Rcan1, short for Regulator of calcineurin 1, is a key endogenous inhibitor of the phosphatase calcineurin. It is involved in regulating mitochondrial function and plays a significant role in the calcineurin/NFAT transcriptional pathway. Rcan1 has been linked to multiple biological processes and is crucial in various physiological and pathological conditions [1,2,5]. Genetic models, such as knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions.

In cardiovascular diseases, RCAN1 reduction protects against atherosclerosis by reducing oxidized low-density lipoprotein uptake, while in myocardial ischemia/reperfusion injury, myocardial hypertrophy, and intramural hematoma/aortic rupture, RCAN1 has a protective effect mainly through maintaining mitochondrial function and inhibiting calcineurin and Rho kinase activity [2]. In septic cardiomyopathy, RCAN1 -/- mice showed severe cardiac function impairment, increased myocardial hypertrophy and fibrosis, and aggravated mitochondrial injury, indicating that RCAN1 deficiency exacerbates sepsis-induced cardiac remodeling and dysfunction [4]. In diabetic cardiomyopathy, knockdown of RCAN1 improved cardiac dysfunction, lipid accumulation, and mitochondrial fission in db/db mice [3].

In conclusion, Rcan1 plays essential roles in multiple biological processes, especially in cardiovascular and metabolic-related diseases. The use of KO or CKO mouse models has revealed its significance in maintaining normal physiological functions and its potential as a therapeutic target in diseases such as cardiovascular diseases, sepsis-related cardiac remodeling, and diabetic cardiomyopathy.

References:

1. Lao, Mengyi, Zhang, Xiaozhen, Yang, Hanshen, Bai, Xueli, Liang, Tingbo. 2022. RCAN1-mediated calcineurin inhibition as a target for cancer therapy. In Molecular medicine (Cambridge, Mass.), 28, 69. doi:10.1186/s10020-022-00492-7. https://pubmed.ncbi.nlm.nih.gov/35717152/

2. Wang, Shuai, Wang, Yuqing, Qiu, Kaixin, Zhu, Jin, Wu, Yili. 2020. RCAN1 in cardiovascular diseases: molecular mechanisms and a potential therapeutic target. In Molecular medicine (Cambridge, Mass.), 26, 118. doi:10.1186/s10020-020-00249-0. https://pubmed.ncbi.nlm.nih.gov/33267791/

3. Shu, Songren, Cui, Hao, Liu, Zirui, Hu, Shengshou, Song, Jiangping. 2024. Suppression of RCAN1 alleviated lipid accumulation and mitochondrial fission in diabetic cardiomyopathy. In Metabolism: clinical and experimental, 158, 155977. doi:10.1016/j.metabol.2024.155977. https://pubmed.ncbi.nlm.nih.gov/39053690/

4. Zhuang, Jinqiang, Chen, Liming, Li, Gongke, Wang, Shijun, Yuan, Ruijun. 2022. RCAN1 deficiency aggravates sepsis-induced cardiac remodeling and dysfunction by accelerating mitochondrial pathological fission. In Inflammation research : official journal of the European Histamine Research Society ... [et al.], 71, 1589-1602. doi:10.1007/s00011-022-01628-5. https://pubmed.ncbi.nlm.nih.gov/36305917/

5. Peiris, Heshan, Keating, Damien J. 2017. The neuronal and endocrine roles of RCAN1 in health and disease. In Clinical and experimental pharmacology & physiology, 45, 377-383. doi:10.1111/1440-1681.12884. https://pubmed.ncbi.nlm.nih.gov/29094385/