- Cardiomyocyte Culture
- Cardiac Fibroblast Activation Models
- Cardiac Endothelial Cell Culture
- Cardiac Tissue/Organoid Models
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Myocardial Infarction (MI)
Myocardial Infarction (MI), or heart attack as commonly referred, occurs due to succumbing to prolonged ischemia (sustained absence of blood flow) which leads to irreversible injury of the heart muscle (myocardium). Protheragen's MyD88-targeted therapy development intends to control the inflammatory response in MI towards damage-limiting, favorable tissue repair, and preventing adverse remodeling consequences.
Introduction to Myocardial Infarction
MI is the blockage of coronary arteries, resulting in oxygen deprivation to the heart. Blood flow can be restored through reperfusion, but inflammation is initiated by damage-associated molecular patterns (DAMPs) liberated from necrotic cardiomyocytes. DAMPs activate Toll-like receptors (TLRs) and Interleukin-1 receptors (IL-1R) present on cardiac and immune cells, amplifying the MyD88 signaling cascade that ultimately poses the recruitment of leukocytes to produce inflammatory cytokines.
Pathogenesis of Myocardial Infarction
Oxygen deprivation and necrosis of cardiomyocytes occur due to blockage of coronary arteries which leads to MI, Myocardial Infarction. While critical, reperfusion triggers ischemia-reperfusion injury via DAMPs released from dying cells. DAMPs activate TLR/IL-1R-MyD88 signaling pathway in leukocytes which is the source of incoming cytokines and pro-inflammatory mediators, which results in a free-for-all body. Counteracting attempts exacerbate damage and stubborn remodeling blurring the lines of repair and destruction.
Fig.1 NLRP3/caspase-1 signaling pathway and its correlated intervention after MI. (Zhang et al., 2022)MyD88-Targeted Therapeutic Development for Myocardial Infarction
| Therapeutic Strategy | Mechanism of Action | Representative Approaches | Development Stage |
| MyD88 Pharmacologic Inhibitors | Block MyD88 dimerization to suppress TLR/IL-1R-driven NF-κB and NLRP3 inflammasome signaling, reducing inflammation and pathologic cardiac remodeling. | ST2825 (25 mg/kg), IMG2005 (1 mg/kg) – inhibit LV dilatation/hypertrophy post-MI. | Preclinical |
| MyD88-Targeted siRNA | Silence MyD88 expression to attenuate TLR4-MyD88-NF-κB signaling and inflammatory cytokine release. | MyD88 siRNA – reduces LV end-systolic/diastolic diameters without affecting infarct size. | Preclinical |
| TLR4 Antagonists | Inhibit TLR4-MyD88 pathway to suppress NF-κB activation and myocardial apoptosis. | TAK-242 (Eritoran) – reduces cleaved caspase-3, p-IκBα, and improves cardiac function in CME models. | Preclinical / Phase II/III |
| Endogenous Pathway Modulators | Downregulate MyD88-dependent signaling via endogenous inhibitors or metabolic regulators. | Adiponectin (APN) – inhibits TLR4-MyD88-NF-κB-TNF-α/IL-6. Metformin – suppresses MyD88-NF-κB axis. | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen develops advanced disease models for myocardial infarction as well as MyD88-targeted therapeutic discovery. MyD88 signaling modulator screening and evaluation against TLR/IL-1R-driven post-MI inflammation, tissue damage, and adverse remodeling, we integrate cutting-edge in vitro and in vivo models on cardiac-specific platforms.
Therapeutic Discovery Platform for Myocardial Infarction
Protheragen's MyD88 discovery platform for myocardial infarction incorporates pathway-specific modulators with cardiac injury and repair models to address the critical inflammatory phase post-MI. The platform achieves preclinical validation of therapies aimed at disrupting MyD88-dependent cytokine networks.
Disease Models Development for Myocardial Infarction
Protheragen offers full-spectrum preclinical models of Myocardial infarction and its consequences, spanning cell-based models, organoid models, and animal models that recapitulate the complexity of ischemia-reperfusion injury, inflammation, and cardiac remodeling.
- Surgical MI Models
- Sterile Inflammation Models
- Transverse Aortic Constriction
- Optogenetics-Controlled Thrombosis Model
At Protheragen, our therapeutic strategy for MyD88-driven diseases integrates disease model development, pharmacokinetics and drug safety evaluation, and investigator-initiated trials within a unified framework. By combining robust preclinical models with rigorous safety profiling and collaborative early-stage clinical studies, we accelerate the validation of MyD88-targeted therapies, ensuring rapid translation from discovery to primary clinical assessment.
If you are interested in our services, please don't hesitate to contact us.
References
- Shi, H., et al. "Astragaloside Iv Prevents Acute Myocardial Infarction by Inhibiting the Tlr4/Myd88/Nf-Kappab Signaling Pathway." J Food Biochem 45.7 (2021): e13757.
- Zhang, Q., et al. "Signaling Pathways and Targeted Therapy for Myocardial Infarction." Signal Transduct Target Ther 7.1 (2022): 78.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.