Ace-KO Mouse

Ace, short for Angiotensin-converting enzyme, is a zinc-dependent dipeptidyl carboxypeptidase. It is a key component of the renin-angiotensin-aldosterone system (RAAS), which is crucial for blood pressure homeostasis. ACE generates the vasoconstrictor peptide angiotensin II, thus regulating blood pressure [4]. It also plays roles in immune regulation, with intrinsic ACE detected in immune cell populations like macrophages and neutrophils [3].

ACE inhibitors, which target the Ace gene product, are widely used drugs. A common adverse effect is a dry cough, occurring in around 10% of patients, likely due to suppression of kininase II activity and subsequent accumulation of kinins, substance P, and prostaglandins [1]. In the context of COVID-19, the related protein ACE2 is a central actor, as it serves as the receptor for the virus and its relative deficiency during infection may contribute to clinical features [2]. Also, ACE phenotyping shows potential in detecting diseases. In lung and prostate cancer, ACE activity and its conformational fingerprint change, which may help in early diagnosis [5,6]. In extrapulmonary sarcoidosis, ACE phenotyping can non-invasively identify patients with the disease [7].

In conclusion, Ace is essential for maintaining blood pressure through its role in the RAAS and also impacts immune regulation. Studies on Ace-related processes, such as the effects of ACE inhibitors and ACE phenotyping in various diseases like COVID-19, cancer, and sarcoidosis, contribute to understanding disease mechanisms and developing diagnostic and treatment strategies.

References:

1. Overlack, A. . ACE inhibitor-induced cough and bronchospasm. Incidence, mechanisms and management. In Drug safety, 15, 72-8. doi:. https://pubmed.ncbi.nlm.nih.gov/8862965/

2. Cousin, Vladimir L, Giraud, Raphael, Bendjelid, Karim. 2021. Pathophysiology of COVID-19: Everywhere You Look You Will See ACE2! In Frontiers in medicine, 8, 694029. doi:10.3389/fmed.2021.694029. https://pubmed.ncbi.nlm.nih.gov/34513868/

3. Oosthuizen, Delia, Sturrock, Edward D. 2022. Exploring the Impact of ACE Inhibition in Immunity and Disease. In Journal of the renin-angiotensin-aldosterone system : JRAAS, 2022, 9028969. doi:10.1155/2022/9028969. https://pubmed.ncbi.nlm.nih.gov/36016727/

4. Rahimi, Zohreh. 2012. ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy. In Journal of nephropathology, 1, 143-51. doi:10.5812/nephropathol.8109. https://pubmed.ncbi.nlm.nih.gov/24475405/

5. Danilov, Sergei M, Metzger, Roman, Klieser, Eckhard, Trakht, Ilya N, Garcia, Joe G N. 2019. Tissue ACE phenotyping in lung cancer. In PloS one, 14, e0226553. doi:10.1371/journal.pone.0226553. https://pubmed.ncbi.nlm.nih.gov/31877149/

6. Danilov, Sergei M, Kadrev, Alexey V, Kurilova, Olga V, Samokhodskaya, Larisa M, Kamalov, Armais A. 2019. Tissue ACE phenotyping in prostate cancer. In Oncotarget, 10, 6349-6361. doi:10.18632/oncotarget.27276. https://pubmed.ncbi.nlm.nih.gov/31695843/

7. Danilov, Sergei M, Kurilova, Olga V, Sinitsyn, Valentin E, Garcia, Joe G N, Dudek, Steven M. 2022. Predictive potential of ACE phenotyping in extrapulmonary sarcoidosis. In Respiratory research, 23, 211. doi:10.1186/s12931-022-02145-z. https://pubmed.ncbi.nlm.nih.gov/35996109/