Vnetni in imunski odziv pri psih z miksomatozno degeneracijo mitralne zaklopke : raziskovalni podatki, obravnavani v doktorskem delu

Cimerman, Martina (avtor), Domanjko-Petrič, Aleksandra (mentor), Nemec Svete, Alenka (komentor), Druzhaeva, Natalia (raziskovalec), Ihan, Alojz (raziskovalec), Pohar, Katka (raziskovalec), Bajc, Miha (raziskovalec), Petek, Sara (raziskovalec), Baš, Anže (raziskovalec), Hajdinjak, Melita (raziskovalec), Krapež, Uroš (raziskovalec), Krt, Branko (raziskovalec), Dolinar, Klemen (raziskovalec), Miš, Katarina (raziskovalec), Pirkmajer, Sergej (raziskovalec)

Namen raziskave je bil proučiti razlike v deležih imunskih celic psov pri različnih stopnjah miksomatozne degeneracije mitralne zaklopke (MDMZ) ter v primerjavi z zdravimi psi in ugotoviti, ali imajo izbrani vnetni in imunski parametri napovedno vrednost. V prvem delu raziskave smo s Coxovo regresijsko analizo pri 62 psih z MDMZ ugotovili, da nevtrofilni granulociti, monociti in limfociti niso imeli napovedne vrednosti. Višja koncentracija citotoksičnih celic T je bila negativno povezana s preživetjem, medtem ko je bil delež celic T pomagalk pozitivno povezan s preživetjem v skupini psov z nestabilnim kongestivnim srčnim popuščanjem (KSP) ter skupini vseh psov z MDMZ. V prospektivnem delu raziskave smo pri 64 psih z MDMZ in 17 zdravih psih z metodo pretočne citometrije določili deleže podvrst limfocitov T, celic naravnih ubijalk ter monocitov in izmerili koncentracije citokinov in kemokinov (interlevkin (IL) 1β, IL-2, IL-6, IL-10, dejavnika tumorske nekroze α (TNF-α), keratinocitnega kemokina in monocitnega kemotaktičnega proteina 1 (MCP-1)). Delež aktiviranih celic T pomagalk je bil značilno nižji v skupini stabilnega KSP v primerjavi z ostalimi skupinami, medtem ko razlik v deležu citotoksičnih celic T ter regulacijskih celic T med skupinami ni bilo. Delež monocitov je bil značilno višji v skupini stabilnega in nestabilnega KSP v primerjavi s predklinično skupino, medtem, ko razlik v zastopanosti posameznih monocitnih podvrst med preiskovanimi skupinami ni bilo. Prav tako ni bilo razlik v deležih celic naravnih ubijalk. Za oceno medsebojnih povezav smo izračunali Spearmanove korelacijske koeficiente v skupini vseh psov z MDMZ in ugotovili negativno povezavo med monocitno podvrsto CD14⁻MHC II⁺ in MCP-1 ter pozitivno povezavo med monociti in MCP-1. Delež celic T pomagalk je bil negativno povezan s koncentracijami IL-6 ter TNF-α, medtem ko je bil delež citotoksičnih celic T pozitivno povezan s koncentracijo TNF-α. Slednje ugotovitve nakazuje vpletenost monocitov in citotoksičnih celic T pri vnetnem procesu MDMZ ter pozitivno vlogo celic T pomagalk v patogenezi MDMZ. Rezultati naše študije potrjujejo pomembno vlogo imunskega sistema pri patofiziologiji MDMZ.

• Jezik: Slovenski jezik
• Ključne besede: miksomatozna degeneracija mitralne zaklopke, pes, celice naravne ubijalke, regulacijske celice T, monociti, citokini, kemokini
• Tipologija: 2.20 - Zaključena znanstvena zbirka raziskovalnih podatkov
• Organizacija: VF - Veterinarska fakulteta
• Leto izida: 2025
• PID: 20.500.12556/RUL-175628
• Metode zbir. podat.: Intervju; Intervju: Osebno; Intervju: Telefon; Poskus; Poskus: Laboratorij; Združevanje; Meritve in testi; Meritve in testi: Fizično
• Datum objave v RUL: 06.11.2025

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Inflammatory and immune response in dogs with myxomatous mitral valve degeneration : research data underlying the doctoral dissertation

Izvleček

The aim of the study was to investigate differences in the proportions of immune cells in dogs at different stages of myxomatous mitral valve degeneration (MMVD) and in comparison with healthy dogs, and to determine whether selected inflammatory and immune parameters have predictive value. In the first part of the study, using Cox regression analysis in 62 dogs with MMVD, we found that neutrophil granulocytes, monocytes, and lymphocytes had no predictive value. Higher concentrations of cytotoxic T cells were negatively associated with survival, while the proportion of T helper cells was positively associated with survival in the group of dogs with unstable congestive heart failure (CHF) and in the group of all dogs with MMVD. In the prospective part of the study, we used flow cytometry to determine the proportions of T lymphocyte subtypes, natural killer cells, and monocytes in 64 dogs with MMVD and 17 healthy dogs, and measured the concentrations of cytokines and chemokines (interleukin (IL) 1β, IL-2, IL-6, IL-10, tumor necrosis factor α (TNF-α), keratinocyte chemotactic-like, monocyte chemoattractant protein-1 (MCP-1)). The proportion of activated T helper cells was significantly lower in the stable CHF group compared to the other groups, while there were no differences in the proportion of cytotoxic T cells and regulatory T cells between the groups. The proportion of monocytes was significantly higher in the stable and unstable CHF groups compared to the preclinical group, while there were no differences in the representation of individual monocyte subtypes between the groups studied. There were also no differences in the population of natural killer cells. To assess the interrelationships, we calculated Spearman's correlation coefficients in the group of all dogs with MMVD and found a negative correlation between the monocyte subtype CD14⁻MHC II⁺and MCP-1 and a positive correlation between monocytes and MCP-1. The proportion of T helper cells was negatively correlated with IL-6 and TNF-α concentrations, while the proportion of cytotoxic T cells was positively correlated with TNF-α concentration. These findings indicate the involvement of monocytes and cytotoxic T cells in the inflammatory process of MMVD and the positive role of T cells in the pathogenesis of MMVD. The results of our study confirm the important role of the immune system in the pathophysiology of MMVD.

• Ključne besede: myxomatous mitral valve degeneration, dog, natural killer cells, regulatory T cells, monocytes, cytokines, chemokines

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P4-0053
• Naslov: Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih