Upalne stanice u stijenci aneurizme trbušne aorte aterosklerotskoga podrijetla [Inflammatory cells in the atherosclerotic abdominal aortic aneurysm]

Pažur, Vedran (2018) Upalne stanice u stijenci aneurizme trbušne aorte aterosklerotskoga podrijetla [Inflammatory cells in the atherosclerotic abdominal aortic aneurysm]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

The inflammatory reaction is defined as the key regulatory atherosclerotic process. By comparing the type and volume of inflammatory cells in the abdominal aortic aneurysm (AAA) walls and the only atherosclerotic abdominal aorta abnormalities, the influence of inflammation on the formation of atherosclerotic plaque and the development of ATA was investigated. Comparison of the type and volume of inflammatory cells - macrophage, mast cell, lymphocyte B, plasma cells, auxiliary CD4 + lymphocytes T, cytotoxic CD8 + lymphocytes, in the AAA strain (40 patients treated with open surgical aneurysm repair) and rocks only atherosclerotic altered abdominal aorta (20 patients) T and regulatory CD4 + Foxp3 + lymphocytes T. Inflammatory cells are characterized by the representation of specific cellular markers by immunohistochemical method on paraffinic tissue cuts. The morphological characteristics of AAA (diameter, morphological type - fusiform / saccular, isolated abdominal aorta aneurysm or extended with one and / or two iliac arteries , presence of intraluminal thrombus), laboratory parameters (CRP, D-dimer, total cholesterol (age, gender, body weight, body weight, body mass index (ITM), smoking, blood pressure - systolic/diastolic, diabetes mellitus, presence of peripheral atherosclerosis, other peripheral aneurysms), and clinical risk factors of atherosclerosis, taking medicines - statins). In the AAA strains, a significantly higher number of cytotoxic CD8 + lymphocytes T, regulatory CD4 + Foxp3 + lymphocytes T and plasma cells were found in comparison to the only atherosclerotic abdominal aortic ventricular wall. Significantly larger number of auxiliary CD4 + lymphocytes T and macrophages were found in the abdominal aorta of the control group. In the largest number of patients, the diameter of AAA was 45-75 mm, aneurysms were more often sacrilege (32/40), isolated without the involvement of one and/or two iliac arteries with branches (36/40) and with intraluminal thrombosis (28/40). By comparison of the type and volume of the examined inflammatory cells in the AAA strain and the morphological characteristics of the AAA, a statistically significant higher incidence of lymphocyte B was found in the fusiform type of AAA. The type and frequency of the examined inflammatory cells are not related to other analyzed morphological characteristics of AAA. By comparing the type and volume of the investigated inflammatory cells with the investigated laboratory indicators and clinical factors of atherosclerosis risk, statistically significant results of plasma cell-related correlation with LDL and total cholesterol, cytotoxic CD8 + lymphocyte T and plasma cells were found with diastolic pressure values and regulatory CD4 + Foxp3 + lymphocytes with ITM and body weight of patients have no specific clinical relevance. By comparing the morphological characteristics of AAA with the investigated laboratory indicators and the clinical factors of atherosclerosis risk, the AAA diameter was significantly associated with elevated CRP values. The extended AAA type with the involvement of one and/or two lipid arteries with the ribs was statistically significantly more frequent in elderly patients. The higher incidence of cytotoxic CD8 + lymphocytes T in AAA is responsible for damage to smooth muscle cells and the destruction of the aortic wall. The inflammatory reaction in atherosclerotic alteration of the abdominal aorta was characterized by a higher incidence of auxiliary CD4 + lymphocytes T and macrophages important in the initial stage and stimulation of inflammation. An increased number of regulatory CD4 + Foxp3 + T lymphocytes and AAA plasma cells suggests overcoming the inhibitory inflammatory response in AAA. Different characteristics of the inflammatory response in the parts only atherosclerotic aortic and aorta scars indicate changes in the characteristics of the inflammatory reaction with atherosclerosis and the emergence of aneurysmatic complications. The fusiform type of AAA is characterized by an increased inhibitory inflammatory response of lymphocytes B. The type and frequency of the examined inflammatory cells are not related to other morphological characteristics of the AAA diameter, isolated or extended aneurysm with the involvement of one and / or two iliac arteries with the branches and the presence of intraluminal thrombus. The AAA diameter is statistically significantly associated with elevated CRP values, indicating the importance of inflammation in atherosclerosis progression and the development of aneurysmatic complications. The extended AAA type with the involvement of one and/or two iliac arteries with the bra nches is significantly more frequent in elderly patients, pointing to the aetiology of AAA in elderly patients.

