Kunes Jaroslav, Zicha Josef
Cardiovascular Research Centre and Institute of Physiology, AS CR, Videnska 1083, 142 20 Prague 4, Czech Republic.
Clin Sci (Lond). 2006 Nov;111(5):295-305. doi: 10.1042/CS20050271.
Genetic studies in humans and rodent models should help to identify altered genes important in the development of cardiovascular diseases, such as hypertension. Despite the considerable research effort, it is still difficult to identify all of the genes involved in altered blood pressure regulation thereby leading to essential hypertension. We should keep in mind that genetic hypertension and other cardiovascular diseases might develop as a consequence of early errors in well-co-ordinated systems regulating cardiovascular homoeostasis. If these early abnormalities in the ontogenetic cascade of expression of genetic information occur in critical periods of development (developmental windows), they can adversely modify subsequent development of the cardiovascular system. The consideration that hypertension and/or other cardiovascular diseases are late consequences of abnormal ontogeny of the cardiovascular system could explain why so many complex interactions among genes and environmental factors play such a significant role in the pathogenesis of these diseases. The detailed description and precise time resolution of major developmental events occurring during particular stages of ontogeny in healthy individuals (including advanced knowledge of gene expression) could facilitate the detection of abnormalities crucial for the development of cardiovascular alterations characteristic of the respective diseases. Transient gene switch-on or switch-off in specific developmental windows might be a useful approach for in vivo modelling of pathological processes. This should help to elucidate the mechanisms underlying cardiovascular diseases (including hypertension) and to develop strategies to prevent the development of such diseases.
对人类和啮齿动物模型的基因研究应有助于识别在心血管疾病（如高血压）发展过程中起重要作用的基因改变。尽管进行了大量研究，但仍难以确定所有参与血压调节改变从而导致原发性高血压的基因。我们应牢记，遗传性高血压和其他心血管疾病可能是调节心血管稳态的协调系统早期错误的结果。如果这些基因信息表达个体发生级联中的早期异常发生在发育的关键时期（发育窗口），它们可能会对心血管系统的后续发育产生不利影响。高血压和/或其他心血管疾病是心血管系统个体发生异常的晚期后果这一观点，可以解释为什么基因与环境因素之间如此多的复杂相互作用在这些疾病的发病机制中发挥着如此重要的作用。对健康个体个体发生特定阶段发生的主要发育事件进行详细描述和精确的时间解析（包括基因表达的先进知识），可能有助于检测对各自疾病特征性心血管改变发展至关重要的异常情况。在特定发育窗口中短暂的基因开启或关闭可能是体内病理过程建模的一种有用方法。这应有助于阐明心血管疾病（包括高血压）的潜在机制，并制定预防此类疾病发展的策略。
