Agtrap, also known as Angiotensin II Receptor-Associated Protein (ATRAP), is a molecule that specifically interacts with the carboxyl-terminal domain of the Ang II type 1 receptor (AT1R) [1]. It has been shown to suppress Ang II-mediated pathological responses in cardiovascular cells by promoting AT1R internalization. Agtrap is broadly expressed in many tissues, similar to AT1R, and a tissue-specific regulatory balance of Agtrap and AT1R expression may be involved in modulating AT1R signaling at local tissue sites, as well as in the pathophysiology of hypertension and its associated end-organ injury [1].

In mouse models, Agtrap-deficient (Agtrap-/-) mice displayed systemic metabolic dysfunction under dietary high-fat loading, including increased pad fat accumulation, hypertension, dyslipidemia, and insulin resistance, along with adipose tissue inflammation, indicating that Agtrap plays a protective role against insulin resistance [2]. In prehypertensive losartan-treated spontaneously hypertensive rats (SHRs), hypomethylation of Agtrap accompanied by upregulation of ATRAP expression in the myocardium was associated with long-term inhibition of left ventricular hypertrophy (LVH) [3].

In conclusion, Agtrap is crucial in regulating AT1R-mediated responses and has protective functions against metabolic disorders and LVH. The study of Agtrap knockout mouse models has provided valuable insights into its role in metabolic and cardiovascular diseases, helping to understand the underlying mechanisms and potentially guiding the development of new therapeutic strategies for these diseases [2,3].

References:

1. Tamura, Kouichi, Wakui, Hiromichi, Maeda, Akinobu, Yamashita, Akio, Umemura, Satoshi. . The physiology and pathophysiology of a novel angiotensin receptor-binding protein ATRAP/Agtrap. In Current pharmaceutical design, 19, 3043-8. doi:. https://pubmed.ncbi.nlm.nih.gov/23176217/

2. Maeda, Akinobu, Tamura, Kouichi, Wakui, Hiromichi, Toya, Yoshiyuki, Umemura, Satoshi. 2013. Angiotensin receptor-binding protein ATRAP/Agtrap inhibits metabolic dysfunction with visceral obesity. In Journal of the American Heart Association, 2, e000312. doi:10.1161/JAHA.113.000312. https://pubmed.ncbi.nlm.nih.gov/23902639/

3. Wang, Ting-Jun, Lian, Gui-Li, Lin, Xu, Wang, Hua-Jun, Xie, Liang-Di. 2016. Hypomethylation of Agtrap is associated with long-term inhibition of left ventricular hypertrophy in prehypertensive losartan-treated spontaneously hypertensive rats. In Molecular medicine reports, 15, 839-846. doi:10.3892/mmr.2016.6040. https://pubmed.ncbi.nlm.nih.gov/28000857/