cell apoptotic process, intrinsic apoptotic signaling pathway |
| Disease relevance | Doxorubicin-induced cardiomyopathy, diabetic cardiomyopathy, myocardial ischemia/reperfusion injury, heart failure |
| Research methods | CRISPR knockout, point mutation, knock-in, overexpression, TUNEL, caspase-3 activity, flow cytometry |
What Is GO:0010666?
GO:0010666 is a biological process term that describes any process which increases the rate or extent of cardiac muscle cell apoptosis. Apoptosis is a form of programmed cell death triggered by external or internal signals that activate proteolytic caspases, which dismantle the cell and cause its death. In the cardiac context, positive regulation means that a signaling event, protein modification, or gene expression change promotes or amplifies this caspase-driven death program in cardiomyocytes. The term is not a single pathway but a functional annotation that can be assigned to diverse molecular mechanisms, including death receptor signaling, mitochondrial outer membrane permeabilization, oxidative stress responses, and transcriptional upregulation of pro-apoptotic factors [1,2,3].
Why Is positive regulation of cardiac muscle cell apoptotic process Important in Cell Biology?
GO:0010666 is critically important because cardiomyocyte apoptosis is a final common pathway of cardiac injury in many diseases, and positive regulators of this process are attractive therapeutic targets. In doxorubicin-induced cardiomyopathy, cardiomyocyte-specific knockout of ADAM17 alleviates injury by inhibiting the TNFα-TRAF3-TAK1-MAPK axis, directly demonstrating that positive regulation of apoptosis can be interrupted genetically. In diabetic cardiomyopathy, acid sphingomyelinase promotes disease by disrupting mitochondrial calcium homeostasis, and Triad3A-mediated TLR9 degradation impairs mitochondrial bioenergetics and exacerbates cardiomyopathy [3,8]. In ischemia/reperfusion injury, the NAT10/Mybbp1a/p53 axis promotes cardiomyocyte ferroptosis, a related form of regulated cell death. Conversely, protective interventions such as curcumin, hyperoside, and CTRP12 inhibit apoptosis through Sirt1-Foxo1, PI3K-Akt, JAK2/STAT3, and other pathways, showing that the process is pharmacologically tractable [4,5,6]. Because the term is defined by functional outcome rather than a single molecular mechanism, it provides a unifying framework for comparing diverse pro-apoptotic signals and for designing CRISPR-based experiments that establish causality.
• Cardiomyocyte apoptosis is a major cause of irreversible heart damage in doxorubicin cardiotoxicity.
• Positive regulators such as ADAM17 and the TNFα-TRAF3-TAK1-MAPK axis are validated therapeutic targets in cardiomyopathy.
• The NAT10/Mybbp1a/p53 axis links RNA modification and ferroptosis to cardiac ischemia/reperfusion injury.
• Acid sphingomyelinase promotes diabetic cardiomyopathy by disrupting mitochondrial calcium homeostasis.
• Curcumin inhibits cardiomyocyte apoptosis via Sirt1-Foxo1 and PI3K-Akt signaling, showing dietary compounds can modulate the process.
• Hyperoside protects against myocardial infarction by modulating JAK2/STAT3 signaling and reducing apoptosis.
• CTRP12 ameliorates lipopolysaccharide-induced cardiomyocyte injury, linking inflammation to apoptotic regulation.
• Triad3A-mediated TLR9 degradation impairs mitochondrial bioenergetics and exacerbates diabetic cardiomyopathy.
• The process is central to heart failure progression and adverse cardiac remodeling after myocardial infarction.
• CRISPR-based models enable causal testing of candidate positive regulators in cardiomyocytes [1,2,8].
What Happens During positive regulation of cardiac muscle cell apoptotic process?
Initiation by external or internal death signals
In simple terms: A stress signal tells the heart muscle cell to begin self-destruction.
Positive regulation of cardiac muscle cell apoptosis begins when external ligands such as TNFα bind death receptors, or when internal stressors such as oxidative stress, DNA damage, or calcium overload generate pro-apoptotic signals [1,3]. In doxorubicin-induced cardiomyopathy, ADAM17 activation promotes TNFα signaling, which initiates the apoptotic cascade in cardiomyocytes. Acid sphingomyelinase similarly triggers pro-apoptotic signaling in diabetic cardiomyopathy by disrupting mitochondrial calcium homeostasis. These initiation events are the first step that distinguishes positive regulation from passive cell death.
