Heme Oxygenase 1 Is Differentially Involved in Blood Flow–Dependent Arterial Remodeling

Freidja, Mohamed Lamine; Toutain, Bertrand; Caillon, Antoine; Desquiret, Valérie; Lambert, D K; Loufrani, Laurent; Procaccio, Vincent; Henrion, Didier

doi:10.1161/hypertensionaha.111.170266

Cited by 31 publications

(38 citation statements)

References 43 publications

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“…HMOX1 is regarded as an antioxidative and atheroprotective gene (Pechlaner et al 2015) and has been reported to be involved in hemodynamics-related arterial remodeling (Freidja et al 2011). Although HMOX1 was up-regulated in calcific valve samples, its down-regulation in aortic valve endothelial cells under disturbed blood flow conditions may still contribute to oxidation, inflammation and calcification.…”

Section: Modulementioning

confidence: 99%

Integrated Bioinformatics Analysis Predicts the Key Genes Involved in Aortic Valve Calcification: From Hemodynamic Changes to Extracellular Remodeling

Liu

Luo

Sun

et al. 2017

Tohoku J. Exp. Med.

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In our aging world, increasing numbers of people are suffering from calcific aortic valve disease (CAVD). In this study, we used integrated bioinformatics analysis to predict several key genes that are involved in the initiation and progression of CAVD. Expression profiles of 15 calcific and 14 normal human aortic valve samples were generated from two gene expression datasets (GSE12644 and GSE51472). Dataset GSE26953 from the human aortic valve fibrosa-derived endothelial cells cultured under laminar or oscillatory shear stress was also evaluated. Related R packages were used to process the data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for functional annotation. Hub genes were identified based on the protein-protein interaction network. CAVD-related gene modules were identified by Weighted Gene Co-expression Network Analysis (WGCNA). The predicted key genes were manually reviewed. In our present work, complex connections among mechano-response, oxidative stress, inflammation and extracellular remodeling pathways in the etiology of CAVD were revealed. The key genes, thus identified, encode a transcription factor KLF2 and phospholipid phosphatase 3 (PLPP3) that are involved in mechanoresponses; eNOS involved in oxidative stress; IL-8 involved in inflammation; and collagen triple helix repeat containing 1 (CTHRC1) and secretogranin II (SCG2) involved in extracellular remodeling. These gene products are predicted to play critical roles in CAVD development and progression. The present study provides valuable information for future research and drug development.

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Section: Modulementioning

confidence: 99%

Integrated Bioinformatics Analysis Predicts the Key Genes Involved in Aortic Valve Calcification: From Hemodynamic Changes to Extracellular Remodeling

Liu

Luo

Sun

et al. 2017

Tohoku J. Exp. Med.

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“…Flowmediated outward remodeling of resistance arteries involves a transient inflammatory response (1) and oxidative stress (2) that favors the formation of peroxinitrite, which then activates metalloproteinases and extracellular matrix digestion (2,8,14,16,19). The final step, leading to diameter enlargement, requires a dilator stimulus (17). Flow-mediated outward remodeling is also associated with a compensatory increase in wall mass (11,32) due to ANG II type 1 receptor activation of ERK1/2 (11).…”

mentioning

confidence: 99%

“…MMPs induce then a partial dissociation of the extracellular matrix (ECM). In the last step, vasodilator agents, such as NO produced by eNOS (14), PGI2 produced by cyclooxygenase (COX)-2 (3), and/or carbon monoxide (CO) produced by heme oxygenase (HO)-1 (17,18), increase arterial diameter until the normalization of wall shear stress (44). In parallel, activation of the ANG II type 1 receptor (AT1R) and of MAPK ERK1/2 allow a compensatory hypertrophy aiming at normalization of wall strain induced by the diameter expansion (11).…”

