Role of mast cells in pulmonary hypertension with left heart disease

Whole rat genome microarray analyses were performed in lung homogenates of three rats with established PH following supracoronary aortic banding and in three sham-operated controls. Out of a total of 28,000 analysed genes, differential expression defined as 2-fold change with p<0.05 was evident for 120 genes. Of these, 76 were upregulated and 44 downregulated in aortic banding compared with control lungs gene. Enrichment analysis revealed regulation of mast cell specific genes - 13 out of 20 genes were significantly upregulated in aortic banding compared with control lungs. To test for a putative functional role of mast cells in lung vascular remodelling and PH in LHD, we applied a pharmacological approach by treatment of aortic banding rats with the mast cell stabiliser ketotifen. Microarray analysis then compared rats that were treated with untreated.本研究对经冠状动脉上主动脉缩窄术造模成功的3只肺动脉高压（Pulmonary Hypertension, PH）模型大鼠的肺匀浆，以及3只假手术对照大鼠的肺匀浆，开展了全大鼠基因组微阵列分析。在总计分析的28000个基因中，以2倍表达差异且p<0.05作为差异表达判定标准，共筛选得到120个差异表达基因。相较于假手术对照组肺组织，主动脉缩窄组大鼠肺组织中有76个基因表达上调，44个基因表达下调。富集分析结果显示，肥大细胞（mast cell）特异性基因存在表达调控现象：相较于对照组肺组织，主动脉缩窄组20个肥大细胞特异性基因中有13个显著上调。为验证肥大细胞在左心疾病（Left Heart Disease, LHD）相关肺血管重构及肺动脉高压中的潜在功能作用，本研究采用药理学干预手段，对主动脉缩窄术造模大鼠给予肥大细胞稳定剂酮替芬（ketotifen）干预。随后通过微阵列分析，对比了酮替芬给药组与未给药对照组大鼠的基因表达差异。