Pseudoexfoliative Glaucoma, Endothelial Dysfunction, and Arterial Stiffness: The Role of Circulating Apoptotic Endothelial Microparticles

J Glaucoma. 2019 Aug;28(8):749-755. doi: 10.1097/IJG.0000000000001303.

Abstract

PRéCIS:: Pseudoexfoliative glaucoma (PExG) patients present with not only endothelial dysfunction and arterial stiffness but also with a specific profile of circulating apoptotic endothelial microparticles which may be owing to the accumulation of pseudoexfoliative material in vessels walls.

Purpose: PExG is characterized by the deposition of pseudoexfoliative material in several tissues and organs including in the cardiovascular system. This study aimed to evaluate the vascular endothelial function, arterial stiffness, inflammatory status, and circulating microparticle (MP) levels in PExG patients compared with those in primary open-angle glaucoma (POAG) patients and control subjects.

Methods: Vascular endothelial function was evaluated by flow-mediated dilation. Pulse wave velocity and augmentation index were measured as indices of aortic stiffness and arterial wave reflections, respectively. Growth-differentiation factor-15 and intercellular adhesion molecule1 levels were measured to evaluate the systemic inflammatory status. Circulating MPs that constitute an emerging marker of vascular endothelial dysfunction and platelet activation were isolated and analyzed by flow cytometry.

Results: There was a stepwise impairment from the control to the POAG patients and PExG subjects in the flow-mediated dilation (8.21%±2.94% vs. 7.56%±3.12% vs. 5.79±3.13, P=0.005), pulse wave velocity (8.14±1.79 vs. 9.21±2.27 vs. 9.95±3.28 m/s, P=0.007), augmentation index (24.71%±7.84% vs. 26.78%±7.21% vs. 29.96%±7.58%, P=0.02), and growth-differentiation factor-15 (P=0.001) and intercellular adhesion molecule1 levels (P=0.08). PExG patients expressed greater levels of total circulating MPs (Annexin V+) (P=0.004) and endothelial-derived MPs (CD144+) (P<0.001) compared with POAG and control subjects.

Conclusions: PExG patients with an accumulation of pseudoexfoliative microfibrillar material presented with vascular endothelial dysfunction and arterial wall impairment associated with the levels of circulating proinflammatory molecules and circulating apoptotic endothelial MPs. These findings highlight the underlying systemic pathophysiological mechanisms associated with the progress of the pseudoexfoliative syndrome.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis / physiology*
  • Case-Control Studies
  • Cell-Derived Microparticles / pathology
  • Cell-Derived Microparticles / physiology*
  • Endothelial Cells / pathology
  • Endothelial Cells / physiology
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology*
  • Exfoliation Syndrome / complications
  • Exfoliation Syndrome / diagnosis
  • Exfoliation Syndrome / physiopathology*
  • Female
  • Glaucoma, Open-Angle / complications
  • Glaucoma, Open-Angle / diagnosis
  • Glaucoma, Open-Angle / physiopathology*
  • Humans
  • Intraocular Pressure / physiology
  • Male
  • Middle Aged
  • Pulse Wave Analysis
  • Vascular Diseases / complications
  • Vascular Diseases / diagnosis
  • Vascular Diseases / physiopathology
  • Vascular Stiffness / physiology*