Basement membrane proteins in various arterial beds from individuals with and without type 2 diabetes mellitus: a proteome study

Abstract

Background Basement membrane (BM) accumulation is a hallmark of micro-vessel disease in diabetes mellitus (DM). We previously reported marked upregulation of BM components in internal thoracic arteries (ITAs) from type 2 DM (T2DM) patients by mass spectrometry. Here, we first sought to determine if BM accumulation is a common feature of different arteries in T2DM, and second, to identify other effects of T2DM on the arterial proteome. Methods Human arterial samples collected during heart and vascular surgery from well-characterized patients and stored in the Odense Artery Biobank were analysed by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). We included ascending thoracic aortas (ATA) (n = 10 (type 2 DM, T2DM) and n = 10 (non-DM)); laser capture micro-dissected plaque- and media compartments from carotid plaques (n = 10 (T2DM) and n = 9 (non-DM)); and media- and adventitia compartments from ITAs (n = 9 (T2DM) and n = 7 (non-DM)). Results We first extended our previous finding of BM accumulation in arteries from T2DM patients, as 7 of 12 pre-defined BM proteins were significantly upregulated in bulk ATAs consisting of > 90% media. Although less pronounced, BM components tended to be upregulated in the media of ITAs from T2DM patients, but not in the neighbouring adventitia. Overall, we did not detect effects on BM proteins in carotid plaques or in the plaque-associated media. Instead, complement factors, an RNA-binding protein and fibrinogens appeared to be regulated in these tissues from T2DM patients. Conclusion Our results suggest that accumulation of BM proteins is a general phenomenon in the medial layer of non-atherosclerotic arteries in patients with T2DM. Moreover, we identify additional T2DM-associated effects on the arterial proteome, which requires validation in future studies.

Mechanisms of Diabetic Nephropathy Not Mediated by Hyperglycemia

“…Proteome analysis of the basement membrane of arteries in T2DM shows an enrichment of typical proteins in arteries [71,74], that is a basement membrane accumulation in both small and large vessels.…”

“…The basement membrane can be considered a condensation of the connective tissue adjacent to an epithelium such as the endothelium. It is composed of collagen type VII, type III and type IV, fibrillin, perlecan, laminin, nidogen, integrins, entactins, and dystroglycans [71]. The basement membrane anchors the epithelium to the connective tissue: any alteration will cause detachment of the epithelium with formation of atheroma (in blood vessels), tubular atrophy, proteinuria, deposition of collagen under the capillaries (Kimmelstiel Wilson nodules), and several other phenomena typical of diabetes.…”

Protection of diabetes in aortic abdominal aneurysm: Are antidiabetics the real effectors?

“…However, hyperglycemia has been shown to stabilize the collagen network by generating a thicker aortic wall which exert a protective effect on the wall stress in the abdominal aorta of patients with DM ( 23 , 59 ). In this regard, accumulation of collagen IV is commonly observed in human diabetic arteries ( 60 , 61 ), while its deficiency is associated with AAA development ( 62 ). Moreover, circulating collagen IV degradation fragments correlated with AAA progression in the VIVA cohort ( 62 ).…”