Amber Korn1,2*, Mitchel D. Fiet1,2*, Hans W.M. Niessen2, Paul A.J. Krijnen1,2, Suat Simsek3,4
1Department of Pathology, Amsterdam University Medical Centre (AUMC), Amsterdam, The Netherlands. 2Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands. 3Department of Internal Medicine, Northwest Clinics, Alkmaar, The Netherlands. 4Department of Internal Medicine, AUMC, Amsterdam, The Netherlands.
*Authors had equal contribution.
Background: Diabetes mellitus (DM) is strongly associated with cardiac disease. Its prevalence, progression and pathophysiology is age-dependent and differs between men and women. A proper understanding of these processes might result in novel therapeutic interventions. A relatively new but important mediator in cardiac disease is the intramyocardial vasculature, especially the dysregulation of perivascular adipose tissue (PVAT) that is in part dependent on inflammation and oxidative stress. To investigate whether this is an important pathological factor in DM-related cardiac alterations, we have analysed PVAT in cardiac tissue of without pre-existing cardiac disease, including patients with and without DM of various age and both sexes.
Methods: Ventricular heart tissue was obtained during autopsy from 49 DM patients and 50 non-diabetic controls, which were later grouped per sex and age. In the intramyocardial vasculature we used EvG staining to assess PVAT, NOX2 staining to analyse oxidative stress, and CD45 (leukocyte) and CD68 (macrophage) staining to analyse inflammation.
Results: Patients with DM had a significantly higher percentage of perivascular fibrosis (p<0.0001) of the intramyocardial vasculature and NOX2+ vessels/mm2 (p=0.0002) in the myocardium compared to non-DM controls. This increase was visible in both men and women, as well as in all age groups. The percentage of CD45+ leukocytes and CD68+ macrophages in the perivascular tissue and the myocardium however was similar in the patients with DM compared to the non-DM controls.
Conclusion: The intramyocardial vasculature of patients with DM without pre-existing cardiac disease already shows alterations on a histological level that are associated with cardiac disease.