Nephropathy and Diabetes in Degenerative Aortic Valve Disease: A Role for Small Leucine-Rich Proteoglycans?

Objectives: Small leucine-rich proteoglycans (SLRP) are known to be involved in processes of aortic valve disease. Own data show that especially biglycan expression is altered in degenerated aortic valves of diabetics and in valvular interstitial cells under hyperglycemia and degenerative conditions in vitro. It is also known that SLRP are involved in inflammatory and fibrotic mechanisms in nephropathies in the course of diabetes (DM). Thus, the aim of this study was to investigate whether SLRP could be a possible link between aortic valve disease and nephropathy in diabetes in a retrospective analysis.

Methods: Degenerated aortic valves and patient data collected of patients receiving aortic valve replacement (n = 73) were screened and patients with bicuspid aortic valves, type 1 diabetes and with a history of endocarditis, HIV and hepatitis B/C were excluded. Patients with renal insufficiency (RI) and DM or both were compared with a control group without RI and DM. Therefore, mRNA of aortic valves was isolated and gene expression was measured by RT-PCR. In detail, expression of the SLRP biglycan, decorin and lumican as well as of the downstream signaling targets TLR2 and TLR4 was analyzed and compared between these four groups: (1) control (n = 18), (2) RI (n = 16), (3) DM (n = 19) and (4) RI + DM (n = 20).

Result: Expression of biglycan, decorin, lumican, and TLR2/4 was significantly upregulated in aortic valves of patients with RI + DM compared with the control group. Moreover, biglycan, decorin, and both TLR showed a higher expression in the RI + DM group compared with the RI group.

Conclusion: This study shows that mRNA expression of SLRP and downstream targets is regulated in aortic valves of patients suffering from RI and DM. Thus, these molecules might be possible candidates as key factors in further analysis, potentially leading to an optimized patient management and preventing therapies.

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Publikationsverlauf

Artikel online veröffentlicht:
19. Februar 2021