PMID- 36930656 OWN - NLM STAT- MEDLINE DCOM- 20230427 LR - 20230607 IS - 1522-1539 (Electronic) IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 324 IP - 6 DP - 2023 Jun 1 TI - High-plasma soluble prorenin receptor is associated with vascular damage in male, but not female, mice fed a high-fat diet. PG - H762-H775 LID - 10.1152/ajpheart.00638.2022 [doi] AB - Plasma soluble prorenin receptor (sPRR) displays sexual dimorphism and is higher in women with type 2 diabetes mellitus (T2DM). However, the contribution of plasma sPRR to the development of vascular complications in T2DM remains unclear. We investigated if plasma sPRR contributes to sex differences in the activation of the systemic renin-angiotensin-aldosterone system (RAAS) and vascular damage in a model of high-fat diet (HFD)-induced T2DM. Male and female C57BL/6J mice were fed either a normal fat diet (NFD) or an HFD for 28 wk to assess changes in blood pressure, cardiometabolic phenotype, plasma prorenin/renin, sPRR, and ANG II. After completing dietary protocols, tissues were collected from males to assess vascular reactivity and aortic reactive oxygen species (ROS). A cohort of male mice was used to determine the direct contribution of increased systemic sPRR by infusion. To investigate the role of ovarian hormones, ovariectomy (OVX) was performed at 32 wk in females fed either an NFD or HFD. Significant sex differences were found after 28 wk of HFD, where only males developed T2DM and increased plasma prorenin/renin, sPRR, and ANG II. T2DM in males was accompanied by nondipping hypertension, carotid artery stiffening, and aortic ROS. sPRR infusion in males induced vascular thickening instead of material stiffening caused by HFD-induced T2DM. While intact females were less prone to T2DM, OVX increased plasma prorenin/renin, sPRR, and systolic blood pressure. These data suggest that sPRR is a novel indicator of systemic RAAS activation and reflects the onset of vascular complications during T2DM regulated by sex.NEW & NOTEWORTHY High-fat diet (HFD) for 28 wk leads to type 2 diabetes mellitus (T2DM) phenotype, concomitant with increased plasma soluble prorenin receptor (sPRR), nondipping blood pressure, and vascular stiffness in male mice. HFD-fed female mice exhibiting a preserved cardiometabolic phenotype until ovariectomy revealed increased plasma sPRR and blood pressure. Plasma sPRR may indicate the status of systemic renin-angiotensin-aldosterone system (RAAS) activation and the onset of vascular complications during T2DM in a sex-dependent manner. FAU - Visniauskas, Bruna AU - Visniauskas B AUID- ORCID: 0000-0002-4525-2194 AD - Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana, United States. AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. AD - Tulane Center for Sex-Based Biology and Medicine, New Orleans, Louisiana, United States. FAU - Reverte, Virginia AU - Reverte V AUID- ORCID: 0000-0003-3225-6476 AD - Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Abshire, Caleb M AU - Abshire CM AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Ogola, Benard O AU - Ogola BO AUID- ORCID: 0000-0002-6084-6986 AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. AD - Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, United States. FAU - Rosales, Carla B AU - Rosales CB AD - Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Galeas-Pena, Michelle AU - Galeas-Pena M AUID- ORCID: 0000-0002-9257-3222 AD - Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Sure, Venkata N AU - Sure VN AUID- ORCID: 0000-0002-3657-962X AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Sakamuri, Siva S V P AU - Sakamuri SSVP AUID- ORCID: 0000-0003-3569-9985 AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Harris, Nicholas R AU - Harris NR AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Kilanowski-Doroh, Isabella AU - Kilanowski-Doroh I AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Mcnally, Alexandra B AU - Mcnally AB AUID- ORCID: 0000-0001-5516-4991 AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Horton, Alec C AU - Horton AC AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Zimmerman, Margaret AU - Zimmerman M AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Katakam, Prasad V G AU - Katakam PVG AUID- ORCID: 0000-0002-4708-9140 AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. FAU - Lindsey, Sarah H AU - Lindsey SH AUID- ORCID: 0000-0002-9837-4582 AD - Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, United States. AD - Tulane Center for Sex-Based Biology and Medicine, New Orleans, Louisiana, United States. AD - Tulane Hypertension and Renal Center of Excellence, New Orleans, Louisiana, United States. FAU - Prieto, Minolfa C AU - Prieto MC AUID- ORCID: 0000-0002-0199-3193 AD - Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana, United States. AD - Tulane Center for Sex-Based Biology and Medicine, New Orleans, Louisiana, United States. AD - Tulane Hypertension and Renal Center of Excellence, New Orleans, Louisiana, United States. LA - eng GR - R01 HL133619/HL/NHLBI NIH HHS/United States GR - K99 HL155841/HL/NHLBI NIH HHS/United States GR - R00 HL155841/HL/NHLBI NIH HHS/United States GR - P30 GM103337/GM/NIGMS NIH HHS/United States GR - R01 DK104375/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230317 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 RN - EC 3.4.23.15 (Renin) RN - 0 (Prorenin Receptor) RN - 0 (Reactive Oxygen Species) RN - 76634-96-3 (N-formyl-13-dihydrocarminomycin) RN - 0 (Receptors, Cell Surface) RN - EC 3.6.1.- (Vacuolar Proton-Translocating ATPases) SB - IM MH - Female MH - Male MH - Mice MH - Animals MH - Renin MH - Prorenin Receptor MH - *Diabetes Mellitus, Type 2 MH - Diet, High-Fat/adverse effects MH - Reactive Oxygen Species MH - Mice, Inbred C57BL MH - Renin-Angiotensin System/genetics MH - *Hypertension MH - Receptors, Cell Surface/genetics MH - Blood Pressure MH - *Vacuolar Proton-Translocating ATPases PMC - PMC10151046 OTO - NOTNLM OT - cardiovascular complications OT - circadian rhythms OT - reactive oxygen species OT - renin-angiotensin-aldosterone system OT - vascular dysfunction COIS- No conflicts of interest, financial or otherwise, are declared by the authors. EDAT- 2023/03/18 06:00 MHDA- 2023/04/27 06:42 PMCR- 2024/06/01 CRDT- 2023/03/17 13:43 PHST- 2024/06/01 00:00 [pmc-release] PHST- 2023/04/27 06:42 [medline] PHST- 2023/03/18 06:00 [pubmed] PHST- 2023/03/17 13:43 [entrez] AID - H-00638-2022 [pii] AID - 10.1152/ajpheart.00638.2022 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2023 Jun 1;324(6):H762-H775. doi: 10.1152/ajpheart.00638.2022. Epub 2023 Mar 17.