Identification of genes relevant to the development of cardiac hypertrophy.

1. 组织肾素-血管紧张素系统与心脏肥厚。研究了肾素-血管紧张素系统各组分在主动脉-腔静脉分流诱导的大鼠肥厚心脏中的表达。我们观察到心室中表达的血管紧张素转换酶在该模型肥厚发展中的重要性。我们发现肾素在异丙肾上腺素诱导的大鼠坏死心肌的巨噬细胞/单核细胞中表达。这一发现提示巨噬细胞可能是多种病理条件下组织肾素的来源。鉴别筛选与心肌肥厚发展相关的新基因。我们发现II型组织转谷氨酰胺酶在肥厚性心脏中上调。众所周知，这种酶可以激活潜伏的tgf - β，这对心脏发育有很大的影响。用遗传学方法鉴定与心肌肥厚发生有关的新基因。我们发现大鼠1、2和8号染色体上的位点对SHR和WKY衍生的F2群体的心/体重比有显著影响。2号和8号染色体上的基因座似乎对血压有影响，1号染色体上的基因座似乎对肾功能有影响。

1. Tissue renin-angiotensin system and cardiac hypertrophy. We evaluated expression of every component of renin angiotensin system in rat hypertrophied heart induced by aorto-caval shunt. We observed the importance of angiotensin-converting enzyme expressed in the ventricles in the development of hypertrophy in this model. We found that renin was expressed in rat macrophage/monocyte cells infiltraing necrotic myocardium induced by isoproterenol administration. This findning suggests that macrophage may be a source of tissue renin in various pathological conditions.2. Identification of new genes relevant to the development of cardiac hypertrophy by differential screening. We found that type II tissue transglutaminase was up-regulated in hypertrophied heart. This enzyme has been known to activate latent TGF-beta, which has potent effects on cardiac development.3. Genetic approach to the identification of new genes relevant to the development of cardiac hypertrophy. We have found that loci in the rat chromosome 1,2 and 8 has significant effects on heart/body weight ratio in F2 population derived from SHR and WKY.The effects of the loci in chromosome 2 and 8 seem to be through the effecs on blood pressure, and the effects of the chromosome 1 locus seem to be through the effects on renal function.