ArticleClinical science (London, England : 1979)2021
Soluble (pro)renin receptor induces endothelial dysfunction and hypertension in mice with diet-induced obesity via activation of angiotensin II type 1 receptor.
Article in Clinical science (London, England : 1979), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 49 citations in OpenAlex.
- ELABELA Ameliorates Atherosclerosis Through Restoring the M1/M2 Macrophage Balance inJournal of the American Heart Association · 2025Article
- From fat to filter: the effect of adipose tissue-derived signals on kidney function.Nature reviews. Nephrology · 2025Review
- Importance of the (Pro)renin Receptor in Activating the Renin-Angiotensin System During Normotensive and Preeclamptic Pregnancies.Current hypertension reports · 2024Review
- Obesity Human Soluble Prorenin Receptor Expressed in Adipose Tissue Improves Insulin Sensitivity and Endothelial Function in Obese Female Mice.bioRxiv : the preprint server for biology · 2024Article
- Targeting the High-Density Lipoprotein Proteome for the Treatment of Post-Acute Sequelae of SARS-CoV-2.International journal of molecular sciences · 2024Article
- Human soluble prorenin receptor expressed in mouse renal collecting duct shows sex-specific effect on cardiorenal function.American journal of physiology. Renal physiology · 2024Article
- Assessment of the (Pro)renin Receptor Protein Expression in Organs.Current issues in molecular biology · 2024Article
- High-plasma soluble prorenin receptor is associated with vascular damage in male, but not female, mice fed a high-fat diet.American journal of physiology. Heart and circulatory physiology · 2023Article
- Soluble (Pro)Renin Receptor in Hypertension.Nephron · 2023Review
- The role of (pro)renin receptor and its soluble form in cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Therapeutic potential ofFrontiers in pharmacology · 2023Article
- Potential of soluble (pro)renin receptor in kidney disease: can it go beyond a biomarker?American journal of physiology. Renal physiology · 2022Review
- Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.Pharmacological reviews · 2022Review
- Soluble (Pro)renin Receptor Is Adversely Associated with Indices of Left Ventricular Structure and Function: The African-PREDICT Study.Journal of cardiovascular development and disease · 2022Article
- Inhibitory effect of (pro)renin receptor decoy inhibitor PRO20 on endoplasmic reticulum stress during cardiac remodeling.Frontiers in pharmacology · 2022Article
- Soluble (Pro)Renin Receptor as a Negative Regulator of NCC (NaHypertension (Dallas, Tex. : 1979) · 2021Article
- Adipose Tissue-Endothelial Cell Interactions in Obesity-Induced Endothelial Dysfunction.Frontiers in cardiovascular medicine · 2021Review
- Advanced Oxidation Protein Product Promotes Oxidative Accentuation in Renal Epithelial Cells via the Soluble (Pro)renin Receptor-Mediated Intrarenal Renin-Angiotensin System and Nox4-HOxidative medicine and cellular longevity · 2021Article
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11 authors at 2 institutions in 2 countries.
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Abstract
Until now, renin-angiotensin system (RAS) hyperactivity was largely thought to result from angiotensin II (Ang II)-dependent stimulation of the Ang II type 1 receptor (AT1R). Here we assessed the role of soluble (pro)renin receptor (sPRR), a product of site-1 protease-mediated cleavage of (pro)renin receptor (PRR), as a possible ligand of the AT1R in mediating: (i) endothelial cell dysfunction in vitro and (ii) arterial dysfunction in mice with diet-induced obesity. Primary human umbilical vein endothelial cells (HUVECs) treated with a recombinant histidine-tagged sPRR (sPRR-His) exhibited IκBα degradation concurrent with NF-κB p65 activation. These responses were secondary to sPRR-His evoked elevations in Nox4-derived H2O2 production that resulted in inflammation, apoptosis and reduced NO production. Each of these sPRR-His-evoked responses was attenuated by AT1R inhibition using Losartan (Los) but not ACE inhibition using captopril (Cap). Further mechanistic exploration revealed that sPRR-His activated AT1R downstream Gq signaling pathway. Immunoprecipitation coupled with autoradiography experiments and radioactive ligand competitive binding assays indicate sPRR directly interacts with AT1R via Lysine199 and Asparagine295. Important translational relevance was provided by findings from obese C57/BL6 mice that sPRR-His evoked endothelial dysfunction was sensitive to Los. Besides, sPRR-His elevated blood pressure in obese C57/BL6 mice, an effect that was reversed by concurrent treatment with Los but not Cap. Collectively, we provide solid evidence that the AT1R mediates the functions of sPRR during obesity-related hypertension. Inhibiting sPRR signaling should be considered further as a potential therapeutic intervention in the treatment and prevention of cardiovascular disorders involving elevated blood pressure.
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