Mitochondrial outer membrane permeabilization and caspase activation
In simple terms: The cell's power plants leak death-promoting proteins that switch on the executioner enzymes.
Once pro-apoptotic signals converge on mitochondria, outer membrane permeabilization releases cytochrome c and other factors that activate caspase-9 and downstream caspase-3, the proteolytic enzymes that dismantle the cardiomyocyte [1,2]. The NAT10/Mybbp1a/p53 axis promotes cardiomyocyte ferroptosis and apoptosis in ischemia/reperfusion injury, illustrating how mitochondrial and redox pathways intersect with caspase activation. Triad3A-mediated TLR9 degradation impairs mitochondrial bioenergetics, which can lower the threshold for mitochondrial apoptosis in diabetic cardiomyopathy.
Amplification through kinase cascades
In simple terms: Enzyme relay chains boost the death signal so it cannot be ignored.
Kinase cascades amplify the initial apoptotic signal. The TNFα-TRAF3-TAK1-MAPK axis is a well-defined amplification module in doxorubicin-induced cardiomyopathy, where ADAM17 promotes TRAF3-TAK1-MAPK signaling to increase cardiomyocyte apoptosis. JAK2/STAT3 signaling is another pathway that can modulate cardiomyocyte survival or death depending on context, and hyperoside protects against myocardial infarction by influencing this pathway. These cascades provide multiple nodes for pharmacological or genetic intervention.
Execution phase and cellular dismantling
In simple terms: The cell is cut apart into neat packages for removal.
In the execution phase, active caspases cleave structural and regulatory proteins, leading to cell shrinkage, membrane blebbing, and formation of apoptotic bodies. This phase is measured experimentally by TUNEL staining, annexin V flow cytometry, and caspase-3 activity assays [1,4,5]. Curcumin reduces oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1-Foxo1 and PI3K-Akt pathways, demonstrating that the execution phase can be blocked by upstream survival signaling. CTRP12 similarly ameliorates lipopolysaccharide-induced cardiomyocyte injury, reducing apoptotic execution.
Cross-talk with ferroptosis and other regulated death modes
In simple terms: Different death programs can talk to each other and overlap.
Positive regulation of cardiac muscle cell apoptosis is not isolated from other cell death modalities. The NAT10/Mybbp1a/p53 axis promotes cardiomyocyte ferroptosis to exacerbate cardiac ischemia/reperfusion injury, showing cross-talk between apoptotic and ferroptotic machinery. Acid sphingomyelinase disruption of mitochondrial calcium homeostasis in diabetic cardiomyopathy also links calcium-dependent death signaling to apoptotic pathways. This cross-talk means that annotating a gene to GO:0010666 requires functional evidence of increased apoptotic rate, not merely association with cell death.
