Agtr1a-KO Mouse

Agtr1a, which encodes the angiotensin II type 1a receptor (AT1aR), is a key component of the renin-angiotensin system (RAS). The RAS is involved in cardiovascular control, hydromineral balance, and the neuroendocrine control of energy balance [1]. Angiotensin II acting on AT1aR within the central nervous system and periphery mediates actions related to regulating blood pressure and fluid intake to maintain cardiovascular and hydromineral homeostasis [2]. Genetic models, such as Agtr1a-knockout (KO) mice, are valuable tools for studying its function.

In Agtr1a -/- mice infused with aldosterone, there was no aortic and small artery remodeling, impaired endothelium-dependent relaxation, enhanced fibronectin and collagen deposition, or vascular inflammation, which were present in wild-type mice. This indicates that AGTR1a is required for mineralocorticoid receptor stimulation to induce vascular remodeling and inflammation and endothelial dysfunction [4]. In experimental autoimmune myocarditis, Agtr1a -/- mice showed reduced fibrosis and better systolic function at day 40 compared to wild-type mice, suggesting that Ang II-ATR1 signalling is critical for post-inflammatory fibrotic remodelling and dilated cardiomyopathy [5]. Proximal tubule-specific deletion of Agtr1a in PT-Agtr1a -/- mice attenuated circulating and intratubular angiotensin II-induced hypertension [3].

In conclusion, Agtr1a is essential for maintaining cardiovascular and hydromineral homeostasis through its role in the RAS. Studies using Agtr1a KO mouse models have revealed its significant contributions to vascular remodeling, endothelial function, cardiac fibrosis, and blood pressure regulation in disease conditions such as hypertension and post-inflammatory heart diseases [3,4,5].

References:

1. Paes-Leme, Bruno, Monteiro, Lívia da Rocha Natalino, Gholami, Khadijeh, Reis, Luis Carlos, Mecawi, André Souza. 2023. Fasting increases circulating angiotensin levels and brain Agtr1a expression in male rats. In Journal of neuroendocrinology, 35, e13334. doi:10.1111/jne.13334. https://pubmed.ncbi.nlm.nih.gov/37667574/

2. Baumer-Harrison, Caitlin, Patel, Sagar, Scott, Karen A, Krause, Eric G, de Kloet, Annette D. 2024. Optical perturbation of Agtr1a-containing neurons and afferents within the caudal nucleus of the solitary tract modulates sodium intake. In Physiology & behavior, 284, 114624. doi:10.1016/j.physbeh.2024.114624. https://pubmed.ncbi.nlm.nih.gov/38959991/

3. Li, Xiao Chun, Leite, Ana Paula Oliveira, Zheng, Xiaowen, Tauc, Michel, Zhuo, Jia Long. 2021. Proximal Tubule-Specific Deletion of Angiotensin II Type 1a Receptors in the Kidney Attenuates Circulating and Intratubular Angiotensin II-Induced Hypertension in PT-Agtr1a-/- Mice. In Hypertension (Dallas, Tex. : 1979), 77, 1285-1298. doi:10.1161/HYPERTENSIONAHA.120.16336. https://pubmed.ncbi.nlm.nih.gov/33641366/

4. Briet, Marie, Barhoumi, Tlili, Mian, Muhammad Oneeb Rehman, Paradis, Pierre, Schiffrin, Ernesto L. 2016. Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors. In Hypertension (Dallas, Tex. : 1979), 67, 897-905. doi:10.1161/HYPERTENSIONAHA.115.07074. https://pubmed.ncbi.nlm.nih.gov/27045029/

5. Czepiel, Marcin, Diviani, Dario, Jaźwa-Kusior, Agnieszka, Kania, Gabriela, Błyszczuk, Przemysław. . Angiotensin II receptor 1 controls profibrotic Wnt/β-catenin signalling in experimental autoimmune myocarditis. In Cardiovascular research, 118, 573-584. doi:10.1093/cvr/cvab039. https://pubmed.ncbi.nlm.nih.gov/33576779/