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.

Transient receptor potential melastatin-4 (TRPM4) is activated by an increase in intracellular Ca²⁺ concentration and is expressed on smooth muscle cells (SMCs). It is implicated in the myogenic constriction of cerebral arteries. We hypothesized that TRPM4 has a general role in intracellular Ca²⁺ signal amplification in a wide range of blood vessels. TRPM4 function was tested with the TRPM4 antagonist 9-phenanthrol and the TRPM4 activator A23187 on the cardiovascular responses of the rat, in vivo and in isolated basilar, mesenteric, and skeletal muscle arteries. TRPM4 inhibition by 9-phenanthrol resulted in hypotension and a decreased heart rate in the rat. TRPM4 inhibition completely antagonized myogenic tone development and norepinephrine-evoked vasoconstriction, and depolarization (high extracellular KCl concentration) evoked vasoconstriction in a wide range of peripheral arteries. Vasorelaxation caused by TRPM4 inhibition was accompanied by a significant decrease in intracellular Ca²⁺ concentration, suggesting an inhibition of Ca²⁺ signal amplification. Immunohistochemistry confirmed TRPM4 expression in the smooth muscle cells of the peripheral arteries. Finally, TRPM4 activation by the Ca²⁺ ionophore A23187 was competitively inhibited by 9-phenanthrol. In summary, TRPM4 was identified as an essential Ca²⁺-amplifying channel in peripheral arteries, contributing to both myogenic tone and agonist responses. These results suggest an important role for TRPM4 in the circulation. The modulation of TRPM4 activity may be a therapeutic target for hypertension. Furthermore, the Ca²⁺ ionophore A23187 was identified as the first high-affinity (nanomolar) direct activator of TRPM4, acting on the 9-phenanthrol binding site.

Although radial access is the current gold standard for the implementation of percutaneous coronary interventions (PCI), post-procedural radial compression devices are seldom compared with each other in terms of safety or efficacy. Our group aimed to compare a cost effective and potentially green method to dedicated radial compression devices, with respect to access site complications combined in a device oriented complex endpoint (DOCE), freedom from which served as our primary endpoint. Patients undergoing PCI were randomized to receive either the cost effective or a dedicated device, either of which were removed using patent hemostasis. Twenty-four hours after the procedure, radial artery ultrasonography was performed to evaluate the access site. The primary endpoint was assessed using a non-inferiority framework with a non-inferiority margin of five percentage points, which was considered as the least clinically meaningful difference. The cost-effective technique and the dedicated devices were associated with a comparably low rate of complications (freedom from DOCE: 83.3% vs. 70.8%, absolute risk difference: 12.5%, one-sided 95% confidence interval (CI): 1.11%). Composition of the DOCE (i.e., no complication, hematoma, pseudoaneurysm, and radial artery occlusion) and compression time were also assessed in superiority tests as secondary endpoints. Both the cost-effective technique and the dedicated devices were associated with comparably low rates of complications: p = 0.1289. All radial compression devices performed similarly when considering the time to complete removal of the respective device (120.0 (inter-quartile range: 100.0–142.5) for the vial vs. 120.0 (inter-quartile range: 110.0–180) for the dedicated device arm, with a median difference of [95% CI]: 7.0 [−23.11 to 2.00] min, p = 0.2816). In conclusion, our cost-effective method was found to be non-inferior to the dedicated devices with respect to safety, therefore it is a safe alternative to dedicated radial compression devices, as well as seeming to be similarly effective.

Objectives: The actual frequency and the risk factors of SARS-CoV-2 reinfection is still a matter of intense scientific discussion. In this case series, we report three elite athletes who underwent COVID-19 reinfection with a short time frame. Case presentations: As a part of contact tracing, three speed skaters (22-, 24-, and 29-year-old males) were found to be SARS-CoV-2 positive by polymerase chain reaction (PCR) tests. Later on, only one of the athletes experienced mild symptoms, such as fatigue, loss of smell and taste and subfebrility, while the other two athletes were asymptomatic. Following the quarantine period, detailed return-to-play examinations, including laboratory testing, ECG, 24-h Holter monitoring, transthoracic echocardiography and cardiac magnetic resonance imaging, revealed no apparent abnormality; therefore, the athletes restarted training. After a median of 74 days, all three athletes presented with typical symptoms of COVID-19, such as fever, marked fatigue and headache. SARS-CoV-2 PCR tests were performed again, showing recurrent positivity. Repeated return-to-play assessments were initiated, finding no relevant abnormality. Athletes were also tested for SARS-CoV-2 anti-nucleoprotein antibody titers, showing only modest increases following the second infection. Conclusions: We report a small cluster of elite athletes who underwent a PCR-proven SARS-CoV-2 reinfection. According to these findings, athletes may be considered as a high-risk group in terms of recurrent COVID-19.