There’s more to arteries of people with diabetes than meets the eye through the microscope

New findings indicate that increased basement membrane material is a general, but overlooked, phenomenon in arteries of people with type 2 diabetes.

Having diabetes more than doubles your risk of dying from ischemic heart disease irrespective of risk factors such as hypertension or hyperlipidaemia. Danish Diabetes Academy-funded researcher, Lasse Bach Steffensen (Postdoc at the University of Southern Denmark) and colleagues are working on the hypothesis that the increased risk is due to general changes in the arteries throughout the body in patients with diabetes. Recent studies back them up, and their latest findings indicate that increased basement membrane material is a general, but overlooked, phenomenon in arteries from people with type 2 diabetes.

To address their working hypothesis, the research team analysed different types of arteries – both with and without atherosclerosis (the underlying cause of ischemic heart disease) – obtained from surgical procedures performed on patients with type 2 diabetes and from patients without diabetes. By microscopic analysis, no differences were observed between arteries from the two patient groups, but by the use of mass spectrometry (a method to measure hundreds of proteins simultaneously) the research team found a distinct increase in so-called basement membrane proteins in arteries from the type 2 diabetes patient group.

“We have to say, our observations all indicate that increased basement membrane material is a general, but overlooked, phenomenon in arterial disease in people with type 2 diabetes.”

The basement membrane is a specialised type of extracellular matrix (the connective tissue surrounding cells), which exists in different compositions throughout the tissues of the body. In textbooks, the basement membrane is attributed an epithelium-supporting matrix, but basement membranes are also critical in many other types of tissue.

‘The arterial basement membrane is often neglected or forgotten, but the cells of the arterial wall are completely embedded in basement membrane that undoubtedly plays a significant role, says Lasse Bach Steffensen. He continues: ‘It is clear from our observations that increases in basement membrane proteins is a general, but overlooked, phenomenon in the arteries of patients with type 2 diabetes'.

The results were recently published in the journal Cardiovascular Diabetology, with Lasse sharing first authorship with Xenia Sinding Iversen and Rasmus Søgaard Hansen.

We have various ideas, but we really don’t know
In a parallel study published in Scientific Reports earlier this year, the research team altered the level of an important basement membrane protein (type IV collagen) in mice and found that the level of basement membrane proteins is an important determinant for the phenotype of vascular smooth muscle cells (the most prevalent cell type in the arterial wall).

‘How and why basement membrane proteins accumulate in arteries of patients with type 2 diabetes is something we have various ideas about, but we really don’t know. However, our ongoing studies will tell us whether the altered level plays a role in the development of atherosclerosis, and this will contribute to our understanding of the increased risk ischemic heart disease in people with diabetes’, says Lasse.

Collaboration with experts and dedicated staff
The studies are being supervised by Lasse’s mentor, Professor Lars Melholt Rasmussen, who is the head of the Artery Biobank at Odense University Hospital (OUH). ‘These types of studies are only feasible because of the huge efforts made every day by the dedicated staff of the OUH Artery Biobank’, says Lasse. ‘It’s a unique resource that’s much envied abroad’. He adds: ‘And then we are so fortunate to be collaborating with experts in mass spectrometry at the Department of Clinical Biochemistry and Pharmacology at OUH, who provide the foundation for many of our projects’.

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CONTACT:
Lasse Bach Steffensen
Postdoc, Cardiovascular and Renal Research Unit, University of Southern Denmark, Odense
https://orcid.org/0000-0001-6353-4227
Email: lsteffensen@health.sdu.dk

READ THE ARTICLES HERE:

(1) Scientific Reports
2021 Jun 18;11(1):12903.
doi: 10.1038/s41598-021-92303-y.

Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation
L B Steffensen  ^{1   2   3} , J Stubbe  ² , J S Lindholt  ^{1   4} , H C Beck  ³ , M Overgaard  ³ , M Bloksgaard  ² , F Genovese  ⁵ , S Holm Nielsen  ^{5   6} , M L T Tha  ¹ , S K Bang-Moeller  ² , M K T Hong Lin  ¹ , J H Larsen  ^{1   2   3} , D R Hansen  ^{1   2   3} , G T Jones  ⁷ , M J Bown  ^{4   8} , M A Karsdal  ⁵ , L M Rasmussen  ^{9   10}

Affiliations:
PMID: 34145342
PMCID: PMC8213747 
DOI: 10.1038/s41598-021-92303-y
________________________________________

(2) Cardiovasc Diabetol
2021 Sep 8;20(1):182.
doi: 10.1186/s12933-021-01375-7.

Basement membrane proteins in various arterial beds from individuals with and without type 2 diabetes mellitus: a proteome study
Lasse Bach Steffensen ^{#  1   2  3} , Xenia Emilie Sinding Iversen ^{#  1   2} , Rasmus Søgaard Hansen ^{#  1   2} , Pia Søndergaard Jensen  ^{1   2} , Anne-Sofie Faarvang Thorsen  ^{1   2} , Jes Sanddal Lindholt  ^{2   4} , Lars Peter Schødt Riber  ⁴ , Hans Christian Beck  ^{1   2} , Lars Melholt Rasmussen  ^{5   6}

Affiliations
PMID: 34496837
PMCID: PMC8428091 
DOI: 10.1186/s12933-021-01375-7