posted on 2024-02-01, 14:46authored byZheng Lian, Shi-Ran Yu, Yu-Xia Cui, Su-Fang Li, Li−Na Su, Jun-Xian Song, Chong-Yoo Lee, Qi-Xin Chen, Hong Chen
Background: Several clinical studies have suggested that
the early
administration of statins could reduce the risk of in-hospital mortality
in acute myocardial infarction (AMI) patients. Recently, some studies
have identified that stimulating lymphangiogenesis after AMI could
improve cardiac function by reducing myocardial edema and inflammation.
This study aimed to identify the effect of rosuvastatin on postinfarct
lymphangiogenesis and to identify the underlying mechanism of this
effect. Method: Myocardial infarction (MI) was induced by ligation
of the left anterior descending coronary artery in mice orally administered
rosuvastatin for 7 days. The changes in cardiac function, pathology,
and lymphangiogenesis following MI were measured by echocardiography
and immunostaining. EdU, Matrigel tube formation, and scratch wound
assays were used to evaluate the effect of rosuvastatin on the proliferation,
tube formation, and migration of the lymphatic endothelial cell line
SVEC4-10. The expression of miR-107-3p, miR-491-5p, and VEGFR3 was
measured by polymerase chain reaction (PCR) and Western blotting.
A gain-of-function study was performed using miR-107-3p and miR-491-5p
mimics. Results: The rosuvastatin-treated mice had a significantly
improved ejection fraction and increased lymphatic plexus density
7 days after MI. Rosuvastatin also reduced myocardial edema and inflammatory
response after MI. We used a VEGFR3 inhibitor to partially reverse
these effects. Rosuvastatin promoted the proliferation, migration,
and tube formation of SVEC4-10 cells. PCR and Western blot analyses
revealed that rosuvastatin intervention downregulated miR-107-3p and
miR-491-5p and promoted VEGFR3 expression. The gain-of-function study
showed that miR-107-3p and miR-491-5p could inhibit the proliferation,
migration, and tube formation of SVEC4-10 cells. Conclusion: Rosuvastatin
could improve heart function by promoting lymphangiogenesis after
MI by regulating the miRNAs/VEGFR3 pathway.