New insights into the importance of aminopeptidase A in hypertension

Abstract

The renin-angiotensin system (RAS) plays an important role in the maintenance of normal blood pressure and the etiology of hypertension; however, minimal attention has been paid to the degradation of the effector peptide, angiotensin II (AngII). Since aminopeptidase A (APA)-deficient mice develop hypertension APA appears to be an essential enzyme in the control of blood pressure via degradation of AngII. The robust hypertension seen in the spontaneously hypertensive rat (SHR) is due to activation of the RAS, and an accompanying decrease in kidney APA. Changes in APA have also been measured during the activation of the RAS in the Goldblatt hypertension model and Dahl salt-sensitive (DSS) rat. The DSS rat shows an elevation in renal APA activity at the onset of hypertension suggesting a protective role against elevations in circulating AngII, followed by decreased APA activity with advancing hypertension. Changes seen in human maternal serum APA activity during preeclampsia are similar to changes measured in renal APA in the DSS rat model. APA activity is higher than during normal pregnancy at the onset of preeclampsia, and with advancing preeclampsia (severe preeclampsia) declines below that seen during normal pregnancy. Serum APA activity is also increased during hormone replacement therapy (HRT), perhaps in reaction to elevated levels of AngII. Thus, it appears important to consider the relationship among activation of the RAS, circulating levels of AngII, and the availability of APA in hypertensive disorders.

Transcriptome Analysis of K-877 (a Novel Selective PPARα Modulator (SPPARMα))-Regulated Genes in Primary Human Hepatocytes and the Mouse Liver

“…These include mannose-binding lectin 2 (MBL2) 49,50) and glutamyl aminopeptidase ENPEP 51,52) . MBL is an important protein of the humoral innate immune system, and it has been reported that the serum MBL concentrations are decreased in obese subjects, accompanied by an increase in inflammatory markers 49) .…”

“…In addition, G54D MBL2 gene polymorphisms confer an increased risk for developing gestational diabetes mellitus 50) . ENPEP is an enzyme that facilitates the conversion of angiotensin , the main effector protein of the renin-angiotensin-aldosterone system, to angiotensin 51) . In addition, Enpep KO mice develop hypertension, and recombinant ENPEP treatment significantly decreases systolic blood pressure 52) , suggesting that ENPEP is an essential enzyme for controlling blood pressure.…”

Activity of soluble aminopeptidase A and dipeptidyl peptidase IV and membrane-bound aminopeptidase B and pyroglutamyl peptidase I in adenoid hyperplasia, tonsillar hyperplasia and chronic tonsillitis

“…This ectoenzyme, also known as glutamyl aminopeptidase (EC 3.4.11.7), has also been described in cytosolic fractions and body fluids [23,24]. Previous studies have indicated the involvement of APA in immune response as this enzyme is expressed in developing B lymphocytes and regulated by interleukins [25].…”

Qiliqiangxin Improves Cardiac Function in Spontaneously Hypertensive Rats Through the Inhibition of Cardiac Chymase

“…1 The development of cardiac fibrosis and subsequent diastolic and systolic dysfunction is a major complication of hypertensive heart disease. It contributes to the progressive disruption of the normal cardiac structure, which results in an increased risk of adverse cardiac events, such as myocardial ischemia, infarction, arrhythmias and sudden cardiac death.…”