Deletion of RasGRF1 Attenuated Interstitial Fibrosis in Streptozotocin-Induced Diabetic Cardiomyopathy in Mice through Affecting Inflammation and Oxidative Stress.

Abstract

BACKGROUND:

Diabetic cardiomyopathy (DCM) is characterized by cardiac fibrosis and stiffness, which often develops into heart failure. This study investigated the role of Ras protein-specific guanine nucleotide releasing factor 1 (RasGRF1) in the development of DCM.

METHODS:

Forty-eight mice were divided into four groups (n = 12 per group): Group 1: Wild-type (WT) mice, Group 2: RasGRF1 deficiency (RasGRF1-/-) mice. Group 3: Streptozotocin (STZ)-induced diabetic WT mice, Group 4: STZ-induced diabetic RasGRF1-/- mice. Myocardial functions were assessed by cardiac echography. Heart tissues from all of the mice were investigated for cardiac fibrosis, inflammation, and oxidative stress markers.

RESULTS:

Worse impaired diastolic function with elevation serum interleukin (IL)-6 was found in the diabetic group compared with the non-diabetic groups. Serum IL-6 levels were found to be elevated in the diabetic compared with the non-diabetic groups. However, the diabetic RasGRF1-/- mice exhibited lower serum IL-6 levels and better diastolic function than the diabetic WT mice. The diabetic RasGRF1-/- mice were associated with reduced cardiac inflammation, which was shown by lower invading inflammation cells, lower expression of matrix metalloproteinase 9, and less chemokines compared to the diabetic WT mice. Furthermore, less oxidative stress as well as extracellular matrix deposition leading to a reduction in cardiac fibrosis was also found in the diabetic RasGRF1-/- mice compared with the diabetic WT mice.

CONCLUSION:

The deletion of RasGRF1 attenuated myocardial fibrosis and improved cardiac function in diabetic mice through inhibiting inflammation and oxidative stress.

• Authors: Tzu-Hsien Tsai, Cheng-Jei Lin, Sarah Chua, Sheng-Ying Chung, Shyh-Ming Chen, Chien-Ho Lee, Chi-Ling Hang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 10 (Oct 10 2018) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30308936 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Cytokines
• Inflammation Mediators
• Rasgrf1 protein, mouse
• ras-GRF1
• Streptozocin
• Glucose

Topics

• Animals
• Biomarkers
• Cytokines (metabolism)
• Diabetic Cardiomyopathies (etiology, metabolism, pathology)
• Disease Models, Animal
• Extracellular Matrix (genetics, metabolism)
• Fibrosis
• Gene Deletion
• Gene Expression Regulation
• Glucose (metabolism)
• Inflammation (complications, metabolism)
• Inflammation Mediators
• Mice
• Mice, Knockout
• Myofibroblasts (metabolism)
• Oxidative Stress
• Streptozocin (adverse effects)
• ras-GRF1 (genetics, metabolism)