Human Tissue Angiotensin Converting Enzyme (ACE) Activity Is Regulated by Genetic
Polymorphisms, Posttranslational Modifications, Endogenous Inhibitors and Secretion
in the Serum, Lungs and Heart
PEPSYS-A peptiderg szignalizáció komplexitása és szerepe szisztémás betegségekben(GINOP-2.3.2-15-2016-00050)
Támogató: NKFIH
A szívelégtelenség kezelésében használt Omecamtiv Mecarbil hatásainak feltérképezése
és a potenci...(ÚNKP-18–3-III-DE-209) Támogató: ITM
Szív- és érkutatási kiválóságközpont (IRONHEART)(GINOP-2.3.2-15-2016-00043) Támogató:
GINOP
Tématerületi Kiválósági Program 2019(ED-18-1-2019-0028) Támogató: ITM
Big Data, Biotechnológia, Energetika, Terápiás célú fejlesztés, Vízzel kapcsolatos
kutatások és a...(TKP2020-IKA-04) Támogató: ITM
(TKP2020-NKA-04)
Thematic Excellence Program (Semmelweis University)(2020-4.1.1.-TKP2020) Támogató:
Innovációs és Technológiai Minisztérium
Nemzeti szívprogram(NVKP_16-1–2016-0017) Támogató: NKFIH
Angiotenzin konvertáló enzim endogén szabályozása poszttranszlációs módosításokkal
és ennek szere...(FK 128809) Támogató: NKFIH
A szívelégtelenség kialakulásának és új kezelési lehetőségeinek experimentális vizsgálata(K
134939) Támogató: NKFIH
Kezelés-specifikus diagnosztikus módszerek fejlesztése a személyre szabott kardiovaszkuláris
terá...(K 132623)
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.
