Reinier Boon - Academia.edu (original) (raw)

Papers by Reinier Boon

FEBS Letters, 2015

Keywords: microRNA Rab protein Microvesicle Exosome Endothelial cell a b s t r a c t By transport... more Keywords: microRNA Rab protein Microvesicle Exosome Endothelial cell a b s t r a c t By transporting regulatory RNAs like microRNAs, extracellular vesicles provide a novel layer of intercellular gene regulation. However, the underlying secretory pathways and the mechanisms of cargo selection are poorly understood. Rab GTPases are central coordinators of membrane trafficking with distinct members of this family being responsible for specific transport pathways.

Vascular Pharmacology, 2012

Atherosclerosis Supplements, 2010

Vascular Pharmacology, 2012

Hämostaseologie, 2009

Atherosclerotic plaque rupture and subsequent thrombosis is the main cause of sudden coronary dea... more Atherosclerotic plaque rupture and subsequent thrombosis is the main cause of sudden coronary death. Remarkably, atherosclerosis only develops in certain predisposed areas of the vasculature. Endothelial cells in these predisposed areas experience low or oscillatory shear stress, which activates the proinflammatory and procoagulant transcription factors activator protein 1 (AP-1) and nuclear factor kappaB (NFkappaB), thus inducing a proinflammatory, procoagulant surface. In contrast, healthy endothelial cells that are exposed to prolonged high laminar shear stress, express anti-inflammatory and anticoagulant genes. The key shear stress-induced transcription factors that govern the expression of these genes are Krüppel-like factor 2 (KLF2) and nuclear factor erythroid 2-like 2 (Nrf2). Together KLF2 and Nrf2 govern approximately 70% of the shear stress-elicited gene sets. Nrf2 potently induces anti-inflammatory/antioxidant enzymes, while KLF2 induces anti-inflammatory and anticoagulan...

Arteriosclerosis, thrombosis, and vascular biology, 2007

The flow-responsive Kruppel-like factor 2 (KLF2) is crucial for maintaining endothelial cell quie... more The flow-responsive Kruppel-like factor 2 (KLF2) is crucial for maintaining endothelial cell quiescence. Here, we describe its detailed effects on transforming growth factor-beta (TGF-beta) signaling, which normally has proatherogenic effects on endothelium. In-depth analysis of genome-wide expression data shows that prolonged lentiviral-mediated overexpression of KLF2 in human umbilical vein endothelial cells (HUVECs) diminishes the expression of a large panel of established TGF-beta-inducible genes. Both baseline and TGF-beta-induced expression levels of plasminogen activator inhibitor 1 (PAI-1) and thrombospondin-1 are greatly diminished by KLF2. Using a combination of ectopic expression, small interfering RNA-mediated knockdown, and promoter activity assays, we show that KLF2 partly inhibits the phosphorylation and subsequent nuclear accumulation of Smad2, thereby suppressing the TGF-beta-induced Smad4-mediated transcriptional activity. This is achieved through TGF-beta-independ...

Arteriosclerosis, thrombosis, and vascular biology, 2014

Journal of molecular and cellular cardiology, 2014

Nature reviews. Cardiology, 2015

MicroRNAs (miRNAs) are small noncoding RNAs that block translation or induce degradation of mRNA ... more MicroRNAs (miRNAs) are small noncoding RNAs that block translation or induce degradation of mRNA and thereby control patterns of gene expression. Acute myocardial infarction is a common cardiovascular event that results in cardiac remodelling and can consequently lead to the development of chronic heart failure. Several miRNAs have been shown to control important processes that contribute to the pathophysiological consequences of acute myocardial infarction. miRNAs can either promote or inhibit cardiomyocyte cell death, and also regulate postischaemic neovascularization. Cardiac regeneration can also be regulated by miRNAs that control cardiomyocyte proliferation or interfere with cardioprotective effects mediated by stem or progenitor cells. miRNAs can also be used for direct reprogramming of cardiac fibroblasts into cardiomyocytes. In this Review, we focus on the current understanding of the role of miRNAs in these processes, and particularly discuss the therapeutic potential of m...

Cardiovascular research, 2014

MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ... more MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ischaemia, but the effects of miR-92a on re-endothelialization and neointimal lesion formation after vascular injury remain elusive. We tested the effects of lowering miR-92a levels using specific locked nucleic acid (LNA)-based antimiRs as well as endothelial-specific knock out of miR-92a on re-endothelialization and neointimal formation after wire-induced injury of the femoral artery in mice. MiR-92a was significantly up-regulated in neointimal lesions following wire-induced injury. Pre-miR-92a overexpression resulted in repression of the direct miR-92a target genes integrin α5 and sirtuin1, and reduced eNOS expression in vitro. MiR-92a impaired proliferation and migration of endothelial cells but not smooth muscle cells. In vivo, systemic inhibition of miR-92a expression with LNA-modified antisense molecules resulted in a significant acceleration of re-endothelialization of the denude...

Abstract Coronary artery disease (CAD) patients have less circulating endothelial progenitor cell... more Abstract Coronary artery disease (CAD) patients have less circulating endothelial progenitor cells (EPCs), which exhibit impaired neovascularization properties. Inverse correlations were also found between EPC function and risk factors like age and diabetes. Krüppel-like ...

