Related Experiment Video

Updated: Apr 23, 2026

Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity
08:00

Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity

Published on: July 10, 2019

5.6K

Inhibition of adenosine kinase alleviates hypertrophic cardiomyopathy by ameliorating coronary microvascular

Fangfang Wan1, Bingxuan Ma1, Ziqiang Han1

  • 1State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, China.

ESC Heart Failure
|April 22, 2026
PubMed

Insights

Hypertrophic cardiomyopathy (HCM) treatment needs new targets. Adenosine kinase (ADK) is a causal gene for HCM, and inhibiting it with dabigatran shows therapeutic promise.

Area of Science:

  • Cardiovascular Genetics
  • Pharmacology
  • Molecular Medicine

Background:

  • Hypertrophic cardiomyopathy (HCM) presents significant therapeutic challenges with limited treatment options.
  • There is an urgent need to identify novel therapeutic targets for HCM.

Purpose of the Study:

  • To identify causal druggable genes for Hypertrophic cardiomyopathy (HCM) using genetic analyses.
  • To validate Adenosine kinase (ADK) as a therapeutic target and explore drug repurposing for HCM treatment.

Main Methods:

  • Mendelian randomization and colocalization analyses were performed using large-scale HCM genome-wide association data.
  • Candidate gene ADK was validated in HCM mice and endothelial cells (ECs); drug repurposing involved molecular docking, simulations, and CETSA.
  • In vitro and in vivo functional verification of ADK inhibition and potential drugs was conducted.

Main Results:

  • Adenosine kinase (ADK) was identified as a causal gene for HCM.
  • ADK inhibition in HCM mice attenuated cardiac hypertrophy, fibrosis, and microvascular dysfunction, and rescued EC function.
  • Dabigatran was identified as a high-affinity ADK binder, and its administration ameliorated microvascular dysfunction and cardiac remodeling in HCM mice.

Conclusions:

  • Adenosine kinase (ADK) is established as a viable therapeutic target for Hypertrophic cardiomyopathy (HCM).
  • Targeting ADK offers a promising strategy for managing microvascular dysfunction in HCM.
  • Drug repurposing suggests dabigatran may benefit HCM patients through ADK inhibition.
Abstract

Keywords:
Adenosine kinaseCoronary microvascular dysfunctionDabigatranDruggable genesHypertrophic cardiomyopathyMendelian randomization

More Related Videos

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes11:00

Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

Published on: September 18, 2017

9.2K
Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix10:21

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix

Published on: June 14, 2016

9.8K

Related Concept Videos

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
1.5K
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
795
Cardiomyopathy V: Interprofessional Care01:29

Cardiomyopathy V: Interprofessional Care

Managing cardiomyopathy involves addressing underlying or precipitating causes, treating heart failure with medications, and implementing dietary changes and a balanced exercise and rest regimen.Lifestyle ModificationsCardiomyopathy patients should adopt a low-sodium diet to reduce fluid retention and manage heart failure. A personalized exercise and rest plan helps maintain physical fitness without overstraining the heart. Avoiding alcohol and tobacco is essential to prevent further damage to...
743
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
930
Cardiomyopathy I: Introduction and Classification01:25

Cardiomyopathy I: Introduction and Classification

Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
809
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
767