title: Inhibitory effects of piperonylic acid on the excessive proliferation of vascular smooth muscle cells and luminal stenosis.
abstract: OBJECTIVE
  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. 21 days 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 expressions of 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 towards the intima and proliferated excessively, leading to evident neogenesis of intima and luminal stenosis. The SM-α-actin immunohistochemistry confirms that the intima contained abundant smooth muscle cells and that the expression of PCNA was high while the expression of P21 and P27 was low. The intervention of piperonylic acid significantly 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.
  
  
  CONCLUSIONS
  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 (Tab. 4, Fig. 4, Ref. 22).
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.forename: T
authors.initials: T
authors.lastname: Hong
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001024:Aortic Valve Stenosis / Q000517:prevention & control*; D001565:Benzoates / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D015870:Gene Expression; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
chemical_list: D000199:Actins; D001565:Benzoates; D018797:Cell Cycle Proteins; D018809:Proliferating Cell Nuclear Antigen; C005455:piperonylic acid