Abstract
BackgroundBasement 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.MethodsHuman 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)).ResultsWe 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.ConclusionOur 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.
Highlights
It is estimated that more than 463 million people worldwide are living with diabetes mellitus (DM) [1], and the global prevalence of DM continues to increase [2]
The type 2 DM (T2DM) groups had on average higher HbA1c, but overall, they did not differ from non-DM controls regarding other biochemical measures or blood pressure
The primary focus of the study was to assess effects on Basement membrane (BM) proteins, as we previously found BM to be enriched in bulk internal thoracic arteries (ITA) samples from T2DM patients [15]
Summary
It is estimated that more than 463 million people worldwide are living with diabetes mellitus (DM) [1], and the global prevalence of DM continues to increase [2]. The Steffensen et al Cardiovasc Diabetol (2021) 20:182 arterial wall in diabetes has been shown to harbor several generalized pathologies such as linear media calcifications [5, 6], increased stiffness [7], accumulation of nonenzymatically glycated substances [8] and dysfunctional remodeling of coronary arteries [9]. These observations seem to indicate that macrovascular disease in diabetes contain specific generalized elements, which may lead to the clinical cardiovascular conditions. 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
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