The role of pulsatile flow in controlling microvascular retinal endothelial and pericyte cell apoptosis and proliferation

Tony E Walshe, Paul Connell, Lorna Cryan, Gail Ferguson, Colm O'Brien, Paul A Cahill

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

AIMS: Aberrant retinal blood flow is a hallmark of various retinopathies and may be a causative factor in the pathology associated with these conditions. We examined the effects of pulsatile flow on bovine retinal endothelial cell (BREC) and bovine retinal pericyte (BRP) apoptosis and proliferation.

METHODS AND RESULTS: Co-cultured BRECs and BRPs were exposed to low (0.3 mL/min) or high (25 mL/min) pulsatile flow for 72 h using a perfused transcapillary culture system. Pulsatile flow increased BREC nitric oxide synthase (eNOS) and cyclooxygenase-2 (COX-2) expression and activity concomitant with a significant decrease in pre-pro-endothelin-1 (ET-1) mRNA and peptide. BREC apoptosis was significantly attenuated following exposure to high flow. The inhibition of NOS, COX, and ET receptors significantly reduced the pro-survival effects of flow on BREC. In contrast, BRP apoptosis was significantly enhanced following exposure to high flow. The inhibition of COX and ET receptors significantly attenuated the high flow-induced increase in BRP apoptosis when compared with untreated controls. Treatment of static BREC with NO donor (S-nitroso-N-acetylpenicillamine, SNAP), ET-1, or iloprost inhibited serum deprivation-induced apoptosis, whereas treatment of BRP with ET-1 and iloprost, but not SNAP, was ineffective. High pulsatile flow decreased BRP proliferation, in the absence of any changes in BREC proliferation.

CONCLUSION: Increased pulsatile flow promotes BREC survival and enhances BRP apoptosis through the activation of endothelial-derived vasoactive substances. Altered pulsatile flow does not alter BREC proliferation in co-culture with BRP, whereas BRP proliferation was significantly decreased at high flow rates. These interactions have important implications for vessel growth and regression during retinal vascular pathogenesis.

Original languageEnglish
Pages (from-to)661-70
Number of pages10
JournalCardiovascular Research
Volume89
Issue number3
DOIs
Publication statusPublished - 15 Feb 2011

Fingerprint

Pulsatile Flow
Pericytes
Endothelial Cells
Cell Proliferation
Apoptosis
Endothelin-1
S-Nitroso-N-Acetylpenicillamine
Iloprost
Retinal Vessels
Nitric Oxide Synthase Type III
Cyclooxygenase 2
Coculture Techniques

Keywords

  • Animals
  • Apoptosis/physiology
  • Cattle
  • Cell Division/physiology
  • Cells, Cultured
  • Coculture Techniques
  • Endothelial Cells/cytology
  • Endothelin-1/metabolism
  • Epoprostenol/metabolism
  • Microcirculation/physiology
  • Nitric Oxide/metabolism
  • Pericytes/cytology
  • Pulsatile Flow/physiology
  • Regional Blood Flow/physiology
  • Retina/cytology
  • Retinal Vessels/cytology
  • Stress, Mechanical

Cite this

Walshe, Tony E ; Connell, Paul ; Cryan, Lorna ; Ferguson, Gail ; O'Brien, Colm ; Cahill, Paul A. / The role of pulsatile flow in controlling microvascular retinal endothelial and pericyte cell apoptosis and proliferation. In: Cardiovascular Research. 2011 ; Vol. 89, No. 3. pp. 661-70.
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The role of pulsatile flow in controlling microvascular retinal endothelial and pericyte cell apoptosis and proliferation. / Walshe, Tony E; Connell, Paul; Cryan, Lorna; Ferguson, Gail; O'Brien, Colm; Cahill, Paul A.

