自从第一次建立了高血压基因模型，已经过去了60年以上。模型动物在理解病理生理学和有效治疗的发展中作出了重大贡献。在本综述中，作者关注两个问题：基因相关生物标志物和使用人类小鼠搜索生物标志物。作者首先概述了高血压和盐敏感模型大鼠的建立历史，及高血压病因基因和盐敏感性高血压肾脏病因理论的遗传分析进展。最近的动物模型分析加入了表观遗传改变的重要性，这是除遗传原因外高血压的另一个因素。遗传突变和对同基对动物模型进行的表观遗传分析是互补的，并应进一步开展。在表观遗传因素中，非编码RNA是一种有希望的新型“液体活检”，最初是应用于通过检测人体液体中的癌细胞衍生 DNA、RNA 或其他分子来诊断癌症，现在可适用于任何病理生理病情。然后，作者回顾了人类小鼠的有用性。很少有研究在心血管研究中使用这些小鼠，但目前的研究强调了对免疫相关疾病和在这些小鼠中搜索生物标志物的研究。讨论了在心血管研究中使用人类小鼠的前景。© 2023作者（们）。由波特兰新闻出版有限公司代表生物化学协会出版。

It has been more than 60 years since the colonized genetic model of hypertension was first established. Model animals contribute greatly to the advance of understanding of the pathophysiology and development of effective therapy. In this review, the author focuses on two points: gene-related biomarkers and the use of humanized mice to search for biomarkers. First, the author provides an overview of the history of the establishment of hypertension and salt-sensitivity model rats, as well as advances in genetic analysis of causative genes of hypertension and the theory of renal causes of salt-sensitive hypertension. The recent animal model analysis adds the notion of the importance of epigenetic alterations in addition to the genetic causes of hypertension. Both germline mutations and epigenetic analysis of congenic animal models are complementary and should carry out furtherly. Among epigenetic factors, non-coding RNA is a promising new 'liquid biopsy' which is originally applied to diagnose cancers by detecting cancer cell-derived DNA, RNA, or other molecules in a person's body fluid and now it can be applied to any pathophysiological conditions. Then, the author reviews the usefulness of humanized mice. Few studies have used such mice in cardiovascular research, but the present study highlights a study of immune-related disease and the search for biomarkers in such mice. Perspectives on using humanized mice in cardiovascular research are discussed.© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.