THE ROLE OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN DIABETES-INDUCED MULTIORGAN DAMAGE
Molnár Ágnes
Clinical Medicine
Dr. Fekete Andrea
SE I. Gyermekgyógyászati Klinika tanterme
2026-01-28 14:00:00
Prevention of Chronic Diseases in Childhood
Dr. Szabó Attila
Dr. Fekete Andrea
Dr. Ledó Nóra
Dr. Légrády Péter
Dr. Sebestyén Anna
Dr. Pintér István
Dr. Cseprekál Orsolya
DKD is one of the most common and detrimental consequences of DM, associated with CVD and comorbid depression. International guidelines list RAASi as the gold-standard therapy, although it is still unclear whether their protective properties are associated with or restricted to their antihypertensive effect. The exact molecular pathways have not yet been fully explored in T1DM.
Our primary goal was to explore the underlying mechanisms of the pleiotropic effect of monotherapeutic nondepressor-dose RAASi as protection against T1DM‐induced renal, cardiac, and cerebral complications with special focus on fibrosis and inflammation.
Our previous experiments resulted in highly scattered data due to focal fibrosis, so we experimented with lyophilization during sample processing. We confirmed that using powdered homogenized samples improves the precision of measurements.
Firstly, in vitro experiments revealed that monotherapeutic RAASi have antifibrotic properties, mitigate O-GlcNAcylation in hyperglycaemic proximal tubular cells, and inhibit the growth factor-induced activation of fibroblast cells.
We also showed in vivo that monotherapeutic non-depressor dose RAASi treatment is renoprotective and antifibrotic in T1DM rats, and can also be monitored non-invasively by urinary biomarkers. Moreover, as part of CVD protection, RAASi attenuated arterial wall thickening, arterial stiffness increment, cardiac tissue damage and fibrosis without blood pressure changes. Furthermore, low-dose RAASi treatment also interfered with inflammatory pathways in the diabetic heart and brain. RAASi alleviated neuroinflammation and altered BDNF transformation by restoring cleavage enzymes in the hippocampi.
Our results provide evidence for the antifibrotic and anti-inflammatory properties of a non-depressor dose of RAASi, offering a possible novel therapeutic indication for them in T1DM-associated renal and cardiac complications. Our findings also support the link between DM and depression, where monotherapeutic RAASi can target neuroinflammation and the BDNF pathway. Furthermore we also emphasize that lyophilisation can be a superior sample processing method for higher reproducibility in case of focal lesions such as fibrosis.
