Hypertension, cardiovascular risk and polymorphisms in genes controlling the cytochrome P450 pathway of arachidonic acid: A sex-specific relation?

Fava, Cristiano; Ricci, Marco; Melander, Olle; Minuz, Pietro

doi:10.1016/j.prostaglandins.2011.11.007

Cited by 52 publications

(42 citation statements)

References 107 publications

(116 reference statements)

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“…Ward et al (2008) found that the A allele was a risk factor for hypertension. The other study by Fava et al (2012) found that the A allele was a risk factor for IS. This difference may be due to differences in race, differences in methodology, or different patient selection criteria.…”

Section: Discussionmentioning

confidence: 90%

“…However, these genes have not been reported in all ethnicities. CYP4F2 is expressed in the liver, heart, lung, kidney, and white blood cells, and is involved in 20-hydroxy eicosane arachidonic acid (20-HETE) metabolism (Fava et al, 2012). 20-HETE in vivo has significant physiological effects and achieves vascular smooth muscle depolarization through blocking Ca 2+ activation and K + channels, resulting in strong vasoconstriction.…”

Section: Introductionmentioning

confidence: 99%

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CYP4F2 gene single nucleotide polymorphism is associated with ischemic stroke

Yuan¹,

Zhang²,

Huang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The objective of this study was to explore the relationship between CYP4F2 gene polymorphism and ischemic stroke (IS) in the Han Chinese population. We performed a case-control study to genotype four single nucleotide polymorphisms (SNPs) (rs2108622, rs3093100, rs3093105, rs3093135) in the CYF4F2 gene. The genotype and haplotype distributions were compared between the case and control groups. We found that the GG genotype of rs2108622 in the CYP4F2 gene was associated with risk of IS (P = 0.023). Haplotype analysis indicated that the GGGT haplotype comprising rs2108622-rs3093100-rs3093105-rs3093135 was associated with IS, which suggests that the GGGT haplotype may be a risk factor for IS (P = 0.012). CYP4F2 gene polymorphism might increase the risk of IS in the Chinese population.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

CYP4F2 gene single nucleotide polymorphism is associated with ischemic stroke

Yuan¹,

Zhang²,

Huang³

et al. 2015

Genet. Mol. Res.

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“…Several genome-wide association studies have linked the sequence variants of human CYP4A11, the homologs of rat CYP4A1 and CYP4A2, to the development of hypertension, stroke, and cerebral vascular disorders in human population studies (7,10,13,14,63), but the mechanisms remain to be determined. The present finding that the myogenic response in the cerebral circulation and autoregulation of CBF is impaired in SS rats due to a genetic deficiency in the formation of 20-HETE and is restored in our new CYP4A1 transgenic SS rats now fills the knowledge gap and provides investigators an important new model to study the mechanism by which genetic defects in the myogenic response can contribute to the development of small vessel disease and brain injury.…”

Section: Perspectives and Significancementioning

confidence: 99%

Impaired myogenic response and autoregulation of cerebral blood flow is rescued in CYP4A1 transgenic Dahl salt-sensitive rat

Fan

Geurts

Murphy

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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We have reported that a reduction in renal production of 20-HETE contributes to development of hypertension in Dahl salt-sensitive (SS) rats. The present study examined whether 20-HETE production is also reduced in the cerebral vasculature of SS rats and whether this impairs the myogenic response and autoregulation of cerebral blood flow (CBF). The production of 20-HETE, the myogenic response of middle cerebral arteries (MCA), and autoregulation of CBF were compared in SS, SS-5(BN) rats and a newly generated CYP4A1 transgenic rat. 20-HETE production was 6-fold higher in cerebral arteries of CYP4A1 and SS-5(BN) than in SS rats. The diameter of the MCA decreased to 70 ± 3% to 65 ± 6% in CYP4A1 and SS-5(BN) rats when pressure was increased from 40 to 140 mmHg. In contrast, the myogenic response of MCA isolated from SS rats did not constrict. Administration of a 20-HETE synthesis inhibitor, HET0016, abolished the myogenic response of MCA in CYP4A1 and SS-5(BN) rats but had no effect in SS rats. Autoregulation of CBF was impaired in SS rats compared with CYP4A1 and SS-5(BN) rats. Blood-brain barrier leakage was 5-fold higher in the brain of SS rats than in SS-5(BN) and SS.CYP4A1 rats. These findings indicate that a genetic deficiency in the formation of 20-HETE contributes to an impaired myogenic response in MCA and autoregulation of CBF in SS rats and this may contribute to vascular remodeling and cerebral injury following the onset of hypertension.

