Inhibitory effects of piperonylic acid on the excessive proliferation of vascular smooth muscle cells and luminal stenosis

Abstract

Purpose: Combining in vivo and in vitro experiments, we explored the function and mechanism of piperonylic acid inhibiteing excessive proliferation of vascular smooth muscle cells, and intimal hyperplasia and luminal stenosis after blood vessel injury.Methods: A model of rat thoracic aorta restenosis after balloon injury was constructed, intragastrically administered with piperonylic acid. 21days later, their thoracic aortas were subjected tests of morphology, SM-α-actin, proliferating cell nuclear antigen (PCNA), and expression levels of P21 and P27 by HE staining, immunohistochemistry, and computer image analysis. Results: The proliferation of vascular smooth muscle cells induced by fetal calf serum was active, and the expressionsof P21 and P27 were low. Piperonylic acid obviously promoted the protein expressions of P21 and P27 while inhibiting proliferation and DNA synthesis. After the injury of rat thoracic aorta, the cells moved towardsthe intima and proliferated excessively, leading to evident neogenesis of intima and luminal stenosis. The SM- a-actin immunohistochemistry confirms that the intima contained abundant smooth muscle cells and that theexpression of PCNA was high while the expression of P21 and P27 was low. The intervention of piperonylic acidsignificantly facilitated the gene expressions of P21 and P27, lowered the PCNA expression, and inhibited the formation of intima and the reconstruction of pathological vessels, thus remarkably suppressing luminal stenosis.Conclusion: Piperonylic acid can inhibit the excessive proliferation of vascular smooth muscle cells and the lumen narrowing after injury of blood vessels, the mechanism of which is associated with the promoted gene expressions of cell cycle key regulators P21 and P27.