Circulating ACE2 activity correlates with cardiovascular disease development.

Katalin Úri,Attila Borbély,Csaba Jenei,Attila Tóth,Miklós Fagyas,Erzsébet Lizanecz,István Édes,Attila Kertész,Zoltán Papp,Orsolya Bene,Zoltán Csanádi,Walter J Paulus

doi:10.1177/1470320316668435

Abstract

It was shown recently that angiotensin-converting enzyme activity is limited by endogenous inhibition in vivo, highlighting the importance of angiotensin II (ACE2) elimination. The potential contribution of the ACE2 to cardiovascular disease progression was addressed. Serum ACE2 activities were measured in different clinical states (healthy, n=45; hypertensive, n=239; heart failure (HF) with reduced ejection fraction (HFrEF) n=141 and HF with preserved ejection fraction (HFpEF) n=47). ACE2 activity was significantly higher in hypertensive patients (24.8±0.8 U/ml) than that in healthy volunteers (16.2±0.8 U/ml, p=0.01). ACE2 activity further increased in HFrEF patients (43.9±2.1 U/ml, p=0.001) but not in HFpEF patients (24.6±1.9 U/ml) when compared with hypertensive patients. Serum ACE2 activity negatively correlated with left ventricular systolic function in HFrEF, but not in hypertensive, HFpEF or healthy populations. Serum ACE2 activity had a fair diagnostic value to differentiate HFpEF from HFrEF patients in this study. Serum ACE2 activity correlates with cardiovascular disease development: it increases when hypertension develops and further increases when the cardiovascular disease further progresses to systolic dysfunction, suggesting that ACE2 metabolism plays a role in these processes. In contrast, serum ACE2 activity does not change when hypertension progresses to HFpEF, suggesting a different pathomechanism for HFpEF, and proposing a biomarker-based identification of these HF forms.

Highlights

The cardiovascular continuum was first proposed by Dzau and Braunwald, giving a mechanistic view of the pathomechanism of heart failure (HF).[1]
These may progress to HF, which has two distinct forms: heart failure with reduced ejection fraction (HFrEF) is characterized by systolic dysfunction, while HF with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction.[13]
The most important finding was that serum angiotensin-converting enzyme 2 (ACE2) activity does not change upon progression of hypertension to HFpEF, contrasting with progression of hypertension to HFrEF

Summary

Introduction

The cardiovascular continuum was first proposed by Dzau and Braunwald, giving a mechanistic view of the pathomechanism of heart failure (HF).[1] Our current view of the cardiovascular continuum suggests that the steps of cardiovascular disease development are risk factors (including hypertension), vascular disease, tissue injury, pathological remodeling, target organ dysfunction, organ failure and death. In spite of much effort, the pathophysiological mechanism of the disease is still not identified in many cases. There is no known cause of hypertension in the majority of cases (primary or essential hypertension),[2] and the exact molecular mechanisms of disease progression are unidentified. Cardiovascular disease is still the leading cause of death in developed countries.[3] The initial steps of preclinical cardiovascular disease are hypertension, dyslipidemia and diabetes.[1] These underlying pathologies are all hazards for developing advanced coronary atherosclerosis and myocardial infarction. Despite aggressive coronary revascularization strategies, some patients with coronary heart disease display

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Conclusion