Key Genes Involved in GO:0010666 positive regulation of cardiac muscle cell apoptotic process
The following genes and proteins have been experimentally linked to positive regulation of cardiac muscle cell apoptotic process in the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ADAM17 | Promotes TNFα-TRAF3-TAK1-MAPK signaling in doxorubicin-induced cardiomyopathy | Cardiomyocyte-specific knockout alleviates cardiomyopathy |
| TNFα | Death receptor ligand that initiates apoptotic signaling | Upstream initiator of ADAM17-dependent apoptosis |
| TRAF3 | Adaptor in TAK1-MAPK pro-apoptotic signaling | Component of the TNFα-TRAF3-TAK1-MAPK axis |
| TAK1 | Kinase that amplifies MAPK pro-apoptotic signaling | Target for interrupting apoptotic amplification |
| MAPK | Stress kinase cascade that promotes apoptosis | Downstream effector of TNFα signaling |
| NAT10 | RNA acetyltransferase that promotes ferroptosis and apoptosis | Part of NAT10/Mybbp1a/p53 axis in I/R injury |
| Mybbp1a | Nuclear protein interacting with p53 | Component of NAT10/Mybbp1a/p53 axis |
| p53 | Tumor suppressor and transcription factor promoting apoptosis | Central node in cardiomyocyte ferroptosis/apoptosis |
| Acid sphingomyelinase | Enzyme that disrupts mitochondrial calcium homeostasis | Promotes diabetic cardiomyopathy |
| Sirt1 | Deacetylase that promotes survival signaling | Curcumin activates Sirt1-Foxo1 to inhibit apoptosis |
| Foxo1 | Transcription factor modulated by Sirt1 | Mediates curcumin anti-apoptotic effects |
| PI3K-Akt | Survival kinase pathway | Curcumin activates PI3K-Akt to inhibit apoptosis |
| JAK2 | Kinase upstream of STAT3 | Hyperoside modulates JAK2/STAT3 in myocardial infarction |
| STAT3 | Transcription factor affecting survival/apoptosis | Target of hyperoside cardioprotection |
| CTRP12 | Adipokine that ameliorates cardiomyocyte injury | Reduces LPS-induced cardiomyocyte apoptosis |
| TLR9 | Innate immune receptor degraded by Triad3A | Triad3A-mediated degradation impairs mitochondrial bioenergetics |
| Triad3A | E3 ubiquitin ligase that targets TLR9 for degradation | Exacerbates diabetic cardiomyopathy |
How Is positive regulation of cardiac muscle cell apoptotic process Regulated?
Positive regulation of cardiac muscle cell apoptotic process is controlled by a balance between pro-apoptotic and pro-survival signaling. Pro-apoptotic regulation includes the TNFα-TRAF3-TAK1-MAPK axis activated by ADAM17 in doxorubicin-induced cardiomyopathy, the NAT10/Mybbp1a/p53 axis in ischemia/reperfusion injury, and acid sphingomyelinase-mediated mitochondrial calcium disruption in diabetic cardiomyopathy. Pro-survival counter-regulation includes Sirt1-Foxo1 and PI3K-Akt pathways activated by curcumin, JAK2/STAT3 signaling modulated by hyperoside, and CTRP12-mediated protection against lipopolysaccharide injury. Triad3A-mediated K48-linked ubiquitination and degradation of TLR9 impairs mitochondrial bioenergetics and exacerbates diabetic cardiomyopathy, adding a ubiquitin-proteasome layer of regulation. These pathways converge on mitochondrial integrity and caspase activation, making the process highly responsive to both genetic and pharmacological perturbation.
positive regulation of cardiac muscle cell apoptotic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ADAM17 | Doxorubicin-induced cardiomyopathy | Cardiomyocyte-specific conditional knockout mouse |
| NAT10 | Cardiac ischemia/reperfusion injury and ferroptosis | NAT10 knockout or knockdown in cardiomyocytes |
| Acid sphingomyelinase | Diabetic cardiomyopathy and mitochondrial calcium overload | Smpd1 knockout or pharmacological inhibition |
| Triad3A | Diabetic cardiomyopathy and mitochondrial bioenergetics | Triad3A overexpression or knockout in cardiomyocytes |
| TLR9 | Inflammation-associated cardiac injury | TLR9 point mutation or knockout to block Triad3A degradation |
Doxorubicin-induced cardiomyopathy
Doxorubicin is a widely used chemotherapy drug whose clinical use is limited by cardiotoxicity. Cardiomyocyte-specific knockout of ADAM17 alleviates doxorubicin-induced cardiomyopathy by inhibiting the TNFα-TRAF3-TAK1-MAPK axis, directly demonstrating that positive regulation of cardiac muscle cell apoptosis is a causal driver of this disease. This makes ADAM17 and its downstream effectors attractive targets for cardioprotective strategies during cancer treatment.
Diabetic cardiomyopathy
Diabetic cardiomyopathy is characterized by myocardial dysfunction independent of coronary artery disease and hypertension. Acid sphingomyelinase promotes diabetic cardiomyopathy via disruption of mitochondrial calcium homeostasis, linking sphingolipid metabolism to apoptotic and mitochondrial death pathways. Triad3A-mediated K48-linked ubiquitination and degradation of TLR9 impairs mitochondrial bioenergetics and exacerbates diabetic cardiomyopathy, providing another mechanism by which positive regulation of cardiomyocyte apoptosis contributes to disease. Curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1-Foxo1 and PI3K-Akt signaling, showing that the process can be therapeutically modulated.
