RESUMEN
Growing evidence suggests the crucial involvement of inflammation in the pathogenesis of pulmonary hypertension (PH). The current study analyzed the expression of interleukin (IL)-17a and IL-22 as potential biomarkers for PH in a preclinical rat model of PH as well as the serum levels in a PH patient collective. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in 10 Sprague Dawley rats (PH) and compared to 6 sham-treated controls (CON) as well as 10 monocrotalin-induced, macitentan-treated rats (PH_MAC). Lung and cardiac tissues were subjected to histological and immunohistochemical analysis for the ILs, and their serum levels were quantified using ELISA. Serum IL levels were also measured in a PH patient cohort. IL-22 expression was significantly increased in the lungs of the PH and PH_MAC groups (p = 0.002), whereas increased IL17a expression was demonstrated only in the lungs and RV of the PH (p < 0.05) but not the PH_MAC group (p = n.s.). The PH group showed elevated serum concentrations for IL-22 (p = 0.04) and IL-17a (p = 0.008). Compared to the PH group, the PH_MAC group demonstrated a decrease in IL-22 (p = 0.021) but not IL17a (p = n.s.). In the PH patient collective (n = 92), increased serum levels of IL-22 but not IL-17a could be shown (p < 0.0001). This elevation remained significant across the different etiological groups (p < 0.05). Correlation analysis revealed multiple significant relations between IL-22 and various clinical, laboratory, functional and hemodynamic parameters. IL-22 could serve as a promising inflammatory biomarker of PH with potential value for initial diagnosis, functional classification or even prognosis estimation. Its validation in larger patients' cohorts regarding outcome and survival data, as well as the probability of promising therapeutic target structures, remains the object of further studies.
Asunto(s)
Hipertensión Pulmonar , Humanos , Animales , Ratas , Ratas Sprague-Dawley , Hipertensión Pulmonar/diagnóstico , Interleucina-22 , Biomarcadores , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
Introduction. Due to the complex interaction between the underlying disease, psychosocial factors, and the high-dose hormonal therapy, transgender patients pose a therapeutic and diagnostic challenge, especially during emergencies. This case presents one such clinical dilemma using the example of a case of myocardial infarction. CASE: A 35-year-old transgender male presented to our clinic with an acute inferior wall myocardial infarction. For the past 6 years, he was receiving high-dose testosterone therapy for the maintenance of hormone levels after female-to-male gender conversion. The emergency coronary angiography revealed a distal right coronary artery occlusion. Recanalization of the vessel was achieved by catheter-driven direct thrombectomy and subsequent intracardiac lysis. The appearance of the remaining coronary arteries bore no angiographic evidence of advanced coronary artery disease. We suspected a thromboembolic origin as the primary cause of the myocardial infarction. The presentation also fulfilled the proposed National Cerebral and Cardiovascular Center criteria for the clinical diagnosis of coronary embolism. In the diagnostic work-up, the most common causes of coronary embolism like atrial fibrillation, cardiomyopathies, endocarditis, and intracardiac tumors could be ruled out. The screening for hereditary thrombophilia was also negative. Likewise, the presence of a haemodynamically relevant right to left shunt could be excluded. In the end, the high-dose testosterone therapy seemed to be the most likely cause. CONCLUSION: Following major thromboembolic cardiovascular events, we believe that transgender males treated with high-dose testosterone therapy should receive oral anticoagulation, preferably with a DOAC, especially keeping in mind that the discontinuation of the hormone therapy is not always possible due to the various underlying psychosocial factors.