N-domain isoform of Angiotensin I converting enzyme as a marker of hypertension: populational study

Abstract

The aim of this paper was to investigate the presence of the urinary 90 kDa N-domain ACE in a cohort of the population from Vitoria, Brazil, to verify its association with essential hypertension since this isoform could be a possible genetic marker of hypertension. Anthropometric, clinical, and laboratory parameters of the individuals were evaluated (n = 1150) and the blood pressure (BP) was measured. The study population was divided according to ACE isoforms in urine as follows: ACE 65/90/190, presence of three ACE isoforms (n = 795), ACE 90(+) (65/90) (n = 186), and ACE 90(-) (65/190) (n = 169) based on the presence (+) or absence (-) of the 90 kDa ACE isoform. The anthropometric parameters, lipid profile, serum levels of uric acid, glucose, and the systolic and diastolic BP were significantly greater in the ACE 90(+) compared with the ACE 90(-) and ACE 65/90/190 individuals. We found that 98% of individuals from the ACE 90(+) group and 38% from the ACE 65/90/190 group had hypertension, compared to only 1% hypertensive individuals in the ACE 90(-) group. There is a high presence of the 90 kDa N-domain ACE isoform (85%) in the studied population. The percentile of normotensive subjects with three isoforms was 62%. Our findings could contribute to the development of new efficient strategy to prevent and treat hypertension to avoid the development of cardiovascular disease.

Figure 1

Chromatography of human urine from normal and hypertensive subjects on DEAE-cellulose. (a1) Normotensive subjects with two peaks with ACE activity corresponding to 190 and 65 kDa ACE; (b1) Hypertensive subjects with two peaks with ACE activity corresponding to 90 and 65 kDa ACE; (c1) Normotensive subjects with three peaks with ACE activity corresponding to 190, 90, and 65 kDa ACE. The dialyzed human urine (100 mL) was applied to a DEAE-cellulose column (1.5 × 10 cm). The column was washed with 20 mM Tris/HCl buffer, pH 7.0, and then eluted (fractions of 4.5 mL) with a linear gradient of 20 mM to 500 mM Tris/HCl buffer, pH 7.0, at a flow rate of 55 mL/h. (∘) Absorbance at 280 nm. (•) ACE activity with HHL as substrate. (□) Conductivity. Werstern blotting analysis of urinary ACEs. (a2) Normotensive subjects with 190 and 65 kDa ACE; (b2) Hypertensive subjects with 90 and 65 kDa ACE; (c2) Normotensive subjects with 190, 90, and 65 kDa ACE (as described in Section 2).

Figure 2

Distribution of ACE urinary isoforms and percentile of presence in subjects urine.

Figure 3

(a) Systolic and (b) diastolic blood pressure levels before (solid symbol) and after (open symbol) adjustment for age, gender, race, smoking status, diabetes incidence, antihypertensive use, BMI, waist-to-hip ratio, lipid profile, glucose, uric acid, and urinary sodium excretion. Values are mean ± SEM.