Abstract in Croatian

Upalna reakcija definirana je kao ključni regulatorni proces ateroskleroze. Usporedbom vrste i količine upalnih stanica u stijenci aneurizme trbušne aorte (ATA) i stijenci samo aterosklerotski promijenjene trbušne aorte istražen je utjecaj upale na stvaranje aterosklerotskog plaka i razvoj ATA. U stijenci ATA (40 bolesnika liječenih otvorenim kirurškim popravkom anurizme) i stijenci samo aterosklerotski promijenjene trbušne aorte (20 bolesnika) rađena je usporedba vrste i količine upalnih stanica - makrofaga, mastocita, limfocita B, plazma stanica, pomoćničkih CD4+ limfocita T, citotoksičnih CD8+ limfocita T i regulacijskih CD4+Foxp3+ limfocita T. Upalne stanice obilježene su prikazom specifičnih staničnih biljega imunohistokemijskom metodom na parafinskim rezovima tkiva. Također su analizirane morfološke karakteristike ATA (promjer, morfološki tip - fuziformna/sakularna, izolirana aneurizma trbušne aorte ili proširena sa zahvaćanjem jedne i/ili dvije ilijakalne arterije s ograncima, prisutnost intraluminalnog tromba), laboratorijski pokazatelji (CRP, D-dimer, ukupni kolesterol, HDL, LDL, trigliceridi) i klinički čimbenici rizika ateroskleroze (dob, spol, tjelesna visina, tjelesna težina, indeks tjelesne mase (ITM), pušenje, krvni tlak – sistolički/ dijastolički, šećerna bolest, prisutnost znakova periferne ateroskleroze, druga periferna aneurizma, uzimanje lijekova - statini). U stijenci ATA nađen je značajno veći broj citotoksičnih CD8+ limfocita T, regulacijskih CD4+Foxp3+ limfocita T i plazma stanica u odnosu na stijenku samo aterosklerotski promijenjene trbušne aorte. Značajno veći broj pomoćničkih CD4+ limfocita T i makrofaga nađen je u stijenci trbušne aorte kontrolne skupine. Kod najvećeg broja bolesnika promjer ATA je iznosio 45-75 mm, aneurizme su bile češće sakularnog oblika (32/40), izolirane bez zahvaćanja jedne i/ili dvije ilijakalne arterije s ograncima (36/40) i s prisutnim intraluminalnim trombom (28/40). Usporedbom vrste i količine ispitivanih upalnih stanica u stijenci ATA i morfoloških karakteristika ATA nađena je statistički značajna veća učestalost limfocita B u fuziformnom tipu ATA. Vrsta i učestalost ispitivanih upalnih stanica nisu povezane s ostalim analiziranim morfološkim karakteristikama ATA. Usporedbom vrste i količine ispitivanih upalnih stanica s ispitivanim laboratorijskim pokazateljima i kliničkim čimbenicima rizika za aterosklerozu, nađeni statistički signifikantni rezultati povezanosti plazma stanica s vrijednostima LDL i ukupnog kolesterola, citotoksičnih CD8+ limfocita T i plazma stanica s vrijednostima dijastoličkog tlaka i regulacijskih CD4+Foxp3+ limfocita s ITM i tjelesnom težinom bolesnika nemaju specifičan klinički značaj. Usporedbom morfoloških karakteristika ATA s ispitivanim laboratorijskim pokazateljima i kliničkim čimbenicima rizika za aterosklerozu vidjelo se da je promjer ATA značajno povezan s povišenom vrijednosti CRP. Prošireni tip ATA sa zahvaćanjem jedne i/ili dvije ilijakalne arterije s ograncima bio je statistički značajno češće prisutan u bolesnika starije životne dobi. Veća učestalost citotoksičnih CD8+ limfocita T u ATA odgovorna je za oštećenje glatkomišićnih stanica i destrukciju stijenke aorte. Upalna reakcija u samo aterosklerotski promijenjenoj stijenci trbušne aorte karakterizirana je većom učestalošću pomoćničkih CD4+ limfocita T i makrofaga važnih u početnoj fazi i poticanju upale. Povećan broj regulacijskih CD4+Foxp3+ limfocita T i plazma stanica u stijenci ATA ukazuje na prevladavanje inhibitornog upalnog odgovora u ATA. Različite karakteristike upalnog odgovora u stijenci samo aterosklerotski promijenjene aorte i stijenci ATA ukazuju na promjene karakteristika upalne reakcije s napredovanjem ateroskleroze i nastankom aneurizmatske komplikacije. Fuziformni tip ATA karakteriziran je povećanom inhibitornom upalnom reakcijom limfocita B. Vrsta i učestalost ispitivanih upalnih stanica nisu povezane s ostalim morfološkim karakteristikama ATA – promjer, izolirana ili proširena aneurizma sa zahvaćanjem jedne i/ili dvije ilijakalne arterije s ograncima i prisutnost intraluminalnog tromba. Promjer ATA statistički je značajno povezan s povišenom vrijednosti CRP što ukazuje na važnost upale u progresiji ateroskleroze i razvoju aneurizmatskih komplikacija. Prošireni tip ATA sa zahvaćanjem jedne i/ili dvije ilijakalne arterije s ograncima značajno češće je prisutan u bolesnika starije životne dobi, ukazujući na tezi klinički oblik ATA kod starijih bolesnika.

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