Increased Elastin Degradation in Pseudoxanthoma Elasticum Is Associated with Peripheral Arterial Disease Independent of Calcification

Jonas W Bartstra; Wilko Spiering; Jody M W van den Ouweland; Willem P T M Mali; Rob Janssen; Pim A de Jong

doi:10.3390/jcm9092771

Increased Elastin Degradation in Pseudoxanthoma Elasticum Is Associated with Peripheral Arterial Disease Independent of Calcification

J Clin Med. 2020 Aug 26;9(9):2771. doi: 10.3390/jcm9092771.

Authors

Jonas W Bartstra¹, Wilko Spiering², Jody M W van den Ouweland³, Willem P T M Mali¹, Rob Janssen⁴, Pim A de Jong¹

Affiliations

¹ Department of Radiology, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands.
² Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands.
³ Clinical Chemistry, Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands.
⁴ Department of Pulmonary Medicine, Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands.

Abstract

Pseudoxanthoma elasticum (PXE) results in extensive fragmentation and calcification of elastin fibers in the peripheral arteries, which results in peripheral arterial disease (PAD). Current research focuses on the role of calcifications in the pathogenesis of PXE. Elastin degradation and calcification are shown to interact and may amplify each other. This study aims to compare plasma desmosines, a measure of elastin degradation, between PXE patients and controls and to investigate the association between desmosines and (1) arterial calcification, (2) PAD, and (3) PAD independent of arterial calcification in PXE. Plasma desmosines were quantified with liquid chromatography-tandem mass spectrometry in 93 PXE patients and 72 controls. In PXE patients, arterial calcification mass was quantified on CT scans. The ankle brachial index (ABI) after treadmill test was used to analyze PAD, defined as ABI < 0.9, and the Fontaine classification was used to distinguish symptomatic and asymptomatic PAD. Regression models were built to test the association between desmosines and arterial calcification and arterial functioning in PXE. PXE patients had higher desmosines than controls (350 (290-410) ng/L vs. 320 (280-360) ng/L, p = 0.02). After adjustment for age, sex, body mass index, smoking, type 2 diabetes mellitus, and pulmonary abnormalities, desmosines were associated with worse ABI (β (95%CI): -68 (-132; -3) ng/L), more PAD (β (95%CI): 40 (7; 73) ng/L), and higher Fontaine classification (β (95%CI): 30 (6; 53) ng/L), but not with arterial calcification mass. Lower ABI was associated with higher desmosines, independent from arterial calcification mass (β (95%CI): -0.71(-1.39; -0.01)). Elastin degradation is accelerated in PXE patients compared to controls. The association between desmosines and ABI emphasizes the role of elastin degradation in PAD in PXE. Our results suggest that both elastin degradation and arterial calcification independently contribute to PAD in PXE.

Keywords: arterial calcification; peripheral arterial disease; plasma desmosines; pseudoxanthoma elasticum.