Reduced endothelial progenitor cells and brachial artery flow‐mediated dilation as evidence of endothelial dysfunction in ocular hypertension and primary open‐angle glaucoma

Abstract

ABSTRACT.Purpose: This study aimed to assess vascular endothelial function in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG) by measuring: (a) endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery, and (b) circulating endothelial progenitor cells, which are believed to support the integrity of the vascular endothelium. Methods:We enrolled 25 patients with OHT, 23 with POAG and 26 control subjects, all of whom were aged < 65 years and had no medical history of cardiovascular disease or cardiovascular risk factors. All subjects underwent a complete ophthalmological examination, biochemistry study, assessment of cardiovascular parameters, brachial artery ultrasound assessment of endothelium-dependent FMD, generic circulating progenitor cell (CPC) and circulating endothelial progenitor cell (EPC) count with the use of flow cytometry.Results: Flow-mediated vasodilation values differed significantly in OHT (4.5 ± 1.1%; p = 0.021) and POAG (4.0 ± 0.9%; p = 0.003) patients compared with controls (7.7 ± 0.8%). The CD34 + KDR + EPC count was markedly lower in OHT (28.0 ± 5.0; p < 0.001) and POAG (24.3 ± 3.4; p < 0.001) patients compared with controls (73.1 ± 8.1). Neither FMD not EPCs differed significantly between OHT and POAG patients. No significant differences in CPC count or cardiovascular parameters were found among OHT or POAG patients and controls. The levels of CD34 + KDR + EPCs were directly correlated (p = 0.043) with FMD, and inversely correlated (p = 0.032) with baseline intraocular pressure in OHT and POAG patients.Conclusions: Both OHT and POAG patients without cardiovascular risk factors have previously unreported severely reduced circulating EPCs and reduced FMD, both of which are indicators of endothelial dysfunction and increased risk of cardiovascular events.

Nailfold Capillary Abnormalities in Primary Open-Angle Glaucoma: A Multisite Study

“…7 Endothelial progenitor cells are CD34 þ cells derived from the bone marrow that migrate to damaged endothelium for repair.…”

“…5 Furthermore, POAG patients across the spectrum of IOP show impaired brachial artery flow-mediated vasodilation. 6,7 Another marker of systemic vascular abnormalities is findings from nailfold capillary microscopy. Starting in the 1970s, nailfold capillaroscopy has been used to study the vascular component of various connective tissue diseases such as dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis.…”

“…There is evidence for dysfunction of Schlemm's canal endothelium 3 and systemic vascular endothelium [4][5][6][7] in POAG. For example, human Schlemm's canal endothelium generates nitric oxide in response to shear but this response was absent in comparable cells from two glaucomatous specimens.…”

Funktionelle Störungen im zeitlichen Verlauf der Glaukomerkrankung

“…Neben diesen direkten Stoffwechselstörungen sind weitere genetische Störungen [79] bekannt, die die zellulären Prozesse empfindlich beeinflussen. Zusätzlich wurde für das POWG als auch für das Normaldruckglaukom eine endotheliale Dysfunktion der Gefäße gefunden [10,23], und es konnte gezeigt werden, dass eine Störung der autoregulativen Kapazität der choroidalen Perfusion vorliegt [80].…”

Circulating progenitor cells are increased in newly diagnosed untreated hypertensive patients with arterial stiffening but normal carotid intima-media thickness

“…Circulating cells that expressed the stem cell antigens CD34, CD133 and CD34/CD133, but that lacked the endothelial lineage marker KDR were defined as generic CPCs, whereas CD34 + /KDR + and CD133 + /KDR + cells were identified as EPCs. 29 The cells were analyzed for the expression of surface antigens with direct three-color flow-cytometry analysis using fluorescein isothiocyanate-, phycoerythrin-and allophycocyanine-conjugated monoclonal antibodies (mAbs), as reported elsewhere. 30 Staining and analysis were performed using the International Society of Hematotherapy and Graft Engineering guidelines.…”