Pathophysiological background
Aortic aneurysms—localized dilations of the body’s main artery—are often silent until rupture, with catastrophic outcomes. Their development involves inflammation, vascular remodeling, and smooth muscle cell loss. While hypertension is a well-known risk factor, the influence of type 2 diabetes mellitus remains unclear.
Interestingly, epidemiological studies have indicated a lower prevalence of aortic aneurysms in patients with diabetes. The mechanisms behind this paradox are uncertain, prompting researchers from the University Medical Center Utrecht to examine immune cell and vascular patterns within aneurysmal aortic tissue.
Study design and methods
The investigation included 51 ascending aortic samples obtained during surgical repair. Nine specimens were from patients with type 2 diabetes and 42 from hypertensive patients without diabetes.
Histological staining identified mast cells (MCs) using CD117, smooth muscle cells, and vascular structures via von Willebrand factor. The aortic wall was assessed layer by layer—intima, media, and adventitia—for MC density and vascularity. Two independent blinded observers performed the quantification to ensure reliability.
Key histological findings
The authors reported that “The distribution of mast cells differed significantly between the groups.”
-
Diabetic samples exhibited fewer mast cells in the intima and more in the adventitia.
-
No significant difference was found in the medial layer.
-
Microvascular density did not differ significantly between the groups.
This pattern indicates that diabetes modifies not the overall mast cell number, but rather their spatial localization within the aortic wall.
Mechanistic interpretation
Mast cells play a dual role in inflammation and tissue remodeling. When activated, they release enzymes and cytokines that can degrade extracellular matrix components. In hypertensive aneurysms, MCs typically accumulate near the intima and contribute to wall weakening.
In contrast, their outward relocation in diabetes suggests a distinct inflammatory milieu. As the authors explain, “Mast cells in diabetes seem to relocate away from the intima, suggesting distinct mechanisms in aortic wall remodeling.”
Implications and future directions
The study provides histological evidence that type 2 diabetes and hypertension are associated with different immune and vascular responses in ascending aortic aneurysms. While the small sample size—especially in the diabetic group—limits firm conclusions, the findings highlight how metabolic conditions may shape vascular inflammation.
The authors note that further research with larger, mixed cohorts and additional mast cell markers could refine these observations and clarify potential protective mechanisms of diabetes in aneurysm development.
Summary and outlook
By revealing a shift in mast cell distribution from the intima to the adventitia in diabetic aortic aneurysms, this study adds new insight into how diabetes alters vessel wall pathology. These results suggest divergent pathogenic pathways for aneurysm formation in diabetic versus hypertensive patients, paving the way for more targeted investigations into vascular remodeling mechanisms.
The translation of the preceding English text in Slovenian:
Patofiziološko ozadje
Anevrizme aorte — lokalizirane razširitve glavne telesne arterije — so pogosto tihe, dokler ne pride do rupture, kar ima lahko katastrofalne posledice. Njihov razvoj vključuje vnetje, remodeliranje žilja in izgubo gladkih mišičnih celic. Medtem ko je hipertenzija dobro znan dejavnik tveganja, ostaja vpliv sladkorne bolezni tipa 2 nejasen.
Zanimivo je, da so epidemiološke študije pokazale manjšo pojavnost anevrizem aorte pri bolnikih s sladkorno boleznijo. Mehanizmi, ki stojijo za tem paradoksom, niso znani, zato so raziskovalci z Univerzitetnega medicinskega centra Utrecht preučevali vzorce imunskih celic in žilnih struktur v anevrizmalnem tkivu aorte.
Zasnova in metode raziskave
V raziskavo je bilo vključenih 51 vzorcev ascendentne aorte, pridobljenih med kirurško rekonstrukcijo. Devet vzorcev je bilo od bolnikov s sladkorno boleznijo tipa 2, 42 pa od hipertenzivnih bolnikov brez sladkorne bolezni.
Histološko barvanje je identificiralo mastocite (MC) z uporabo markerja CD117, gladke mišične celice in žilne strukture z uporabo von Willebrandovega faktorja. Stena aorte je bila ocenjena plast za plastjo — intima, media in adventicija — glede gostote mastocitov in žilnosti. Kvantifikacijo sta opravila dva neodvisna slepa opazovalca, kar je zagotovilo zanesljivost rezultatov.
Ključne histološke ugotovitve
Avtorji so poročali, da »je bila porazdelitev mastocitov med skupinama značilno različna.«
Vzorci diabetikov so pokazali manj mastocitov v intimi in več v adventiciji.
V medialni plasti ni bilo zaznati pomembnih razlik.
Gostota mikrožilja se med skupinama ni bistveno razlikovala.
Ta vzorec nakazuje, da sladkorna bolezen ne spreminja skupnega števila mastocitov, temveč njihovo prostorsko lokalizacijo v steni aorte.
Mehanistična razlaga
Mastociti imajo dvojno vlogo pri vnetju in remodeliranju tkiva. Ko se aktivirajo, sproščajo encime in citokine, ki lahko razgrajujejo komponente zunajceličnega matriksa. Pri hipertenzivnih anevrizmah se mastociti običajno kopičijo v bližini intime in prispevajo k oslabitvi stene.
Nasprotno pa njihova prerazporeditev navzven pri sladkorni bolezni nakazuje drugačno vnetno okolje. Kot pojasnjujejo avtorji: »Zdi se, da se mastociti pri sladkorni bolezni pomikajo stran od intime, kar nakazuje na različne mehanizme remodeliranja stene aorte.«
Pomen in prihodnje usmeritve
Študija prinaša histološke dokaze, da sta sladkorna bolezen tipa 2 in hipertenzija povezana z različnimi imunskimi in žilnimi odzivi pri ascendentnih anevrizmah aorte. Čeprav majhno število vzorcev — zlasti v skupini diabetikov — omejuje trdne zaključke, ugotovitve poudarjajo, kako lahko presnovna stanja oblikujejo žilno vnetje.
Avtorji poudarjajo, da bi nadaljnje raziskave z večjimi, mešanimi kohortami in dodatnimi markerji mastocitov lahko izpopolnile te ugotovitve ter pojasnile morebitne zaščitne mehanizme sladkorne bolezni pri razvoju anevrizem.
Povzetek in pogled naprej
Z razkritjem premika v porazdelitvi mastocitov iz intime proti adventiciji pri diabetičnih anevrizmah aorte ta študija ponuja nov vpogled v to, kako sladkorna bolezen spreminja patologijo žilne stene. Rezultati nakazujejo različne patogene poti pri nastanku anevrizem pri diabetičnih v primerjavi s hipertenzivnimi bolniki ter odpirajo pot ciljno usmerjenim raziskavam mehanizmov remodeliranja žilja.
Reference:
Aleš Pleskovič, Ruda Zorc-Pleskovič, Marjeta Zorc, Aleksandra Milutinović
Diabetes-induced redistribution of mast cells to the adventitia in ascending aortic aneurysms.
Biomol Biomed [Internet]. 2025 Jul. 29 [cited 2025 Nov. 3];25(12):2827–2834.
Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/12772
Additional information:
We invite submissions for our upcoming thematic issues, including:
- Immune Prediction and Prognostic Biomarkers in Immuno-Oncology
- Artificial Intelligence and Machine Learning in disease diagnosis and treatment target identification
More news: Blog
Editor: Merima Hadžić
Leave a Reply