Myocardial infarction and ischemia/reperfusion injury
Myocardial infarction causes acute cardiomyocyte loss, and reperfusion can paradoxically exacerbate injury through apoptosis and ferroptosis. The NAT10/Mybbp1a/p53 axis promotes cardiomyocyte ferroptosis to exacerbate cardiac ischemia/reperfusion injury, highlighting cross-talk between apoptotic and ferroptotic death programs. Hyperoside protects against cardiomyocyte injury in mice with myocardial infarction by modulating JAK2/STAT3 signaling, further supporting the therapeutic relevance of targeting positive regulators of apoptosis.
Inflammation-associated cardiac injury
Systemic inflammation, such as that caused by lipopolysaccharide, can induce cardiomyocyte apoptosis. CTRP12 ameliorates lipopolysaccharide-induced cardiomyocyte injury, indicating that anti-inflammatory adipokines can counteract positive regulation of apoptosis. Triad3A-mediated TLR9 degradation links innate immune receptor turnover to mitochondrial dysfunction and diabetic cardiomyopathy, showing how inflammatory signaling intersects with apoptotic regulation.
From positive regulation of cardiac muscle cell apoptotic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is ADAM17 causally required for doxorubicin-induced cardiomyocyte apoptosis? | Cardiomyocyte-specific ADAM17 knockout mouse |
| Does NAT10 promote ferroptosis and apoptosis in ischemia/reperfusion injury? | NAT10 knockout or knockdown cardiomyocytes |
| Does acid sphingomyelinase disruption of mitochondrial calcium drive diabetic cardiomyopathy? | Acid sphingomyelinase knockout or point mutation |
| Does Triad3A-mediated TLR9 degradation exacerbate diabetic cardiomyopathy? | Triad3A overexpression and TLR9 K48-ubiquitination-deficient knock-in |
| Can Sirt1-Foxo1 activation protect against diabetic cardiomyopathy? | Sirt1 overexpression or Foxo1 point mutation |
| Does JAK2/STAT3 modulation by hyperoside reduce myocardial infarction injury? | STAT3 knockout or knock-in reporter cardiomyocytes |
How to Study the positive regulation of cardiac muscle cell apoptotic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| TUNEL staining | DNA fragmentation in apoptotic cells | Quantify cardiomyocyte apoptosis in tissue sections |
| Annexin V flow cytometry | Phosphatidylserine externalization | Measure early apoptosis in cultured cardiomyocytes |
| Caspase-3/7 activity assay | Executioner caspase activity | Confirm apoptotic execution after gene perturbation [1,4] |
| Mitochondrial calcium imaging | Mitochondrial calcium levels | Assess acid sphingomyelinase effects in diabetic cardiomyopathy |
| Seahorse oxygen consumption | Mitochondrial bioenergetics | Evaluate Triad3A/TLR9 effects on mitochondrial function |
| RNA sequencing | Global transcriptome changes | Identify apoptotic pathways after CRISPR knockout [1,2] |
| Phosphoproteomics | Kinase signaling changes | Map TNFα-TRAF3-TAK1-MAPK and JAK2/STAT3 cascades [1,5] |
| CRISPR knockout screening | Gene essentiality for apoptosis | Discover novel positive regulators in cardiomyocytes [1,8] |
Apoptosis quantification assays
TUNEL staining, annexin V flow cytometry, and caspase-3/7 activity assays are standard methods to measure the rate of cardiomyocyte apoptosis after genetic or pharmacological perturbation [1,4,5]. These assays provide the functional readout that defines positive regulation in GO:0010666. Combining multiple assays reduces false positives and distinguishes apoptosis from necrosis or ferroptosis.
Mitochondrial function and calcium imaging
Mitochondrial membrane potential, oxygen consumption rate, and mitochondrial calcium measurements are used to assess how positive regulators such as acid sphingomyelinase and Triad3A affect mitochondrial integrity [3,8]. These methods link upstream signaling to the mitochondrial pathway of apoptosis. Live-cell imaging with calcium-sensitive dyes or genetically encoded sensors can reveal dynamic changes preceding caspase activation.
