Circulating angiotensin converting enzyme 2 activity as a biomarker of silent atherosclerosis in patients with chronic kidney disease

Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José M.; Barrios, Clara; Betriu, Àngels; Clotet, Sergi; Mojal, Sergi; Fernàndez, Elvira; Soler, María José

doi:10.1016/j.atherosclerosis.2016.08.032

Cited by 34 publications

(38 citation statements)

References 43 publications

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“…ACE2 enzymatic activity was already previously established and validated in our laboratory by using a specific ACE2 quenched fluorogenic substrate [25,26,27]. The optimal amount of each studied tissue was determined by reactions with increasing amounts of protein in pulmonary, cardiac, hepatic, and pancreatic tissues of both CONT and DB samples (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

Roca-Ho

Riera

Palau

et al. 2017

IJMS

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Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS.

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Section: Resultsmentioning

confidence: 99%

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

Roca-Ho

Riera

Palau

et al. 2017

IJMS

Self Cite

258

212

View full text Add to dashboard Cite

show abstract

“…Out of those, 481 had available plasma samples to measure FGF-2 levels. Samples from the other patients had already been spent to measure other biomarkers in sub-studies within the NEFRONA study (22,23). In any case, both populations did not differ in most of the parameters of the study, although there was a lower proportion of patients in dialysis than in the total sample.…”

Section: Design and Study Populationmentioning

confidence: 99%

Association of FGF-2 Concentrations with Atheroma Progression in Chronic Kidney Disease Patients

Božić

Betriu

Bermúdez-López

et al. 2018

CJASN

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“…[ 6 ] In human myocardium, ACE2 is localized to the endothelium of the microcirculation,[ 7 ] and is also present in the media of atherosclerotic radial arteries. [ 8 ] In healthy individuals, circulating ACE2 activity levels are low[ 9 , 10 ] but increase in the presence of CV disease or risk factors including heart failure (HF),[ 11 ] atrial fibrillation (AF),[ 12 ] kidney disease[ 13 , 14 ] and type 1 diabetes. [ 15 ] To date, there is limited information on the prognostic role of circulating ACE2 activity levels and the results are conflicting.…”

Section: Introductionmentioning

confidence: 99%

Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease

et al. 2018

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BackgroundAngiotensin converting enzyme 2 (ACE2) is an endogenous regulator of the renin angiotensin system. Increased circulating ACE2 predicts adverse outcomes in patients with heart failure (HF), but it is unknown if elevated plasma ACE2 activity predicts major adverse cardiovascular events (MACE) in patients with obstructive coronary artery disease (CAD).MethodsWe prospectively recruited patients with obstructive CAD (defined as ≥50% stenosis of the left main coronary artery and/or ≥70% stenosis in ≥ 1 other major epicardial vessel on invasive coronary angiography) and measured plasma ACE2 activity. Patients were followed up to determine if circulating ACE2 activity levels predicted the primary endpoint of MACE (cardiovascular mortality, HF or myocardial infarction).ResultsWe recruited 79 patients with obstructive coronary artery disease. The median (IQR) plasma ACE2 activity was 29.3 pmol/ml/min [21.2–41.2]. Over a median follow up of 10.5 years [9.6–10.8years], MACE occurred in 46% of patients (36 events). On Kaplan-Meier analysis, above-median plasma ACE2 activity was associated with MACE (log-rank test, p = 0.035) and HF hospitalisation (p = 0.01). After Cox multivariable adjustment, log ACE2 activity remained an independent predictor of MACE (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.24–4.72, p = 0.009) and HF hospitalisation (HR: 4.03, 95% CI: 1.42–11.5, p = 0.009).ConclusionsPlasma ACE2 activity independently increased the hazard of adverse long-term cardiovascular outcomes in patients with obstructive CAD.

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Circulating angiotensin converting enzyme 2 activity as a biomarker of silent atherosclerosis in patients with chronic kidney disease

Abstract: In CKD3-5 patients, higher circulating ACE2 activity at baseline is associated with higher risk for silent atherosclerosis, suggesting that ACE2 may serve as a biomarker to predict CV risk before CVD is established.

Cited by 34 publications

References 43 publications

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

Association of FGF-2 Concentrations with Atheroma Progression in Chronic Kidney Disease Patients

Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease

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