Imbalance between endothelial injury and repair in patients with polymyalgia rheumatica: improvement with corticosteroid treatment.
OBJECTIVE
Polymyalgia rheumatica (PMR) is a rheumatic disease that is characterized by intense activation of systemic inflammation. Systemic inflammation has been associated with an imbalance between endothelial injury and repair, defined by an increased number of circulating endothelial microparticles (EMPs) and a reduced number of endothelial progenitor cells (EPCs). We investigated the association between inflammation and endothelial injury and repair in patients with PMR and evaluated the effects of corticosteroid therapy on EMP and EPC levels.


METHODS
We conducted a case-control study in 34 patients with never-treated active PMR and 34 healthy age- and sex-matched controls. Patients with PMR participated in a 1-month intervention open-label study with corticosteroid therapy. Circulating EMPs (CD31+/CD42-) and EPCs (CD34+/KDR+) were quantified by fluorescence-activated cell sorting analysis.


RESULTS
Patients with PMR had an increased EMP/EPC ratio compared with controls [median (IQR): 6.5 (3.0-11.5) vs. 1.1 (0.7-1.5), P < 0.001], because of both increased EMP and reduced EPC levels. Levels of C-reactive protein (CRP) were associated with an increased EMP/EPC ratio (β = 0.48, P = 0.001), irrespective of traditional cardiovascular risk factors. Corticosteroid therapy led to a significant CRP reduction [from 3.9 (1.5-6.7) to 0.6 (0.2-1.2) mg dL(-1) , P < 0.05], paralleled by a consistent 81% decline in the EMP/EPC ratio. CRP and EMP/EPC ratio reductions were significantly correlated (rho = 0.37, P = 0.04).


CONCLUSIONS
Polymyalgia rheumatica is associated with a significant imbalance between endothelial injury and repair, which is dependent on the degree of systemic inflammation. Attenuation of inflammation by short-term corticosteroid therapy might have a role in limiting endothelial fragmentation and promote endothelial repair.
Unit of Internal Medicine, Angiology and Arteriosclerosis, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
M
M
Pirro
E B
EB
Bocci
F
F
Di Filippo
G
G
Schillaci
M R
MR
Mannarino
F
F
Bagaglia
R
R
Gerli
E
E
Mannarino
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D016903:Drug Monitoring / Q000379:methods; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000293:injuries / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D011111:Polymyalgia Rheumatica / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D012038:Regeneration / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D002097:C-Reactive Protein