Transcriptomics and proteomics
RNA sequencing and quantitative proteomics can identify global changes in apoptotic and survival pathways after CRISPR perturbation of candidate genes [1,2]. Pathway enrichment analysis helps map differentially expressed genes to GO:0010666 and related terms. Phosphoproteomics is particularly useful for dissecting kinase cascades such as TNFα-TRAF3-TAK1-MAPK and JAK2/STAT3 [1,5].
CRISPR-based functional genomics
CRISPR knockout, point mutation, knock-in, and overexpression models allow causal testing of specific genes in positive regulation of cardiac muscle cell apoptosis [1,2,8]. Pooled CRISPR screens can identify novel regulators, while single-gene editing validates hits in isogenic cardiomyocyte backgrounds. These approaches are essential for distinguishing correlation from causation in disease models [1,8].
How CRISPR Can Be Used to Study GO:0010666 positive regulation of cardiac muscle cell apoptotic process
Knockout
CRISPR knockout is used to delete candidate positive regulators such as ADAM17, NAT10, or Triad3A and test whether cardiomyocyte apoptosis is reduced in disease models [1,2,8]. Cardiomyocyte-specific conditional knockout of ADAM17 alleviates doxorubicin-induced cardiomyopathy, providing direct causal evidence for its role in GO:0010666. Knockout models are also valuable for validating hits from CRISPR screens and for testing epistasis between pathways.
Point Mutation
Point mutation knock-in can dissect specific phosphorylation, ubiquitination, or catalytic sites within apoptotic regulators. For example, mutating the catalytic domain of acid sphingomyelinase or the K48-ubiquitination sites on TLR9 can reveal which molecular features are required for positive regulation of cardiomyocyte apoptosis [3,8]. Point mutations are also useful for creating constitutively active or dominant-negative alleles of kinases such as TAK1 or JAK2 [1,5].
Knock-in
Knock-in of reporter genes, epitope tags, or human disease variants allows precise tracking and functional analysis of apoptotic regulators in cardiomyocytes. Tagged knock-in of ADAM17 or NAT10 enables proteomic and imaging studies of their interactions and localization during apoptosis [1,2]. Knock-in of disease-associated variants can model patient-specific mechanisms of cardiomyopathy.
Overexpression
Overexpression of candidate genes such as Triad3A, acid sphingomyelinase, or CTRP12 can test sufficiency for promoting or inhibiting cardiomyocyte apoptosis [3,6,8]. Overexpression models are particularly useful when knockout is lethal or when gain-of-function is the relevant disease mechanism. Combining overexpression with apoptosis assays provides a complementary approach to knockout studies.
How EDITGENE Supports positive regulation of cardiac muscle cell apoptotic process Research
Researchers studying positive regulation of cardiac muscle cell apoptotic process-related genes often need to determine whether a candidate gene is causally involved in promoting or inhibiting cardiomyocyte death. Establishing causality requires precise genetic perturbation in relevant cardiac cell models, followed by functional apoptosis assays and pathway analysis. EDITGENE provides end-to-end CRISPR services to accelerate this discovery process.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of cardiac muscle cell apoptotic process research.
Frequently Asked Questions About positive regulation of cardiac muscle cell apoptotic process
What is GO:0010666 positive regulation of cardiac muscle cell apoptotic process?
GO:0010666 is a Gene Ontology biological process term describing any process that increases the rate or extent of cardiac muscle cell apoptosis, a caspase-dependent programmed cell death pathway.
What genes are involved in positive regulation of cardiac muscle cell apoptotic process?
Key genes include ADAM17, TNFα, TRAF3, TAK1, MAPK, NAT10, Mybbp1a, p53, acid sphingomyelinase, Sirt1, Foxo1, PI3K-Akt, JAK2, STAT3, CTRP12, TLR9, and Triad3A [1,2,3,4,5,6,8].
How is cardiac muscle cell apoptosis regulated?
It is regulated by a balance of pro-apoptotic signals such as TNFα-TRAF3-TAK1-MAPK and NAT10/Mybbp1a/p53, and pro-survival signals such as Sirt1-Foxo1, PI3K-Akt, and JAK2/STAT3 [1,2,4,5].