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confidence: 99%

Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries

Tarhouni

Freidja

Guihot³

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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tance arteries, a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 mo and more. As FMR depends on estrogens in 3-mo-old female rats, we hypothesized that it might be preserved in 12-mo-old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligation of the side arteries in 3-and 12-mo-old male and female rats. After 2 wk, high-flow (HF) and normal-flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross-sectional area increased in HF arteries compared with NF arteries in 3-mo-old male and female rats. In 12-mo-old rats, diameter increased only in female rats. Endothelial nitric oxide synthase expression and endothelium-mediated relaxation were higher in HF arteries than in NF arteries in all groups. ERK1/2 phosphorylation, NADPH oxidase subunit expression levels, and arterial contractility to KCl and to phenylephrine were greater in HF vessels than in NF vessels in 12-mo-old male rats only. Ovariectomy in 12-mo-old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-mo-old male rats and ovariectomized female rats with hydralazine, the antioxidant tempol, or the angiotensin II type 1 receptor blocker candesartan restored HF remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-mo-old female rats compared with age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats. microcirculation; remodeling; blood flow; shear stress; sex; aging; estrogen RESISTANCE ARTERIES control local blood flow to organs. They are able to adapt in response to changes in hemodynamic conditions, even in the adult. A chronic increase in blood flow (shear stress) in these vessels induces outward hypertrophic remodeling associated with increased endothelium [nitric oxide (NO)]-dependent dilation, as shown in male (2,5, 33) and female rats (37). Chronic increases in blood flow occur in physiological conditions such as growth, chronic exercise, or pregnancy as well as in ischemic disorders, where they contribute to collateral arteries growth (7, 36). Flowmediated outward remodeling of resistance arteries involves a transient inflammatory response (1) and oxidative stress (2) that favors the formation of peroxinitrite, which then activates metalloproteinases and extracellular matrix digestion (2,8,14,16,19). The final step, leading to diameter enlargement, requires a dilator stimulus (17). Flow-mediated outward remodeling is also associated with a compensatory increase in wall mass (11, 32) due to ANG II type 1 receptor activation of ERK1/2 (11).As shown in male rats, flow-mediated remodeling of mesenteric resistance arteries does not occur in male rats aged 12 mo (40) or 24 mo (15). Although no diameter enlargement occurred in arteries after increasing blood flow, endotheliummedia...

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“…Furthermore, an induction of HO-1 has been reported to increase CO levels during hypertension, which can aggravate oxidative stress and promote end-organ damage. Current literature supports a relationship between hypertension, induced oxidative stress and an activation in the heme oxygenase system (Botros et al 2007, Freidja et al 2011. Also, AngII induction of HO-1 leads to an increase in endogenous CO levels (Aizawa et al 2000, Li et al 2004, Quadri et al 2014).…”

Section: Introductionmentioning

confidence: 93%

“…Also, AngII induction of HO-1 leads to an increase in endogenous CO levels (Aizawa et al 2000, Li et al 2004, Quadri et al 2014). Therefore, the adverse effects of significant increases in endogenously formed CO levels could be mediated through an induction of the oxidative stress pathway and/or reduction in NO which has been reported to increase superoxide formation and could be associated with endorgan damage (Jadhav et al 2008, Freidja et al 2011). Thus, the regulation of vascular tone by CO appears to be concentration dependent, where substantial elevations of CO levels via an increase in HO activity, produces an inhibition of NOS and contributes to endothelial dysfunction in several models of hypertension (Ndisang et al 2002, Teran et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Regulation of heme oxygenase-1 induction during recurrent insulin induced hypoglycemia

Quadri¹,

Prathipati²,

Jackson³

et al. 2014

IJM

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Background: Recurrent insulin induced hypoglycemia (RIIH) is an unavoidable risk of conventional therapeutic management of insulin dependent diabetes mellitus and is a primary cause of impaired glucose counter regulation. Circulating angiotensin II (AngII) has been reported to be elevated in diabetic models, and is linked to the promotion of hypertension. Objective: The current study was performed to evaluate the hypothesis that chronic insulin injections and/or hypoglycemia promotes hypertension via an increase in AngII, which increases endogenous carbon monoxide (CO) through an induction in heme oxygenase (HO-1). Methods: Male Sprague Dawley rats (200 250g) were treated for 2 weeks with daily injections of 7U/kg insulin or diluent. On the 14th day, surgery was performed and rats were administered various doses of captopril (2mg/kg, 8mg/kg, and 12mg/kg) or vehicle. Following the dose evaluation, subsets of previously treated animals were treated with vehicle, DALA (80g/kg), Captopril (12mg/kg) or a combination of DALA (80g/kg) + CAP (12mg/kg). Results: A dose dependent decrease in blood pressure was observed during captopril treatment in RIIH hypertensive rats. However, there was no change in urine output among the treatment groups. Captopril and DALA+CAP treatments produced a reduction in blood pressure as compared to animals treated with DALA alone. Carboxyhemoglobin and AngII concentrations were also reduced in animals treated with captopril and DALA+CAP. In addition, HO-1 protein levels in heart and kidney were reduced when compared to DALA treated animals. Conclusion: These results demonstrate that RIIH promotes an increase in circulating AngII and hypertension via an induction in HO-1, which significantly increases endogenous CO levels. Keywords: Angiotensin II, Carbon Monoxide, Heme Oxygenase, Recurring Insulin-Induced Hypoglycemia (RIIH).

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Heme Oxygenase 1 Is Differentially Involved in Blood Flow–Dependent Arterial Remodeling

Cited by 31 publications

References 43 publications

Integrated Bioinformatics Analysis Predicts the Key Genes Involved in Aortic Valve Calcification: From Hemodynamic Changes to Extracellular Remodeling

Integrated Bioinformatics Analysis Predicts the Key Genes Involved in Aortic Valve Calcification: From Hemodynamic Changes to Extracellular Remodeling

Role of estrogens and age in flow-mediated outward remodeling of rat mesenteric resistance arteries

Regulation of heme oxygenase-1 induction during recurrent insulin induced hypoglycemia

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