Nppa-KO Mouse

Nppa, which encodes atrial natriuretic peptide (ANP), is a gene of great significance in the cardiovascular system. ANP regulates salt-water balance and blood pressure by promoting renal sodium and water excretion and vasodilation. It also has anti-hypertrophic functions in the heart independent of its blood-pressure-lowering effects [4].

In Nppa knockout mice, ischemia-reperfusion (I/R) leads to an increased infarct size and reduced autophagy, indicating that Nppa plays a role in protecting the heart during I/R through autophagy activation [3]. In addition, the deletion of NPPA-AS1, an lncRNA related to Nppa, promotes cardiomyocyte proliferation and has a therapeutic effect against myocardial infarction in adult mice, suggesting an indirect role of Nppa-related molecules in cardiac regeneration [1]. In the Chinese Han population, the Nppa gene polymorphism rs5063 is associated with serum ANP levels, and ANP levels are prospectively associated with hypertension [2]. Also, Nppa promoter hypomethylation is associated with an increased future risk of central obesity in Chinese adults, indicating its potential role in obesity-related mechanisms [5].

In conclusion, Nppa is crucial for cardiovascular function, especially in maintaining heart health during stress and regulating blood pressure and body weight. Studies using gene knockout mouse models have provided insights into its role in heart-related diseases such as myocardial infarction, hypertension, and central obesity, helping to understand the underlying molecular mechanisms and potentially providing new targets for treatment.

References:

1. Fu, Wenbin, Ren, Hongmei, Shou, Jialing, Zeng, Chunyu, Wang, Wei Eric. 2022. Loss of NPPA-AS1 promotes heart regeneration by stabilizing SFPQ-NONO heteromer-induced DNA repair. In Basic research in cardiology, 117, 10. doi:10.1007/s00395-022-00921-y. https://pubmed.ncbi.nlm.nih.gov/35247074/

2. Zhang, Huan, Mo, Xingbo, Zhou, Zhengyuan, Guo, Zhirong, Zhang, Yonghong. 2019. Associations among NPPA gene polymorphisms, serum ANP levels, and hypertension in the Chinese Han population. In Journal of human hypertension, 33, 641-647. doi:10.1038/s41371-019-0219-6. https://pubmed.ncbi.nlm.nih.gov/31341238/

3. Forte, Maurizio, Marchitti, Simona, Di Nonno, Flavio, Rubattu, Speranza, Sciarretta, Sebastiano. 2022. NPPA/atrial natriuretic peptide is an extracellular modulator of autophagy in the heart. In Autophagy, 19, 1087-1099. doi:10.1080/15548627.2022.2115675. https://pubmed.ncbi.nlm.nih.gov/35998113/

4. Song, Wei, Wang, Hao, Wu, Qingyu. 2015. Atrial natriuretic peptide in cardiovascular biology and disease (NPPA). In Gene, 569, 1-6. doi:10.1016/j.gene.2015.06.029. https://pubmed.ncbi.nlm.nih.gov/26074089/

5. Li, Jing, Zhu, Jinhua, Zhang, Qiu, Wu, Lei, Peng, Hao. 2021. NPPA Promoter Hypomethylation Predicts Central Obesity Development: A Prospective Longitudinal Study in Chinese Adults. In Obesity facts, 15, 257-270. doi:10.1159/000521295. https://pubmed.ncbi.nlm.nih.gov/34875662/