Molecular mechanism of obesity-related left ventricular systolic dysfunction in mice and application of ultrasonic strain detection technology

Obesity is a major independent risk factor for cardiovascular diseases, such as coronary heart disease. Thus, this study assessed myocardial function in obese mice using the strain technique and analyzed the differential expression of the myocardial molecular mechanism between obese and normal mice by pathology, immunofluorescence detection, and exosome microRNA (miRNA) sequencing to examine molecular changes in the obese myocardium.

In this study, 6-week-old male C57BL/6J mice (n=32) were divided into the control group (which received the control diet for 12 weeks) and the obese group (which received the high-fat diet for 12 weeks). The characteristics of the mice were evaluated using metabolic tests, a 2-dimensional (2D) strain analysis, and histopathology. Pathology, immunofluorescence detection, and miRNA sequencing of the exosomes were used to examine molecular changes in the obese myocardium.

The ventricular septum of the obese mice was significantly thickened, and the cardiomyocytes of the obese mice were increased. NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) expression was increased in the obese mice as shown by immunofluorescence (P<0.001). Left ventricular remodeling was more marked in the obese group than the control group (P<0.001). Longitudinal, circumferential and radial peak strain were significantly lower in the obese group than the control group (P<0.001). The expression of miRNA in the plasma exocrine of the obese and normal groups was examined, and 455 miRNAs were differentially expressed (of which 331 were upregulated and 124 were downregulated). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the above differentially expressed miRNAs participated in the biological regulation function and pathway of the obese myocardial contractile function, including the pathway related to the obese myocarditis response (i.e., nuclear factor kappa B-NLRP3).

The strain technique detected changes in myocardial systolic function earlier than the left ventricular ejection fraction (LVEF) in the obese mice. Left ventricular remodeling and a NLRP3-mediated inflammatory response occur in obese mice.