| Abstract | Cilj istraživanja: Ispitati povezanost ekspresije TLR4 na perifernim monocitima i razine interleukina 17A u serumu sa primarnom arterijskom hipertenzijom, istražiti povezanost duljine trajanja hipertenzije i vrste antihipertenzivne terapije sa ekspresijom TLR4 i razinom interleukina 17A. Nacrt studije: Istraživanje je koncipirano kao presječna usporedna studija. Ispitanici i metode: U studiju je bilo uključeno 105 ispitanika koji su bili podijeljeni u dvije skupine. U prvoj skupini bila su 52 ispitanika sa nereguliranom primarnom arterijskom hipertenzijom. U drugoj, kontrolnoj, skupini bila su 53 bolesnika sa dobro reguliranom AH. Svim ispitanicima je protočnom citometrijom određena ekspresija TLR4, a razinu IL-17A ELISA metodom. Povišenim tlakom smatrao se tlak veći od 140/90 mmHg, sukladno smjernicama ESH/ESC iz 2013. godine. Svim ispitanicima uzeta je kompletna anamneza, podaci o lijekovima, fizikalni status i laboratorijski nalazi. Laboratorijski i slikovno je isključena sekundarna arterijska hipertenzija. Bubrežna funkcija se procjenjivala iz nalaza klirensa endogenog kreatinina i proteinurije, te korištenjem CKD-Epi formule za izračun glomerularne filtracije. Rezultati: izražaj TLR4 veći u grupi ispitanika sa nereguliranom hipertenzijom (25.60 vs. 21.99, P=0.011) . Duljina trajanja bolesti u toj istoj skupini povezana je sa višom razinom IL-17A (=0.566, P<0.001). U grupi ispitanika sa dobro reguliranim tlakom duljina trajanja bolesti je povezana sa većom ekspresijom TLR4 (=0.322, P=0.020). Kod svih ispitanika koji u terapiji imaju tiazidski diuretik značajno je viša razina IL-17A, a to je bilo nešto jače izraženo u grupi ispitanika sa nereguliranom hipertenzijom (1.41 vs. 2.01 pg/ml, P<0.001; controlled 1.3 vs. 1.8 pg/ml, P= 0.023; non-controlled 1.6 vs. 2.3 pg/ml, P=0.001). U grupi sa dobro reguliranom hipertenzijom slabiji izražaj TLR4 bio je povezan sa beta-blokatorima (18.9 vs. 24.1, P=0.001). U grupi svih ispitanika, oni koji u terapiji imaju centralni antiadrenergik, razina IL-17A je značajno viša (1.69 vs. 2.1 pg/ml, P = 0,01) Lijekovi iz grupe ACE inhibitora i blokatora angiotenzinskih receptora nisu značajnije mijenjali ekspresiju TLR4 ili razinu IL-17A. Nismo našli povezanost izražaja TLR4 i IL-17A. Zaključak: Možemo reći da sama arterijska hipertenzija, kao i njeno trajanje te odabir antihipertenzivne terapije moduliraju imunološki status čak i onda kada se smatra da su vrijednosti tlaka dobro regulirane. |
| Abstract (english) | Objectives: We evaluated TLR4 expression on peripheral monocytes, IL-17A serum concentration in hypertensive patients. We also evaluated if the type of the used anti-hypertension drugs influenced TLR4 expression or IL-17A concentration and if hypertension duration contributed to TLR4 expression or IL-17A serum concentration.Study design: observational cross-sectional case control study. Material and methods: We enrolled 105 non-complicated otherwise healthy hypertensive patients: 53 controlled and 52 non-controlled. TLR4 peripheral monocyte expression and serum IL-17A levels were determined by flow cytometry and ELISA, respectively. Unregulated hypertensive patients where those with the blood pressure over 140/90 mmHg according to the „2013 ESH/ESC Guidelines for the management of arterial hypertension“. Complete medical history was obtained from the patients and they received a complete clinical examination as well as routine laboratory analysis. Secondary hypertension was excluded usig laboratory and radiological imaging methods. Results: Non-controlled patients exhibited higher TLR4 expression than controlled (25.60 vs. 21.99, P=0.011). TLR4 expression was lower in controlled patients who were prescribed beta blockers (18.9 vs. 24.1, P=0.001) and IL-17A concentration was higher in patients using diuretics in either group (1.41 vs. 2.01 pg/ml, P<0.001; controlled 1.3 vs. 1.8 pg/ml, P= 0.023; non-controlled 1.6 vs. 2.3 pg/ml, P=0.001) or central antiadrenergics (1.69 vs. 2.1 pg/ml, P = 0,01) Correlation between IL-17A concentration and hypertension duration was observed in non-controlled patients (Spearman Coeff. Corr. =0.566, P<0.001) whereas in controlled a correlation was found between hypertension duration and TLR4 expression (=0.322, P=0.020). We found no correlation between IL17 level and TLR 4 expression. No significant differences were observed in TLR4 expression or IL-17A levels in the patients who received ACE inhibitors and AT1 receptor blockers. Conclusion: Arterial hypertension stimulates the immune response regardless of regulation status. Prolonged hypertension influences peripheral monocyte TLR4 expression and IL-17A serum levels. Anti-hypertensive drugs have different immunomodulatory effects: diuretics are associated with higher IL-17A concentration and beta-blockers with lower TLR4 expression. |
