Human Tissue Angiotensin Converting Enzyme (ACE) Activity Is Regulated by Genetic Polymorphisms, Posttranslational Modifications, Endogenous Inhibitors and Secretion in the Serum, Lungs and Heart.
Cells
; 10(7)2021 07 06.
مقالة
ي الانجليزية
| MEDLINE | ID: covidwho-1302160
ABSTRACT
Objective:
Inhibitors of the angiotensin converting enzyme (ACE) are the primarily chosen drugs to treat heart failure and hypertension. Moreover, an imbalance in tissue ACE/ACE2 activity is implicated in COVID-19. In the present study, we tested the relationships between circulating and tissue (lung and heart) ACE levels in men.Methods:
Serum, lung (n = 91) and heart (n = 72) tissue samples were collected from Caucasian patients undergoing lung surgery or heart transplantation. ACE I/D genotype, ACE concentration and ACE activity were determined from serum and tissue samples. Clinical parameters were also recorded.Results:
A protocol for ACE extraction was developed for tissue ACE measurements. Extraction of tissue-localized ACE was optimal in a 0.3% Triton-X-100 containing buffer, resulting in 260 ± 12% higher ACE activity over detergent-free conditions. SDS or higher Triton-X-100 concentrations inhibited the ACE activity. Serum ACE concentration correlated with ACE I/D genotype (II 166 ± 143 ng/mL, n = 19, ID 198 ± 113 ng/mL, n = 44 and DD 258 ± 109 ng/mL, n = 28, p < 0.05) as expected. In contrast, ACE expression levels in the lung tissue were approximately the same irrespective of the ACE I/D genotype (II 1423 ± 1276 ng/mg, ID 1040 ± 712 ng/mg and DD 930 ± 1273 ng/mg, p > 0.05) in the same patients (values are in median ± IQR). Moreover, no correlations were found between circulating and lung tissue ACE concentrations and activities (Spearman's p > 0.05). In contrast, a significant correlation was identified between ACE activities in serum and heart tissues (Spearman's Rho = 0.32, p < 0.01). Finally, ACE activities in lung and the serum were endogenously inhibited to similar degrees (i.e., to 69 ± 1% and 53 ± 2%, respectively).Conclusion:
Our data suggest that circulating ACE activity correlates with left ventricular ACE, but not with lung ACE in human. More specifically, ACE activity is tightly coordinated by genotype-dependent expression, endogenous inhibition and secretion mechanisms.الكلمات الدالة
النص الكامل:
متاح
مجموعة:
قواعد البيانات الدولية
قاعدة البيانات:
MEDLINE
الموضوع الرئيسي:
Peptidyl-Dipeptidase A
نوع الدراسة:
دراسة النذير
المحددات:
كبير في السن
/
أنثى
/
البشر
/
ذكر
/
منتصف العمر
اللغة:
الانجليزية
السنة:
2021
نوع:
مقالة
بلد الانتماء:
Cells10071708
المراجع ذات الصلة
MEDLINE
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