Myocardial angiogenesis induced by exercise training involves a regulatory mechanism mediated by kinin receptors

ABSTRACT

Objective:

To demonstrate that the kallikrein-kinin system (KKS) is upstream of angiogenic signaling pathway, and to determine the role of the kinin B1 and B2 receptors in myocardial angiogenesis induced by exercise training.

Methods:

Forty Wistar rats were randomly assigned to an exercise control (EC) group, a B1 receptor antagonist (B1Ant) group, a B2 receptor antagonist (B2Ant) group, and a double receptor antagonist ((B1+ B2)Ant) group. A myocardial infarction model was employed. Animals in all groups received 30 min of exercise training for 4 weeks. The expression of VEGF and eNOS, capillary supply, and apoptosis rate were evaluated.

Results:

The mRNA and protein expression of VEGF and eNOS showed similar trends in all groups, and were lowest in the (B1+ B2) Ant group, and highest in the EC group. Levels of VEGF and eNOS mRNA were significantly lower in the B1Ant group than in the B2Ant group (p< .001 and p< .05, respectively). VEGF and eNOS protein in the B1Ant group was also significantly lower (p< .01 and p< .05, respectively) than in the B2Ant group. The capillary numbers in the (B1+ B2) Ant group were significantly lower than in the EC group (395.8 ± 105 vs. 1127.9 ± 192.98, respectively). The apoptosis rate of cardiomyocytes was highest in the (B1+ B2) Ant group.

Conclusion:

KKS may act as an upstream signal transduction pathway for angiogenic factors in myocardial angiogenesis. The B1 and B2 receptors exert additive effects, and the B1 receptor has the most prominent role in mediating KKS-induced myocardial angiogenesis.

KEYWORDS:

• Angiogenesis
• kallikrein-kinin system
• kinin B1 receptor
• kinin B2 receptor
• exercise training
• myocardial infarction
• VEGF
• eNOS

Acknowledgments

This study was approved by the Ethics Committee of Affiliated Zhongshan Hospital of Dalian University.

Disclosure statement

The authors have declared that no competing interests exist.

Statement of animal rights

The study protocol complied with the Guide for the Care and Use of Laboratory Animals published by the

U.S. National Institutes of Health (NIH Publication no. 85–23, revised 1996).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant No. 81071598]. Construction founds of key medicial disciplines in Longhua district, Shenzhen [MKD202007090206]; National Natural Science Foundation of China [81071598]; Construction founds of key medicial disciplines in Longhua district, Shenzhen [MKD202007090206].