Abstract: Objective To investigate the impact of the sonic hedgehog (SHH) signaling pathway on angiogenesis in a rabbit model of acute myocardial infarction (AMI) by administering exogenous SHH agonists or inhibitors to activate or inhibit the pathway. Methods A rabbit AMI model was established by ligating the left anterior descending coronary artery in New Zealand white rabbits using silk thread. Rabbits were randomly divided into a control group (sham operation), a model group (AMI induced by ligation of the left anterior descending coronary artery), an agonist group (ligation of the left anterior descending coronary artery and SHH pathway activation using purmorphamine), and an inhibitor group (ligation of the left anterior descending coronary artery and SHH pathway inhibition using cyclopamine). Animals were euthanized 24 h postoperatively, and venous blood and myocardial tissue samples were collected. Serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured using enzyme-linked immunosorbent assay at 24 h postoperatively. Immunohistochemistry was employed to detect VEGF and bFGF protein expression in myocardial tissues across groups. Real-time fluorescence quantitative PCR was used to assess the mRNA expression levels of SHH, smoothened (SMO), and glioma-associated oncogene homolog 1 (Gli-1) associated with the SHH signaling pathway within myocardial tissues. Results Compared with the control group, serum VEGF and bFGF levels in the AMI model group, as measured by enzyme-linked immunosorbent assay, were significantly elevated (228.03±9.62 pg/mL vs 306.59±12.42 pg/mL; 78.25±8.35 pg/mL vs 141.80±5.58 pg/mL; P<0.05). Relative to the model group, the agonist group exhibited increased VEGF and bFGF levels (306.59±12.42 pg/mL vs 374.68±17.52 pg/mL; 141.80±5.58 pg/mL vs 167.00±9.57 pg/mL; P<0.05), while the inhibitor group showed decreased levels (306.59±12.42 pg/mL vs 266.12±13.69 pg/mL; 141.80±5.58 pg/mL vs 106.53±7.23 pg/mL; P<0.05). Compared with the control group, VEGF and bFGF protein expression levels in infarcted myocardial tissue from the model group were significantly higher (0.0951±0.0080 vs 0.1732±0.0068; 0.0636±0.0047 vs 0.1921±0.0063; P<0.05). Relative to the model group, the agonist group showed elevated VEGF and bFGF expression (0.1732±0.0068 vs 0.1963±0.0127; 0.1921±0.0063 vs 0.2320±0.0120; P<0.05), whereas the inhibitor group showed reduced expression (0.1732±0.0068 vs 0.1472±0.0416; 0.1921±0.0063 vs 0.1645±0.0048; P<0.05). Compared with the control group, mRNA expression levels of SHH, SMO, and Gli-1 in the model group were significantly increased (1±0.058 vs 1.376±0.171; 1±0.067 vs 1.202±0.877; 1±0.105 vs 1.028±0.083; P<0.05). Relative to the model group, the agonist group exhibited significantly higher expression of SHH, SMO, and Gli-1 (1.376±0.171 vs 2.165±0.267; 1.202±0.877 vs 1.990±0.152; 1.028±0.083 vs 1.619±0.174; P<0.05), while the inhibitor group showed significantly lower expression of SHH, SMO, and Gli-1 (1.376±0.171 vs 0.911±0.15; 1.202±0.877 vs 0.536±0.389; 1.028±0.083 vs 0.583±0.053; P<0.05). Conclusion Activation of the SHH signaling pathway increases the expression of angiogenic factors, thereby promoting angiogenesis following myocardial infarction. These findings suggest that the activation of SHH signaling pathway is associated with vascular regeneration in AMI.

Key words: Sonic hedgehog signaling pathway, Acute myocardial infarction, Vascular regeneration, Angiogenic factor