Sex differences in the aging pattern of renin\u2013angiotensin system serum peptidases

A Fernández-Atucha,M Kortajarena,A Izagirre,P Martinez-Lage,J Gil,E Echevarría,A B Fraile-Bermúdez,G Larrinaga

doi:10.1186/s13293-017-0128-8

Abstract

BackgroundSerum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin–angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants.MethodsOne hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL).ResultsSignificantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (<55 years) men had significantly higher values of NEP serum activity than younger women. Significantly lower ACE serum activity was detected in older men compared to younger men. In women, significantly higher ACE2 serum activity was observed in older women compared to younger women.ConclusionsThese results suggest a differential effect of aging on the activity of RAS enzymes in men and women, especially with respect to the breakpoint of andropausia/menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.

Highlights

Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin–angiotensin system (RAS)
All samples were analyzed in triplicate and incubated at 37 ° C with their respective fluorogenic substrates in microplates for either 30 min (ACE, APA, APN, NEP/CD10) or 2 h (ACE2)
A lack of changes in these parameters was observed in men when comparing the under 55 group to those over 55 years and in women over 55, presented a tendency toward higher systolic blood pressure (P = 0.078) compared to women under 55 years (Table 3)

Summary

Introduction

Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin–angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. The imbalance of RAS components has been associated with several chronic pathologies that go beyond cardiovascular and renal diseases [6], including proliferative (such as cancer) [7, 8] and degenerative disorders of the central nervous system (such as Alzheimer’s disease) [9, 10] These diseases are primarily responsible for morbidity and mortality of adults in Western countries [11,12,13].

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