The CYP/20-HETE/GPR75 axis in hypertension

Froogh, Ghezal; García, Víctor; Schwartzman, Michal Laniado

doi:10.1016/bs.apha.2022.02.003

Cited by 9 publications

(4 citation statements)

References 132 publications

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“…142,143 Studies in animals and humans demonstrated that deficient 20-HETE biosynthesis in tubules and increased 20-HETE levels in the vasculature contribute to hypertension by sensitizing the vasculature to constriction-inducing stimuli, potentiating vascular inflammation, and causing endothelial dysfunction. 142,144,145 Another study of vascular calcification in mice demonstrated that the levels of multiple metabolites of AA were significantly increased in calcified aortas; the abundant metabolites included 12-HETE, 11-HETE, and 15-HETE, of which the most abundant metabolite was 12-HETE. A specific inhibitor of the metabolic enzyme arachidonic 15-LOX (ALOX15) significantly reduced the plasma 12-HETE level, promoted calcium deposition in the aortic arch and increased the calcium level in blood vessels.…”

Section: 41mentioning

confidence: 99%

Arachidonic acid metabolism in health and disease

Zhang,

Liu,

Sun

et al. 2023

MedComm

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Arachidonic acid (AA), an n‐6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers. These eicosanoids are generally considered proinflammatory molecules, as they can trigger oxidative stress and stimulate the immune response. Therefore, interventions in AA metabolic pathways are effective ways to manage inflammatory‐related diseases in the clinic. Currently, inhibitors targeting enzymes related to AA metabolic pathways are an important area of drug discovery. Moreover, many advances have also been made in clinical studies of AA metabolic inhibitors in combination with chemotherapy and immunotherapy. Herein, we review the discovery of AA and focus on AA metabolism in relation to health and diseases. Furthermore, inhibitors targeting AA metabolism are summarized, and potential clinical applications are discussed.

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Section: 41mentioning

confidence: 99%

Arachidonic acid metabolism in health and disease

Zhang,

Liu,

Sun

et al. 2023

MedComm

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“…In this study, participants with CYP3A4*1G genetic mutation had a 1-fold to 2-fold increase in the incidence of cardiac diseases than participants without genetic mutation. Recent researches have shown that certain CYP450 enzymes contribute to cardiovascular diseases [46][47][48]. Alcohol consumption is related to increased risk of coronary artery disease, alcoholic cardiomyopathy, atrial and ventricular dysrhythmias, and hypertension, while high consumption or binge drinking significantly increases the risk [49].…”

Section: Plos Onementioning

confidence: 99%

Cyp3A4 *1G polymorphism is associated with alcohol drinking: A 5-year retrospective single centered population-based study in China

Jia,

Zhang,

Zhou

et al. 2023

PLoS ONE

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Introduction We investigated the epidemiology of Cytochrome P450 (CYP) 3A4 genotype and the relationship between CYP3A4 genotype and alcohol drinking habits. Materials and methods A single-centered retrospective study was conducted on 630 patients who underwent CYP3A4*1G genetic testing. Their relevant information on epidemiology and etiology was collected. Laboratory testing, including CYP3A4*1G genotype, liver function tests, and serum lipid measurements were performed. Bi-variate logistic regressions were used to examine the relationship between variables. The relationship between alcohol drinking and CYP3A4*1G genotype was estimated. Demographic and clinical features were analyzed. Participants with drinking history were divided into non-heavy drinking and heavy drinking groups. Liver function and dyslipidemia of participants with drinking histories were compared between CYP3A4*1G mutation (GA+AA) and wild-type (GG) groups. Results Participants with CYP3A4*1G mutation(GA+AA) had an increased adjusted odds ratio (AOR) of 2.56 (95% CI, 1.4–4.65; P = 0.00) for alcohol abuse when compared with participants without CYP3A4 mutation (GG). In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury levels and serum lipid levels between CYP3A4*1G mutant and wild-type groups. Patients with CYP3A4*1G mutation had an increased AOR of cardiac-vascular diseases and malignant diseases compared with patients without CYP3A4*1G mutation. The epidemiology had no difference between GA and AA group. Conclusion The study indicated that there was association between alcohol drinking and CYP3A4*1G genetic mutation. In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury and dyslipidemia between CYP3A4*1G mutant and wild-type groups. CYP3A4*1G mutation was also related to cardiac-vascular diseases and malignant diseases.

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“…The metabolites of arachidonic acid (AA) endodermal hyperpolarized factor (EDHF) catalyzed by CYP2C gene subfamily are the most important causes of vascular endothelial relaxation [15], while EDHF acts as a vasodilator in all blood vessels including coronary arteries [16]. And these metabolites are thought to be a modulator of vascular tone, regulator of renal function, as well as factors in the occurrence and development of hypertension and cardiovascular disease [17]. In addition, reactive oxygen species (ROS) are produced in coronary endothelial cells during the reaction catalyzed by CYP2C, which can inhibit the vascular relaxation mediated by nitric oxide (NO) [18].…”

Section: Introductionmentioning

confidence: 99%

CYP2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a case-control study

Cai

et al. 2023

BMC Cardiovasc Disord

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Background Genetic factors have a certain proportion in the risk factors of hypertension. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with hypertension in Hakka population. Methods The study included 1,872 hypertensive patients and 1,110 controls. The genotypes of CYP2C19 rs4244285 and rs4986893 of all individuals were detected and analyzed. Results The genotype and allele distributions of CYP2C19 rs4244285 were significantly different between hypertension group and control group. The CYP2C19 *1/*1 genotype was the most predominant among the subjects (40.8%), followed by the CYP2C19 *1/*2 genotype (40.5%). The percentage of CYP2C19*1, *2, and *3 allele was 64.2%, 30.8%, and 5.0%, respectively. The proportion of intermediate metabolizers (IM) (49.3% vs. 42.9%), poor metabolizers (PM) (14.3% vs. 8.9%) (P < 0.001), and CYP2C19*2 allele (33.8% vs. 25.7%, P < 0.001) in hypertension group was significantly higher than that in control group. Multivariate logistic regression (adjusted for gender, age, smoking, and drinking) indicated that CYP2C19 *1/*2, *1/*3, and *2/*2 genotypes may increase susceptibility to hypertension. And the CYP2C19 IM genotype (IM vs. EM: OR 1.514, 95% CI: 1.291–1.775, P < 0.001), PM genotype (PM vs. EM: OR 2.120, 95% CI: 1.638–2.743, P < 0.001), IM + PM genotypes (IM + PM vs. EM: OR 1.617, 95% CI: 1.390–1.882, P < 0.001) may increase risk of hypertension. Conclusions CYP2C19 loss-of-function (IM, PM genotypes) is independent risk factor for hypertension susceptibility. Specifically, the risk genotypes include CYP2C19 *1/*2, *1/*3, and *2/*2.

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The CYP/20-HETE/GPR75 axis in hypertension

Cited by 9 publications

References 132 publications

Arachidonic acid metabolism in health and disease

Arachidonic acid metabolism in health and disease

Cyp3A4 *1G polymorphism is associated with alcohol drinking: A 5-year retrospective single centered population-based study in China

CYP2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a case-control study

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