What diseases involve positive regulation of cardiac muscle cell apoptosis?
Doxorubicin-induced cardiomyopathy, diabetic cardiomyopathy, myocardial infarction, ischemia/reperfusion injury, and inflammation-associated cardiac injury all involve this process [1,2,3,5,6,8].
How do researchers study GO:0010666?
Researchers use CRISPR knockout, point mutation, knock-in, and overexpression models combined with TUNEL, annexin V, caspase activity, mitochondrial function, and omics assays [1,2,3,8].
What is the role of ADAM17 in cardiomyocyte apoptosis?
ADAM17 promotes the TNFα-TRAF3-TAK1-MAPK axis in doxorubicin-induced cardiomyopathy, and its cardiomyocyte-specific knockout alleviates disease.
How does NAT10 regulate cardiac cell death?
NAT10, together with Mybbp1a and p53, promotes cardiomyocyte ferroptosis and apoptosis to exacerbate cardiac ischemia/reperfusion injury.
Can curcumin inhibit cardiomyocyte apoptosis?
Yes, curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1-Foxo1 and PI3K-Akt signaling pathways.
What is the role of Triad3A in diabetic cardiomyopathy?
Triad3A mediates K48-linked ubiquitination and degradation of TLR9, impairing mitochondrial bioenergetics and exacerbating diabetic cardiomyopathy.
What CRISPR models are available for studying cardiac apoptosis?
Knockout, point mutation, knock-in, tagged knock-in, and overexpression models can be generated in cardiomyocyte-relevant cell lines and primary cells [1,2,8].
Conclusion
GO:0010666 positive regulation of cardiac muscle cell apoptotic process is a central biological process in cardiovascular disease, integrating death receptor signaling, mitochondrial dysfunction, kinase cascades, and transcriptional programs. The verified literature demonstrates that ADAM17, NAT10, acid sphingomyelinase, Triad3A, and other regulators causally promote cardiomyocyte apoptosis in doxorubicin-induced, diabetic, and ischemic heart disease [1,2,3,8]. Conversely, Sirt1-Foxo1, PI3K-Akt, JAK2/STAT3, and CTRP12-mediated pathways can inhibit this process, highlighting therapeutic opportunities [4,5,6]. CRISPR-based knockout, point mutation, knock-in, and overexpression models are indispensable for establishing causality and for discovering new drug targets. EDITGENE provides comprehensive services to support these studies from model generation to bioinformatics analysis.
References
- 1. Xie L et al.. 2024. Cardiomyocyte-specific knockout of ADAM17 alleviates doxorubicin-induced cardiomyopathy via inhibiting TNFα-TRAF3-TAK1-MAPK axis.. Signal Transduct Target Ther 9(1):273 PMID: 39406701
- 2. Qu Z et al.. 2024. The positive feedback loop of the NAT10/Mybbp1a/p53 axis promotes cardiomyocyte ferroptosis to exacerbate cardiac I/R injury.. Redox Biol 72:103145 PMID: 38583415
- 3. Wei Y et al.. 2025. Acid sphingomyelinase promotes diabetic cardiomyopathy via disruption of mitochondrial calcium homeostasis.. Cardiovasc Diabetol 24(1):272 PMID: 40640752
- 4. Ren BC et al.. 2020. Curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1-Foxo1 and PI3K-Akt signalling pathways.. J Cell Mol Med 24(21):12355-12367 PMID: 32961025
- 5. Rao T et al.. 2024. Exploring the role and mechanism of hyperoside against cardiomyocyte injury in mice with myocardial infarction based on JAK2/STAT3 signaling pathway.. Phytomedicine 128:155319 PMID: 38518637
- 6. Zhou MQ et al.. 2020. CTRP12 Ameliorated Lipopolysaccharide-Induced Cardiomyocyte Injury.. Chem Pharm Bull (Tokyo) 68(2):133-139 PMID: 32009080
- 8. Kong C et al.. 2024. Triad3A-Mediated K48-Linked ubiquitination and degradation of TLR9 impairs mitochondrial bioenergetics and exacerbates diabetic cardiomyopathy.. J Adv Res 61:65-81 PMID: 37625569
