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• W3020008982 abstract "Background Ang-(1-12) is a primary non-renin dependent substrate for direct tissue angiotensin II (Ang II) formation by chymase. This discovery challenges conventional thinking and explains the large residual risk of cardiovascular events in patients medicated with blockers of the renin angiotensin system (RAS). Here we report the first demonstration of circulating Ang-(1-12) as a biomarker of essential hypertension (EH) and cardio-renal remodeling. Methods The cohort of patients from Olmsted County MN included 52 healthy adult volunteers (21 females), age 54 ± 8 years, and 23 essential hypertensive (EH) patients (14 females) age 61 ± 8 years with systolic blood pressure (SBP) ≥140 mm Hg prior to recruitment. Clinical examination, standardized BP measurements, and venous blood were obtained for measurements of plasma concentrations of angiotensinogen (AGT), Ang-(1-12), Ang II, aldosterone, renin activity, N-terminal pro–B-type natriuretic peptide (NT-proBNP) and atrial and brain natriuretic peptides (ANP and BNP, respectively). All values are Means ± SD. Data were analyzed by 2-way ANOVA for sex and hypertension. Results Plasma Ang-(1-12) levels in EHs [SBP: 134 ± 14 mm Hg; Ang-(1-12): 1,463 ± 446] were higher than normotensives [SBP: 117 ± 13 mm Hg; Ang-(1-12): 1,353 ± 379 fmol/mL, hypertension effect: P<0.05], irrespective of sex. Hypertension associated with increases in pulse pressure, PRA, and plasma AGT and NT-proBNP concentrations (see Figure 1). The elevation in circulating NT-proBNP levels with hypertension was accounted for by a 4.6-fold increase in hypertensive males (165 ± 134 pg/mL) while the 1.5-fold rise in plasm NT-proBNP did reach significance (134 ± 127 pg/mL, p> 0.05). Conclusions We show for the first time that Ang-(1-12) circulates in humans and its concentrations are elevated by chronic hypertension. We further demonstrate a sexual dimorphic pattern in hypertensives with respect to NT-proBNP, the latter a biomarker for cardiac remodeling. Whether this represents a natriuretic system-related compensatory mechanism, or worsening pathology, due to an elevated noncanonical RAS specific to male hypertensives remains to be studied. Further investigation to fully define the role of Ang-(1-12) as a cardiac disease biomarker in a larger, gender and ethnic diverse population and its relationship to hypertension and myocardial structure is warranted. Support or Funding Information Supported by grant HL-051952 from the NHLBI of the NIH Figure 1Open in figure viewerPowerPoint Lines are means ± SD" @default.
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• W3020008982 date "2020-04-01" @default.
• W3020008982 modified "2023-09-24" @default.
• W3020008982 title "Human Angiotensin‐(1‐12) [Ang‐(1‐12)] is a Hypertension and Cardiac Disease Biomarker" @default.
• W3020008982 doi "https://doi.org/10.1096/fasebj.2020.34.s1.09150" @default.
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