A study on the mechanism of accelerated vascular injury induced by sodium loading

背景众所周知，过量摄入钠是心血管疾病的危险因素，因为它会升高血压。然而，据报道，钠负荷促进心血管疾病独立于其对血压的影响。方法和结果我们使用大鼠股动脉的钢丝损伤模型来检测钙调神经磷酸酶在钠负荷诱导的血管炎症中的作用。在钠负荷的正常血压大鼠如Wistar京都（WKY）和Dahl盐耐（DR）大鼠中，主动脉中的钙调神经磷酸酶活性显著高于对照WKY和DR大鼠。与对照WKY和DR大鼠相比，钠负荷WKY和DR大鼠的新生内膜形成也显著增加。表达钙调神经磷酸酶显性阴性突变体（AdCalAΔ C92 Q）的腺病毒基因转移显著抑制了钠负荷WKY和DR大鼠的新生内膜形成，其水平与对照WKY和DR大鼠相似。在高血压大鼠中，如自发性高血压大鼠和钠负荷的Dahi盐敏感大鼠，钙调神经磷酸酶活性和新生内膜形成更显著增强; AdCalAΔ C92 Q感染显著抑制这些大鼠的新生内膜形成。结论钠负荷可促进正常和高血压大鼠血管炎症反应，钙调神经磷酸酶在此过程中起关键作用。

Background It is well known that an excessive intake of sodium is a risk factor for cardiovascular disease because it raises the blood pressure. However, sodium loading reportedly promotes cardiovascular disease independently of its effect on blood pressure. Methods and Results We examined the role of calcineurin in sodium loading-induced vascular inflammation using a wire injury model of the rat femoral artery. Calcineurin activity in the aorta was significantly higher in sodium-loaded normotensive rats such as Wistar Kyoto(WKY) and Dahl salt-resistant(DR) rats than that in control WKY and DR rats. Neointimal formation was also significantly enhanced in sodium-loaded WKY and DR rats as compared with control WKY and DR rats. Gene transfer of an adenovirus expressing a dominant-negative mutant of calcineurin(AdCalAΔC92Q) significantly suppressed neointimal formation in sodium-loaded WKY and DR rats to a level similar to that observed in control WKY and DR rats. Calcineurin activity and neointimal formation were more significantly enhanced in hypertensive rats, such as spontaneously hypertensive rats and sodium-loaded Dahi salt-sensitive rats ; AdCalAΔC92Q infection significantly suppressed neointimal formation in these rats. Conclusions These results suggest that sodium loading promotes vascular inflammation in normotensive and hypertensive rats and that calcineurin plays a pivotal role in this process.