Mixed Lineage Kinase Domain-Like Pseudokinase (MLKL) Gene Expression in Human Atherosclerosis with and without Type 2 Diabetes Mellitus

Mohamed Kamal, Amany; Ahmed Sebak, Samer; Fouad Sanad, Eman

doi:10.52547/ibj.25.4.265

Volume 25, Issue 4 (7-2021) IBJ 2021, 25(4): 265-274 | Back to browse issues page

‎ 10.52547/ibj.25.4.265

‎ 20.1001.1.1028852.2021.25.4.4.4

PMID: 34217157

PMCID: PMC8334393

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Mohamed Kamal A, Ahmed Sebak S, Fouad Sanad E. Mixed Lineage Kinase Domain-Like Pseudokinase (MLKL) Gene Expression in Human Atherosclerosis with and without Type 2 Diabetes Mellitus. IBJ 2021; 25 (4) :265-274
URL: http://ibj.pasteur.ac.ir/article-1-3271-en.html

Mixed Lineage Kinase Domain-Like Pseudokinase (MLKL) Gene Expression in Human Atherosclerosis with and without Type 2 Diabetes Mellitus

Amany Mohamed Kamal

, Samer Ahmed Sebak

, Eman Fouad Sanad ^*

Abstract:

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.

Keywords: Atherosclerosis, Diabetes mellitus, Inflammation, Insulin resistance, Necroptosis

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Type of Study: Full Length/Original Article | Subject: Related Fields

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