Viktor Bánhegyi1,2,3, Attila Enyedi4, Gábor Áron Fülöp1,2,5, Attila Oláh5, Ivetta Mányiné Siket1, Csongor Váradi4, Klaudia Bottyán1, Mária Lódi1, Alexandra Csongrádi1,2, Azeem J Umar1,2, Miklós Fagyas1,6, Dániel Czuriga6, István Édes6, Miklós Pólos5, Béla Merkely5, Zoltán Csanádi6, Zoltán Papp1,7, Gábor Szabó3, Tamás Radovits5, István Takács4, Attila Tóth1,7. 1. Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary. 2. Doctoral School of Kálmán Laki, University of Debrecen, 4032 Debrecen, Hungary. 3. Department of Cardiac Surgery, University of Halle, 06120 Halle (Saale), Germany. 4. Division of Thoracic Surgery, Department of Surgery, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary. 5. Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary. 6. Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary. 7. Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences-University of Debrecen, 4032 Debrecen, Hungary.
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.
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.
Authors: Aadil Yousif; Rashid Mir; Jamsheed Javid; Jameel Barnawi; Mohammed M Jalal; Malik A Altayar; Salem Owaid Albalawi; Faisel M Abuduhier Journal: Diagnostics (Basel) Date: 2022-05-26
Authors: Beáta Bódi; Patrick M Pilz; Lilla Mártha; Miriam Lang; Ouafa Hamza; Miklós Fagyas; Petra L Szabó; Dietmar Abraham; Attila Tóth; Bruno K Podesser; Attila Kiss; Zoltán Papp Journal: Int J Mol Sci Date: 2021-10-14 Impact factor: 5.923