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Updated: Aug 3, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus
Hye Won Lee1, Sun Ju Lee1, Min Young Lee1
1Biomedical Research Institute, Department of Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea.
Background:
Diabetic cardiomyopathy (DM CMP) is defined as cardiomyocyte damage and ventricular dysfunction directly associated with diabetes independent of concomitant coronary artery disease or hypertension. Matrix metalloproteinases (MMPs), especially MMP-2, have been reported to underlie the pathogenesis of DM CMP by increasing extracellular collagen content.
Purpose:
We hypothesized that two discrete MMP-2 isoforms (full length MMP-2, FL-MMP-2; N-terminal truncated MMP-2, NTT-MMP-2) are induced by high glucose stimulation in vitro and in an experimental diabetic heart model.
Methods:
Rat cardiomyoblasts (H9C2 cells) were examined to determine whether high glucose can induce the expression of the two isoforms of MMP-2. For the in vivo study, we used the streptozotocin-induced DM mouse heart model and age-matched controls. The changes of each MMP-2 isoform expression in the diabetic mice hearts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical stains were conducted to identify the location and patterns of MMP-2 isoform expression. Echocardiography was performed to compare and analyze the changes in cardiac function induced by diabetes.
Results:
Quantitative RT-PCR and immunofluorescence staining showed that the two MMP-2 isoforms were strongly induced by high glucose stimulation in H9C2 cells. Although no definite histologic features of diabetic cardiomyopathy were observed in diabetic mice hearts, left ventricular systolic dysfunction was determined by echocardiography. Quantitative RT-PCR and IHC staining showed this abnormal cardiac function was accompanied with the increases in the mRNA levels of the two isoforms of MMP-2 and related to intracellular localization.
Conclusion:
Two isoforms of MMP-2 were induced by high glucose stimulation in vitro and in a Type 1 DM mouse heart model. Further study is required to examine the role of these isoforms in DM CMP.
Insights
High glucose induces two matrix metalloproteinase-2 (MMP-2) isoforms in diabetic cardiomyopathy models. These MMP-2 isoforms are linked to cardiac dysfunction in experimental diabetes.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Endocrinology
Background:
- Diabetic cardiomyopathy (DM CMP) involves heart muscle damage and dysfunction due to diabetes.
- Matrix metalloproteinases (MMPs), particularly MMP-2, are implicated in DM CMP pathogenesis by altering collagen content.
Purpose of the Study:
- To investigate if high glucose induces two specific MMP-2 isoforms (full-length and N-terminal truncated) in vitro and in an experimental diabetic heart.
- To understand the role of these MMP-2 isoforms in the development of diabetic cardiomyopathy.
Main Methods:
- Utilized rat cardiomyoblasts (H9C2 cells) for in vitro high glucose stimulation.
- Employed a streptozotocin-induced Type 1 diabetes mouse model for in vivo studies.
- Quantified MMP-2 isoform expression using qRT-PCR and identified their localization via immunohistochemistry.
- Assessed cardiac function using echocardiography.
Main Results:
- High glucose significantly induced both MMP-2 isoforms in H9C2 cells.
- Diabetic mice exhibited left ventricular systolic dysfunction despite lacking overt histological DM CMP features.
- Increased mRNA levels of both MMP-2 isoforms, correlated with intracellular localization, accompanied the observed cardiac dysfunction.
Conclusions:
- Two MMP-2 isoforms are induced by high glucose in vitro and in a Type 1 DM mouse model.
- Further research is needed to elucidate the specific role of these MMP-2 isoforms in diabetic cardiomyopathy.
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