FEBS Letters, 2015

Keywords: microRNA Rab protein Microvesicle Exosome Endothelial cell a b s t r a c t By transport... more Keywords: microRNA Rab protein Microvesicle Exosome Endothelial cell a b s t r a c t By transporting regulatory RNAs like microRNAs, extracellular vesicles provide a novel layer of intercellular gene regulation. However, the underlying secretory pathways and the mechanisms of cargo selection are poorly understood. Rab GTPases are central coordinators of membrane trafficking with distinct members of this family being responsible for specific transport pathways.

Vascular Pharmacology, 2012

Atherosclerosis Supplements, 2010

Vascular Pharmacology, 2012

Hämostaseologie, 2009

Atherosclerotic plaque rupture and subsequent thrombosis is the main cause of sudden coronary dea... more Atherosclerotic plaque rupture and subsequent thrombosis is the main cause of sudden coronary death. Remarkably, atherosclerosis only develops in certain predisposed areas of the vasculature. Endothelial cells in these predisposed areas experience low or oscillatory shear stress, which activates the proinflammatory and procoagulant transcription factors activator protein 1 (AP-1) and nuclear factor kappaB (NFkappaB), thus inducing a proinflammatory, procoagulant surface. In contrast, healthy endothelial cells that are exposed to prolonged high laminar shear stress, express anti-inflammatory and anticoagulant genes. The key shear stress-induced transcription factors that govern the expression of these genes are Krüppel-like factor 2 (KLF2) and nuclear factor erythroid 2-like 2 (Nrf2). Together KLF2 and Nrf2 govern approximately 70% of the shear stress-elicited gene sets. Nrf2 potently induces anti-inflammatory/antioxidant enzymes, while KLF2 induces anti-inflammatory and anticoagulan...

Arteriosclerosis, thrombosis, and vascular biology, 2007

The flow-responsive Kruppel-like factor 2 (KLF2) is crucial for maintaining endothelial cell quie... more The flow-responsive Kruppel-like factor 2 (KLF2) is crucial for maintaining endothelial cell quiescence. Here, we describe its detailed effects on transforming growth factor-beta (TGF-beta) signaling, which normally has proatherogenic effects on endothelium. In-depth analysis of genome-wide expression data shows that prolonged lentiviral-mediated overexpression of KLF2 in human umbilical vein endothelial cells (HUVECs) diminishes the expression of a large panel of established TGF-beta-inducible genes. Both baseline and TGF-beta-induced expression levels of plasminogen activator inhibitor 1 (PAI-1) and thrombospondin-1 are greatly diminished by KLF2. Using a combination of ectopic expression, small interfering RNA-mediated knockdown, and promoter activity assays, we show that KLF2 partly inhibits the phosphorylation and subsequent nuclear accumulation of Smad2, thereby suppressing the TGF-beta-induced Smad4-mediated transcriptional activity. This is achieved through TGF-beta-independ...

Arteriosclerosis, thrombosis, and vascular biology, 2014

Journal of molecular and cellular cardiology, 2014

Nature reviews. Cardiology, 2015

MicroRNAs (miRNAs) are small noncoding RNAs that block translation or induce degradation of mRNA ... more MicroRNAs (miRNAs) are small noncoding RNAs that block translation or induce degradation of mRNA and thereby control patterns of gene expression. Acute myocardial infarction is a common cardiovascular event that results in cardiac remodelling and can consequently lead to the development of chronic heart failure. Several miRNAs have been shown to control important processes that contribute to the pathophysiological consequences of acute myocardial infarction. miRNAs can either promote or inhibit cardiomyocyte cell death, and also regulate postischaemic neovascularization. Cardiac regeneration can also be regulated by miRNAs that control cardiomyocyte proliferation or interfere with cardioprotective effects mediated by stem or progenitor cells. miRNAs can also be used for direct reprogramming of cardiac fibroblasts into cardiomyocytes. In this Review, we focus on the current understanding of the role of miRNAs in these processes, and particularly discuss the therapeutic potential of m...

Cardiovascular research, 2014

MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ... more MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ischaemia, but the effects of miR-92a on re-endothelialization and neointimal lesion formation after vascular injury remain elusive. We tested the effects of lowering miR-92a levels using specific locked nucleic acid (LNA)-based antimiRs as well as endothelial-specific knock out of miR-92a on re-endothelialization and neointimal formation after wire-induced injury of the femoral artery in mice. MiR-92a was significantly up-regulated in neointimal lesions following wire-induced injury. Pre-miR-92a overexpression resulted in repression of the direct miR-92a target genes integrin α5 and sirtuin1, and reduced eNOS expression in vitro. MiR-92a impaired proliferation and migration of endothelial cells but not smooth muscle cells. In vivo, systemic inhibition of miR-92a expression with LNA-modified antisense molecules resulted in a significant acceleration of re-endothelialization of the denude...

Abstract Coronary artery disease (CAD) patients have less circulating endothelial progenitor cell... more Abstract Coronary artery disease (CAD) patients have less circulating endothelial progenitor cells (EPCs), which exhibit impaired neovascularization properties. Inverse correlations were also found between EPC function and risk factors like age and diabetes. Krüppel-like ...