Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is a key part of the renin-angiotensin system (RAS). It counter-regulates the RAS by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, maintaining homeostasis and protecting against lung, heart, and kidney injury. It also helps in amino-acid membrane transport [1].

ACE2 has been a focus in COVID-19 research as it serves as the receptor for SARS-COV-2. Soluble ACE2 (sACE2), which is shed from the membrane, can also act as a receptor for the virus, mediating its entry into cells [1]. ACE2 levels are regulated through transcriptional, post-transcriptional, and post-translational means. For example, certain transcription factors enhance or reduce its transcription, and protein kinases and ubiquitination-related enzymes affect its protein levels [2]. ACE2 gene polymorphisms may be population-specific and could influence the severity of SARS-Cov-2 infection [3]. In addition, ACE2 is involved in glycolipid metabolism in multiple tissues, playing a role in Type 2 diabetes and related complications [4].

In conclusion, ACE2 is crucial for maintaining homeostasis, regulating glycolipid metabolism, and is a key player in the pathogenesis of COVID-19. Understanding the regulation of ACE2 through genetic and molecular mechanisms, as studied in various models, may help develop strategies for treating diseases related to ACE2 dysregulation, especially in the context of COVID-19 and metabolic diseases.

References:

1. Wang, Jieqiong, Zhao, Huiying, An, Youzhong. 2022. ACE2 Shedding and the Role in COVID-19. In Frontiers in cellular and infection microbiology, 11, 789180. doi:10.3389/fcimb.2021.789180. https://pubmed.ncbi.nlm.nih.gov/35096642/

2. Wang, Chia-Wen, Chuang, Huai-Chia, Tan, Tse-Hua. 2023. ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification. In Journal of biomedical science, 30, 71. doi:10.1186/s12929-023-00965-9. https://pubmed.ncbi.nlm.nih.gov/37608279/

3. Samtani, Ratika, Krishna, Kabir. . ACE2 and COVID-19: An anthropological perspective. In Anthropologischer Anzeiger; Bericht uber die biologisch-anthropologische Literatur, 78, 253-256. doi:10.1127/anthranz/2021/1327. https://pubmed.ncbi.nlm.nih.gov/33595589/

4. Li, Rui, Li, Fangyu, Yuan, Li. . ACE2 Regulates Glycolipid Metabolism in Multiple Tissues. In Frontiers in bioscience (Landmark edition), 29, 17. doi:10.31083/j.fbl2901017. https://pubmed.ncbi.nlm.nih.gov/38287822/