Disease Information

General Information of the Disease (ID: DIS00290)

• Name: Myocardial infarction
• ICD: ICD-11: BA41

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Aspirin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Prostaglandin-endoperoxide synthase 1 (PTGS1) [1]

• Resistant Disease: Acute myocardial infarction [ICD-11: BA41.1]
• Molecule Alteration: Missense mutation; p.C50T+p.A842G+p.A1676G
• Resistant Drug: Aspirin
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The following factors contribute to aspirin resistance: the COX-1 polymorphisms of C50T, -A842G, and A1676G; the COX-2 polymorphism of -765.

Clopidogrel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) [1]

• Resistant Disease: Acute myocardial infarction [ICD-11: BA41.1]
• Molecule Alteration: SNP; CYP2C19*2+CYP2C19*3
• Resistant Drug: Clopidogrel
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: We defined CYP2C19*2 and CYP2C19*3 as CYP2C19 loss-of-function alleles (LoFA), indicating possible clopidogrel resistance.

Hydrogen peroxide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Taurine up-regulated 1 (TUG1) [2]

• Resistant Disease: Myocardial infarction [ICD-11: BA41.0]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Hydrogen peroxide
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: miR-9/KLF5 signaling pathway; Inhibition; hsa05206
• Experiment for Molecule Alteration: Luciferase assay; Knockdown assay; Overexpression assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The long non-coding RNA TUG1-miR-9a-5p axis contributes to ischemic injuries by promoting cardiomyocyte apoptosis via targeting KLF5.

Investigative Drug(s) 2 drug(s) in total

Chembl2042164

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Maternally expressed 3 (MEG3) [3]

• Resistant Disease: Myocardial infarction [ICD-11: BA41.0]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Chembl2042164
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Primary neonatal mice ventricular myocytes; N.A.; .; N.A.
• In Vivo Model: C57/BL6J mice myocardial infarction model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Knockdown assay
• Mechanism Description: Long non-coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress-mediated apoptosis by targeting p53 following myocardial infarction.

Tanshinone IIA

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA (AK003290) [4]

• Resistant Disease: Acute myocardial infarction [ICD-11: BA41.1]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Tanshinone IIA
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: H9C2 cells; Ovary; Cricetulus griseus (Chinese hamster); CVCL_A0TS
• In Vivo Model: I/R female C57BL/6 mice model; Mus musculus
• Experiment for Molecule Alteration: Knockdown assay; qRT-PCR; Western bloting analysis; RNA pull down assay; FISH assay; Luciferase assay
• Experiment for Drug Resistance: Flow cytometry assay; LDH and MDA detection assay; ROS detection assay; Dual-Luciferase assay
• Mechanism Description: TSA exerts the protective role against H/R induced apoptosis, oxidative and MMP loss of cardiomyocytes via regulating AK003290 and miR-124-5p signaling.

References

• Ref 1: Assessment of Risk Factors for Drug Resistance of Dual Anti Platelet Therapy After PCI .Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296221083674. doi: 10.1177/10760296221083674. 10.1177/10760296221083674
• Ref 2: The long non-coding RNA TUG1-miR-9a-5p axis contributes to ischemic injuries by promoting cardiomyocyte apoptosis via targeting KLF5Cell Death Dis. 2019 Dec 2;10(12):908. doi: 10.1038/s41419-019-2138-4.
• Ref 3: Long non-coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress-mediated apoptosis by targeting p53 following myocardial infarctionJ Cell Mol Med. 2019 Dec;23(12):8369-8380. doi: 10.1111/jcmm.14714. Epub 2019 Oct 20.
• Ref 4: Tanshinone IIA alleviates hypoxia/reoxygenation induced cardiomyocyte injury via lncRNA AK003290/miR-124-5p signalingBMC Mol Cell Biol. 2020 Mar 27;21(1):20. doi: 10.1186/s12860-020-00264-3.