The effects of parathyroid hormone‐related peptide on cardiac angiogenesis, apoptosis, and function in mice with myocardial infarction

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Abstract
It is known that parathyroid hormone‐related peptide (PTHrP) contains a nuclear localization sequence (NLS, 87‐107), which, together with its C‐terminus (107‐139), has been shown to positively regulate vascular smooth muscle cell (VSMCs) proliferation and vascular neointima formation, and inhibit cellular apoptosis. The role of PTHrP in ischemic cardiac diseases remains unclear. In this study, we attempted to determine whether PTHrP 87 to 139 can play a role in promoting cardiac function via enhancing angiogenesis after myocardial infarction (MI) occurred. MI was reproduced in C57BL/6 mice using a coronary artery ligation method. In total, three groups (n = 11 per group) of animals were used, and they were received either PTHrP 87 to 139 (80 µg/kg, treatment group) or saline (MI and Sham group) subcutaneously once a day for 4 weeks after MI. To measure cardiac function, an echocardiography was generated and cardiac tissue was harvested for immunohistological studies 4 weeks after operation. Our results show that, after MI, the cardiac function of the experimental mice was significantly impaired. PTHrP 87 to 139 treatment attenuated cardiac dysfunction in MI mice. Besides, as indicated by decreased heart weight/body weight and lung weight/body weight ratio, PTHrP 87 to 139 attenuated pulmonary congestion and cardiac hypertrophy. Masson staining revealed that PTHrP 87 to 139 attenuated myocardial fibrosis after MI. Also, terminal deoxynucleotidyl transferase mediated dUTP nick‐end labeling staining and the expression of cleaved caspase 3 suggested that MI‐induced myocytes apotosis was inhibited by PTHrP 87 to 139. In addition to the significantly increased capillary density, PTHrP 87 to 139 treatment also induced p‐Akt and several angiogenic factors. In conclusion, PTHrP 87 to 139 treatment preserved cardiac function after MI, and stimulated angiogenesis via upregulating vascular endothelial growth factor and basic fibroblast growth factor (bFGF) in infarct border zone of ischemic myocardium,. These results suggest that PTHrP 87 to 139 is of therapeutic potential for MI.
Funding Information
  • National Natural Science Foundation of China (81000058)

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