Endothelial-Dependent Mechanisms of Leukocyte Recruitment to the Vascular Wall

Rao, Ravi Mohan; Yang, Lin; García‐Cardeña, Guillermo; Luscinskas, Francis W.

doi:10.1161/circresaha.107.151860b

Cited by 355 publications

(285 citation statements)

References 125 publications

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“…The sequential steps of rolling, adhesion, and transmigration mediate this process via the activity of specific families of adhesion molecules that characterize each step (Butcher 1991, Springer 1994, Rao et al 2007, Zarbock & Ley 2008. There is some evidence, from diverse animal models of inflammation, to suggest the existence of sex hormone-dependent male/female differences in leukocyte recruitment (Squadrito et al 1997, Simoncini et al 2000b, Eckhoff et al 2002 with evidence supporting the thesis that estrogens have the capacity to alter all stages of the recruitment process.…”

Section: Sex Differences In Leukocyte Recruitmentmentioning

confidence: 99%

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Villar¹,

Hobbs²,

Ahluwalia

2008

Journal of Endocrinology

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The vascular endothelium plays a crucial role in the regulation of vascular homeostasis by controlling vascular tone, coagulation, and inflammatory responses. These actions are exerted by endothelial factors including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The greater incidence of cardiovascular disease (CVD) in men and postmenopausal women compared with premenopausal women implies a vasoprotective phenotype of females, which may be influenced by sex hormones. These hormones, particularly estrogen, have modulatory effects on the endothelium and circulating cells that have been implicated in vascular inflammation and in the development of CVD. EDHF seems to be the predominant endothelial factor in the resistance vasculature of females and this mediator could afford the beneficial cardiovascular risk profile observed in premenopausal woman. In this review, we discuss sex differences in EDHF biology and how sex hormones can modulate EDHF responses. We also review the implication of sex hormone-dependent regulation of EDHF in inflammatory processes, platelet function, and repair after vascular damage, each of which have a critical role in several aspects of the pathogenesis of CVD.

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Section: Sex Differences In Leukocyte Recruitmentmentioning

confidence: 99%

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Villar¹,

Hobbs²,

Ahluwalia

2008

Journal of Endocrinology

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“…The loss of proper endothelial function is a hallmark of vascular diseases such as atherosclerosis, hypertension, blood clotting and inflammation [2][3][4][5]. The Krüppel-like factors (KLFs) are a family of zinc finger transcription factors with essential roles in cell growth, differentiation and tissue development [6].…”

Section: Introductionmentioning

confidence: 99%

FBW7 regulates endothelial functions by targeting KLF2 for ubiquitination and degradation

Wang

Liu

et al. 2013

Cell Res

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F-box and WD repeat domain-containing 7 (FBW7), the substrate-binding subunit of E3 ubiquitin ligase SCF FBW7 (a complex of SKP1, cullin-1 and FBW7), plays important roles in various physiological and pathological processes. Although FBW7 is required for vascular development, its function in the endothelium remains to be investigated. In this study, we show that FBW7 is an important regulator of endothelial functions, including angiogenesis, leukocyte adhesion and the endothelial barrier integrity. Using RNA interference, we found that the depletion of FBW7 markedly impairs angiogenesis in vitro and in vivo. We identified the zinc finger transcription factor Krüppel-like factor 2 (KLF2) as a physiological target of FBW7 in endothelial cells. Knockdown of FBW7 expression resulted in the accumulation of endogenous KLF2 protein in endothelial cells. FBW7-mediated KLF2 destruction was shown to depend on the phosphorylation of KLF2 via glycogen synthase kinase-3 (GSK3) at two conserved phosphodegrons. Mutating these phosphodegron motifs abolished the FBW7-mediated degradation and ubiquitination of KLF2. The siRNAmediated knockdown of FBW7 showed that KLF2 is an essential target of FBW7 in the regulation of endothelial functions. Moreover, FBW7-mediated KLF2 degradation was shown to be critical for angiogenesis in teratomas and in zebrafish development. Taken together, our study suggests a role for FBW7 in the processes of endothelial cell migration, angiogenesis, inflammation and barrier integrity, and provides novel insights into the regulation of KLF2 stability in vivo.

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“…Thus, while both anti and proinflammatory mechanisms are modulators of the vascular response to injurious challenges, their imbalance may result in vascular inflammation progressing to vascular dysfunction and culminating in CVD (reviewed in ref. 1).…”

Section: Introductionmentioning

confidence: 99%

Estrogen is a modulator of vascular inflammation

2008

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SummaryVascular inflammation underlies the pathogenesis of atherosclerosis. Atherosclerotic changes in the vasculature lead to conditions such as coronary artery disease and stroke, which are the major causes of morbidity and mortality worldwide. Epidemiological studies in premenopausal women suggest a beneficial role for estrogen in preventing vascular inflammation and consequent atherosclerosis. However, the benefits of estrogen are absent or even reversed in older postmenopausal subjects. The modulation of inflammation by estrogen under different conditions might explain this discrepancy. Estrogen exerts its antiinflammatory effects on the vasculature through different mechanisms such as direct antioxidant effect, generation of nitric oxide, prevention of apoptosis in vascular cells and suppression of cytokines and the renin-angiotensin system. On the other hand, estrogen also elicits proinflammatory changes under certain conditions, which are less completely understood. Some of the mechanisms underlying a possible proinflammatory role for estrogen include increased expression of the proinflammatory receptor for advanced glycation end products, increased tyrosine nitration of cellular proteins, and generation of reactive oxygen species through an uncoupled eNOS. In this review, we have presented evidence for both antiinflammatory and proinflammatory pathways modulated by estrogen and how interactions among such pathways might determine the effects of estrogen on the vascular system. IUBMBIUBMB Life, 60(6): 376-382, 2008

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Endothelial-Dependent Mechanisms of Leukocyte Recruitment to the Vascular Wall

Cited by 355 publications

References 125 publications

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

FBW7 regulates endothelial functions by targeting KLF2 for ubiquitination and degradation

Estrogen is a modulator of vascular inflammation

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