2022, Vol. 26 ›› Issue (31): 5020-5025

Effects of myeloid-derived growth factor on ventricular remodeling in aging mice

Sun Ying1, Xiang Guangda1, 2, Xu Xiaoli2   

Abstract: BACKGROUND: Aging is a predominant risk factor for many developing diseases, such as cardiovascular disease, neurodegenerative disease, and osteoporosis. Cardiovascular disease has become one of the main causes of death in the elderly.  
OBJECTIVE: To investigate the effect of myeloid-derived growth factor (MYDGF) on ventricular remodeling in aging mice.
METHODS:   15-month-old C57BL/6 mice (WT mice) and MYDGF-/- mice (KO mice) were randomly divided into four groups as follows: WT group, KO group, adeno-associated virus-green fluorescent protein group, and adeno-associated virus-MYDGF group according to the presence and absence of AAV MYDGF intervention. After the intervention for 12 weeks, the mice were subjected to cardiac ultrasound to evaluate their cardiac structure and function, and to detect various blood biochemical indicators related to cardiac function. The heart weight was weighed and the length of the tibia was measured. Hematoxylin-eosin staining and Masson staining were used to observe the degree of cardiomyocyte hypertrophy and interstitial fibrosis.  
RESULTS AND CONCLUSION: (1) Compared with the WT group, the heart weight, body weight, and heart weight to tibia length of KO group were increased (P < 0.05). (2) Left ventricular end-diastolic diameter and left ventricular end-systolic dimension in the KO group were enlarged compared with the WT group. Importantly, the ejection fractions and fractional shortening were decreased (P < 0.05). (3) Pathological results showed that compared with the WT group, the myocardial cells of the KO group were significantly enlarged, and the degree of myocardial fibrosis was deepened. (4) The sensitivity to insulin of the mice in the KO group decreased, and the rate of blood glucose decline was lower than that in the WT group (P < 0.05). There was a significant increase in brain natriuretic peptide, plasma renin activity, angiotensin II, aldosterone, and norepinephrine levels in the circulation of KO mice compared to WT mice (P < 0.05). (5) After treatment of MYDGF, the above indicators had been improved. (6) There was no significant difference in food intake, fasting blood glucose, total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and glycosylated hemoglobin levels among the groups (P > 0.05). (7) It is indicated that the lack of MYDGF can lead to pathological structural changes and decreased cardiac function in mouse cardiomyocytes, and finally cause ventricular remodeling; aging ventricular remodeling can be improved after MYDGF replenishment. MYDGF may become a new drug for the treatment of ventricular remodeling in elderly mice.
Key words: myeloid-derived growth factor, gene knockout, heart aging, cardiac hypertrophy, myocardial fibrosis, gene therapy, insulin resistance