ACE2 activity is increased in monocyte-derived macrophages from prehypertensive subjects.
BACKGROUND
Hypertension is a major risk factor for cardiovascular disease and the renin-angiotensin-aldosterone system (RAAS) plays a central pathophysiological role in its formation. Angiotensin-converting enzyme (ACE) and its homologue ACE2 control the formation of counteracting effectors, angiotensin II (AngII), a potent vasopressor and Ang-(1-7) which has vasodilatory action. It is therefore hypothesized that the balance of the activities of these two enzymes, ACE and ACE2, could be important for the control of blood pressure (BP).


METHODS
Monocyte-derived macrophages were isolated from blood samples of normotensives (NT), prehypertensives (preHTN) and untreated hypertensive (HTN) male patients (n = 28, 18 and 11, respectively). The activities of ACE2 were determined by measuring leucine or phenylalanine released following hydrolysis of Ang I and Ang II, respectively. The activity of ACE was measured using a synthetic substrate.


RESULTS
The levels of BP were 112.6 +/- 1.4/74.8 +/- 1.2, 128.3 +/- 0.8/78.1 +/- 1.2 and 151.4 +/- 2.7/99.3 +/- 2.4 mmHg in the NT, preHTN and HTN, respectively (P < 0.001). The ACE2-mediated Ang II degrading activity (ACE2-II) was 1201 +/- 241 fmol/min/mg cell protein in NT subjects and was significantly (P < 0.01) increased by 2.4-fold in preHTN. ACE2-II activity in HTN and NT was not significantly different. ACE2-mediated Ang I hydrolysis (ACE2-I) was 85-fold lower than the ACE2-II activity. ACE activity in the human monocyte-derived macrophages (HMDM) averaged 21.6 +/- 3.0 mU/mg cell protein and did not differ among the three groups.


CONCLUSIONS
PreHTN subjects have higher ACE2-II activity compared with HTN subjects, suggesting a protective role for ACE2 in the early stage of HTN development, probably by accelerated degradation of the vasopressor AngII.
Keidar
Shlomo
S
Bruce Rappaport Faculty of Medicine, and Internal Medicine Department A, Rambam Medical Center, 31096 Haifa, Israel. skeidar@rambam.health.gov.il
Strizevsky
Alexander
A
Raz
Ayelet
A
Gamliel-Lazarovich
Aviva
A
D000328:Adult; D000085962:Angiotensin-Converting Enzyme 2; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood*
D015415:Biomarkers; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2