Pathophysiological role of mast cells in cardiovascular diseases.

肥大细胞是一种多能炎性细胞，表达多种生物活性因子，如细胞因子、生长因子、蛋白酶等。肥大细胞位于心血管组织中。然而，肥大细胞在心血管疾病发病机制中的作用尚不清楚我们目前的研究试图通过分析自发性高血压大鼠（SHR）来阐明肥大细胞的作用，这种大鼠已知会发生遗传性高血压、心脏肥厚和心力衰竭组织化学分析显示，高血压前期（2周龄）SHR大鼠心血管组织肥大细胞数量明显高于正常对照WKY大鼠，肥大细胞是产生tnf - α和乳糜酶的主要细胞之一。此外，SHR大鼠心血管组织中tnf - α、NF-kB、IL-6、SCF和c-kit mRNA水平高于WKY大鼠为了进一步研究肥大细胞在SHR中的作用，我们评估了肥大细胞稳定剂曲尼司特对SHR高血压发展的治疗作用。从2周龄开始，给SHR口服孟鲁司特（300 mg/kg/天）10周曲尼司特治疗可显著抑制高血压的发展，并减少SHR心血管组织中肥大细胞的数量。曲尼司特还能抑制血管周围纤维化和血管增厚总之，我们的研究结果支持心血管组织肥大细胞的激活可能在心血管疾病的发病机制中起关键作用的假设。

1 Mast cells are multi-potent inflammatory cells, which express numerous bioactive factors, such as cytokines, growth factors, and proteases. Mast cells are known to locate in cardiovascular tissues. However, the role of mast cells on the pathogenesis of cardiovascular disease is unknown.2 Our present study attempted to clarify the role of mast cells by analyzing spontaneously hypertensive rats (SHR), which is known to develop genetically hypertension, cardiac hypertrophy, and heart failure.3 Histochemical analysis revealed that the number of mast cells in the cardiovascular tissues of prehypertensive (2 weeks-old) SHR was significantly higher than that of normal control WKY rats, and mast cells are one of the major cells producing TNF-alpha and chymase. Furthermore, TNF-alpha,NF-kB,IL-6,SCF and c-kit mRNA levels in the cardiovascular tissues in SHR were higher than those in WKY rats.4 To further investigate the role of mast cells in SHR, we evaluated the therapeutic effects of a mast cell stabilizer, tranilast, on the development of hypertension in SHR. Montelukast (300 mg/kg/day) was orally administered to SHR for 10 weeks, starting at the age of 2 weeks.5 Treatment with tranilast significantly inhibit the development of hypertension, and decreased the number of mast cells in cardiovascular tissues in SHR. Tranilast also suppressed the perivascular fibrosis and vascular thickening.6 In conclusion, our results support the hypothesis that activation of mast cells in cardiovascular tissues may play a key role in the pathogenesis of cardiovascular diseases.