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“…CYP, cysteinatoheme mixed function mono-oxygenases enzymes, oxidizes AA into epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs), which are known to play an important role in the maintenance of cardiovascular health . CYP ω-hydroxylases, namely CYP4 family, metabolize AA into its cardiotoxic form 20-HETE, whereas Elshenawy et al 2013;Fava et al 2012;Gross et al 2005;Schwartzman et al 1996;Wu and Schwartzman 2011;Yousif et al 2009;Zordoky et al 2008 CYP epoxygenases, mainly CYP2B, CYP2C and CYP2J subfamilies, metabolize AA into four regioisomers of cardioprotective EETs,14,11,8,6-EET metabolites (Roman 2002). EETs are further metabolized by soluble epoxide hydrolase (sEH) into their corresponding degradation products dihydroxyeicosatrienoic acids (DHETs) (Imig et al 2002).…”

Section: Introductionmentioning

confidence: 99%

5-, 12- and 15-Hydroxyeicosatetraenoic acids induce cellular hypertrophy in the human ventricular cardiomyocyte, RL-14 cell line, through MAPK- and NF-κB-dependent mechanism

Maayah

El‐Kadi

2015

Arch Toxicol

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Recent studies have established the role of mid-chain hydroxyeicosatetraenoic acids (HETEs) in the development of cardiovascular disease. Mid-chain HETEs have been reported to have vasoconstrictive and pro-inflammatory effects. However, whether mid-chain HETEs can induce cardiac hypertrophy remains unclear. Therefore, the overall objective of the present study was to elucidate the potential hypertrophic effect of mid-chain HETEs in the human ventricular cardiomyocytes, RL-14 cells, and to explore the mechanisms involved. For this purpose, RL-14 cells were treated with increasing concentrations of mid-chain HETEs (2.5, 5, 10 and 20 µM). Thereafter, the cardiac hypertrophy markers and cell size were determined using real-time polymerase chain reaction and phase contrast imaging, respectively. Phosphorylated mitogen-activated protein kinase (MAPK) level and nuclear factor kappa B (NF-κB) binding activity were determined. Our results showed that mid-chain HETEs induced cellular hypertrophy in RL-14 cells as evidenced by the induction of cardiac hypertrophy markers, α- and β-myocin heavy chain and atrial and brain natriuretic peptide as well as the increase in cell size. Mechanistically, all mid-chain HETEs were able to induce the binding activity of NF-κB to its responsive element in a HETE-dependent manner, and they significantly induced the phosphorylation of ERK 1/2. The induction of cellular hypertrophy was associated with proportional increase in the formation of dihydroxyeicosatrienoic acids parallel to the increase of soluble epoxide hydrolase enzyme activity. In conclusion, our study provides the first evidence that mid-chain HETEs induce cellular hypertrophy in RL-14 cells through MAPK- and NF-κB-dependent mechanism.

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Hypertension, cardiovascular risk and polymorphisms in genes controlling the cytochrome P450 pathway of arachidonic acid: A sex-specific relation?

Cited by 52 publications

References 107 publications

CYP4F2 gene single nucleotide polymorphism is associated with ischemic stroke

CYP4F2 gene single nucleotide polymorphism is associated with ischemic stroke

Impaired myogenic response and autoregulation of cerebral blood flow is rescued in CYP4A1 transgenic Dahl salt-sensitive rat

5-, 12- and 15-Hydroxyeicosatetraenoic acids induce cellular hypertrophy in the human ventricular cardiomyocyte, RL-14 cell line, through MAPK- and NF-κB-dependent mechanism

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