In: Cardiovascular Research, Vol. 89, No. 3, 15.02.2011, p. 661-70.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The role of pulsatile flow in controlling microvascular retinal endothelial and pericyte cell apoptosis and proliferation

AU - Walshe, Tony E

AU - Connell, Paul

AU - Cryan, Lorna

AU - Ferguson, Gail

AU - O'Brien, Colm

AU - Cahill, Paul A

PY - 2011/2/15

Y1 - 2011/2/15

N2 - AIMS: Aberrant retinal blood flow is a hallmark of various retinopathies and may be a causative factor in the pathology associated with these conditions. We examined the effects of pulsatile flow on bovine retinal endothelial cell (BREC) and bovine retinal pericyte (BRP) apoptosis and proliferation.METHODS AND RESULTS: Co-cultured BRECs and BRPs were exposed to low (0.3 mL/min) or high (25 mL/min) pulsatile flow for 72 h using a perfused transcapillary culture system. Pulsatile flow increased BREC nitric oxide synthase (eNOS) and cyclooxygenase-2 (COX-2) expression and activity concomitant with a significant decrease in pre-pro-endothelin-1 (ET-1) mRNA and peptide. BREC apoptosis was significantly attenuated following exposure to high flow. The inhibition of NOS, COX, and ET receptors significantly reduced the pro-survival effects of flow on BREC. In contrast, BRP apoptosis was significantly enhanced following exposure to high flow. The inhibition of COX and ET receptors significantly attenuated the high flow-induced increase in BRP apoptosis when compared with untreated controls. Treatment of static BREC with NO donor (S-nitroso-N-acetylpenicillamine, SNAP), ET-1, or iloprost inhibited serum deprivation-induced apoptosis, whereas treatment of BRP with ET-1 and iloprost, but not SNAP, was ineffective. High pulsatile flow decreased BRP proliferation, in the absence of any changes in BREC proliferation.CONCLUSION: Increased pulsatile flow promotes BREC survival and enhances BRP apoptosis through the activation of endothelial-derived vasoactive substances. Altered pulsatile flow does not alter BREC proliferation in co-culture with BRP, whereas BRP proliferation was significantly decreased at high flow rates. These interactions have important implications for vessel growth and regression during retinal vascular pathogenesis.

AB - AIMS: Aberrant retinal blood flow is a hallmark of various retinopathies and may be a causative factor in the pathology associated with these conditions. We examined the effects of pulsatile flow on bovine retinal endothelial cell (BREC) and bovine retinal pericyte (BRP) apoptosis and proliferation.METHODS AND RESULTS: Co-cultured BRECs and BRPs were exposed to low (0.3 mL/min) or high (25 mL/min) pulsatile flow for 72 h using a perfused transcapillary culture system. Pulsatile flow increased BREC nitric oxide synthase (eNOS) and cyclooxygenase-2 (COX-2) expression and activity concomitant with a significant decrease in pre-pro-endothelin-1 (ET-1) mRNA and peptide. BREC apoptosis was significantly attenuated following exposure to high flow. The inhibition of NOS, COX, and ET receptors significantly reduced the pro-survival effects of flow on BREC. In contrast, BRP apoptosis was significantly enhanced following exposure to high flow. The inhibition of COX and ET receptors significantly attenuated the high flow-induced increase in BRP apoptosis when compared with untreated controls. Treatment of static BREC with NO donor (S-nitroso-N-acetylpenicillamine, SNAP), ET-1, or iloprost inhibited serum deprivation-induced apoptosis, whereas treatment of BRP with ET-1 and iloprost, but not SNAP, was ineffective. High pulsatile flow decreased BRP proliferation, in the absence of any changes in BREC proliferation.CONCLUSION: Increased pulsatile flow promotes BREC survival and enhances BRP apoptosis through the activation of endothelial-derived vasoactive substances. Altered pulsatile flow does not alter BREC proliferation in co-culture with BRP, whereas BRP proliferation was significantly decreased at high flow rates. These interactions have important implications for vessel growth and regression during retinal vascular pathogenesis.

KW - Animals

KW - Apoptosis/physiology

KW - Cattle

KW - Cell Division/physiology

KW - Cells, Cultured

KW - Coculture Techniques

KW - Endothelial Cells/cytology

KW - Endothelin-1/metabolism

KW - Epoprostenol/metabolism

KW - Microcirculation/physiology

KW - Nitric Oxide/metabolism

KW - Pericytes/cytology

KW - Pulsatile Flow/physiology

KW - Regional Blood Flow/physiology

KW - Retina/cytology

KW - Retinal Vessels/cytology

KW - Stress, Mechanical

U2 - 10.1093/cvr/cvq341

DO - 10.1093/cvr/cvq341

M3 - Article

C2 - 21030535

VL - 89

SP - 661

EP - 670

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 3

ER -