Incremental effects of diabetes mellitus and chronic kidney disease in medial arterial calcification: Synergistic pathways for peripheral artery disease progression

Diabetes mellitus (DM) and chronic kidney disease (CKD) separately are known to facilitate the progression of medial arterial calcification (MAC) in patients with symptomatic peripheral artery disease (PAD), but their combined effect on MAC and associated mediators of calcification is not well studi...

Full description

Saved in:
Bibliographic Details
Published in:Vascular medicine (London, England) England), 2019-10, Vol.24 (5), p.383-394
Main Authors: Krishnan, Prakash, Moreno, Pedro R, Turnbull, Irene C, Purushothaman, Meerarani, Zafar, Urooj, Tarricone, Arthur, Singla, Sandeep, Kini, Annapoorna, Sharma, Samin, Narula, Jagat, Badimon, Juan J, Purushothaman, K-Raman
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Alizarin
alpha-2-HS-Glycoprotein - analysis
Arteriosclerosis
Best management practices
Biomarkers - analysis
Bone morphogenetic protein 2
Bone Morphogenetic Protein 2 - analysis
Bone morphogenetic proteins
Calcification
Calcification (ectopic)
Cross-Sectional Studies
Density
Diabetes
Diabetes Complications - diagnosis
Diabetes Complications - etiology
Diabetes Complications - metabolism
Diabetes mellitus
Disease Progression
Female
Femoral Artery - chemistry
Humans
Immunohistochemistry
Kidney diseases
Kidneys
Male
Middle Aged
Peripheral Arterial Disease - diagnosis
Peripheral Arterial Disease - etiology
Peripheral Arterial Disease - metabolism
Plaques
Prognosis
Proteins
Renal Insufficiency, Chronic - complications
Renal Insufficiency, Chronic - diagnosis
Risk Assessment
Risk Factors
Therapeutic applications
Vascular Calcification - diagnosis
Vascular Calcification - etiology
Vascular Calcification - metabolism
Vascular diseases
Vascularization
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Diabetes mellitus (DM) and chronic kidney disease (CKD) separately are known to facilitate the progression of medial arterial calcification (MAC) in patients with symptomatic peripheral artery disease (PAD), but their combined effect on MAC and associated mediators of calcification is not well studied. The association of MAC and calcification inducer bone morphogenetic protein (BMP-2) and inhibitor fetuin-A, with PAD, is well known. Our aim was to investigate the association of MAC with alterations in BMP-2 and fetuin-A protein expression in patients with PAD with DM and/or CKD. Peripheral artery plaques (50) collected during directional atherectomy from symptomatic patients with PAD were evaluated, grouped into no-DM/no-CKD (n = 14), DM alone (n = 10), CKD alone (n = 12), and DM+CKD (n = 14). MAC density was evaluated using hematoxylin and eosin, and alizarin red stain. Analysis of inflammation, neovascularization, BMP-2 and fetuin-A protein density was performed by immunohistochemistry. MAC density, inflammation grade and neovessel content were significantly higher in DM+CKD versus no-DM/no-CKD and CKD (p < 0.01). BMP-2 protein density was significantly higher in DM+CKD versus all other groups (p < 0.01), whereas fetuin-A protein density was significantly lower in DM+CKD versus all other groups (p < 0.001). The combined presence of DM+CKD may be associated with MAC severity in PAD plaques more so than DM or CKD alone, as illustrated in this study, where levels of calcification mediators BMP-2 and fetuin-A protein were related most robustly to DM+CKD. Further understanding of mechanisms involved in mediating calcification and their association with DM and CKD may be useful in improving management and developing therapeutic interventions.
ISSN:1358-863X
1477-0377
DOI:10.1177/1358863X19842276