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Mixed Lineage Kinase Domain-Like Pseudokinase (MLKL) Gene Expression in Human Atherosclerosis with and without Type 2
Amany Mohamed Kamal1, Samer Ahmed Sebak2, Eman Fouad Sanad1
1Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Background:
Mixed lineage kinase domain-like pseudokinase (MLKL), one of the main downstream components of the necroptosis or programmed necrosis has recently been demonstrated in advanced atherosclerotic lesions. However, its precise role in the atherosclerosis pathogenesis still requires more elucidation. Our study was set to delineate both the changes in peripheral MLKL gene expression and its influence on disease severity in atherosclerotic patients with and without type 2 diabetes mellitus.
Methods:
The study involved 50 patients (20 non-diabetics and 30 diabetics) undergoing coronary artery bypass graft and 20 apparently healthy controls. Taqman RT-PCR was used to quantify MLKL mRNA expression levels, while ELISA was employed to estimate serum insulin and high sensitivity C-reactive protein (hsCRP) levels.
Results:
Compared with the control group, MLKL gene was up regulated significantly in cardiovascular diseases (CVD; p ≤ 0.001). Higher MLKL expression was demonstrated in diabetic CVD group than non-diabetic group (p < 0.05). Correlation studies reported positive associations between MLKL and markers of dyslipidemia, inflammation, and insulin resistance. Multiple regression analysis revealed that FBG levels, hsCRP levels, and total white blood cells count were significant predictors for MLKL levels. Receiver operating characteristic curve showed a significant diagnostic value of MLKL for CVD. Moreover, regression analysis demonstrated that MLKL and hsCRP were independent predicting factors for the severity of CVD.
Conclusion:
MLKL is linked to hallmarks of atherosclerosis and could explain increased cardiovascular risk in diabetic patients. Thus, it can be a potential drug target for treatment of atherosclerotic patients.
Insights
Mixed lineage kinase domain-like pseudokinase (MLKL) is elevated in cardiovascular disease and linked to diabetes. Higher MLKL levels predict disease severity, suggesting it as a potential therapeutic target for atherosclerosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Mixed lineage kinase domain-like pseudokinase (MLKL) is implicated in necroptosis and found in atherosclerotic lesions.
- The exact role of MLKL in atherosclerosis pathogenesis requires further investigation.
- This study examines MLKL gene expression in atherosclerotic patients with and without type 2 diabetes mellitus.
Purpose of the Study:
- To investigate peripheral MLKL gene expression changes in atherosclerotic patients.
- To determine the influence of MLKL on atherosclerosis severity in diabetic and non-diabetic individuals.
- To explore MLKL as a potential biomarker and therapeutic target for atherosclerosis.
Main Methods:
- Quantification of MLKL mRNA levels using Taqman RT-PCR.
- Measurement of serum insulin and high sensitivity C-reactive protein (hsCRP) via ELISA.
- Analysis of patient cohorts including non-diabetics, diabetics with cardiovascular disease (CVD), and healthy controls.
Main Results:
- MLKL gene expression was significantly upregulated in CVD patients compared to controls (p ≤ 0.001).
- Diabetic CVD patients exhibited higher MLKL expression than non-diabetic patients (p < 0.05).
- MLKL positively correlated with dyslipidemia, inflammation, insulin resistance markers, and predicted CVD severity alongside hsCRP.
Conclusions:
- MLKL is associated with atherosclerosis hallmarks and may contribute to increased cardiovascular risk in diabetics.
- MLKL demonstrates significant diagnostic value for CVD.
- MLKL represents a potential therapeutic target for treating atherosclerotic patients.
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