Cytochrome P450 and Vascular Homeostasis

Fleming, Ingrid

doi:10.1161/hh2101.099268

Cited by 386Eicosanoids and Hypertension PharmacologyInflammatory mediators and NSAID effectsNitric Oxide and Endothelin Effects

Cytochrome P450 and Vascular Homeostasis

Fleming, Ingrid·2001·Circulation Research

DOI 10.1161/hh2101.099268

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Abstract

Since the initial reports that renal cytochrome P450 (CYP) enzymes can metabolize arachidonic acid to substances which affect arterial tone, it has become increasingly clear that CYP enzymes expressed within the cardiovascular system play a crucial role in the modulation of vascular homeostasis. There is strong evidence suggesting that the activation of a CYP epoxygenase in endothelial cells is an essential step in nitric oxide and prostacyclin-independent vasodilatation of several vascular beds, particularly in the heart and kidney. A smooth muscle CYP ω-hydroxylase, on the other hand, generates a vasoconstrictor eicosanoid that is central to the myogenic response. Moreover, CYP epoxygenase and ω-hydroxylase products, as well as CYP-derived reactive oxygen species, are intracellular signal transduction molecules involved in several signaling cascades affecting numerous cellular processes, including vascular cell proliferation and angiogenesis. This review summarizes the vascular effects of epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid, both of which are CYP-derived metabolites of arachidonic acid, endogenously generated within endothelial and vascular smooth muscle cells. Although the link between CYP expression/activity and cardiovascular disease is currently tentative, the evidence being accumulated to suggest that CYP pathways are altered in animal models of hypertension and atherosclerosis can no longer be ignored. The development of selective pharmacological tools is, however, a prerequisite for the analysis of the involvement of specific CYP isoforms in the regulation of vascular homeostasis in human subjects.

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The presence of CYPOR and CYP proteins in endothelial cells makes them a significant source of superoxide in the vasculature.
“The presence of these proteins in endothelial cells makes them a significant source of superoxide in the vasculature (295, 298).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [295]

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Research works printed but not linked: 4

Zhang Y, Oltman CL, Lu T, Lee HC, Dellsperger KC, VanRollins M. EET homologues potently dilate coronary microvessels and activate BK Ca channels. Am J Physiol Heart Circ Physiol. 2001;280: H2430 -H2440.
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Alvarez J, Montero M, García-Sancho J. Cytochrome P450 may link intracellular Ca 2ϩ stores with plasma membrane Ca 2ϩ influx. Biochem J. 1991;274:193-197.
Fisslthaler B, Hinsch N, Chataigneau T, Popp R, Kiss L, Busse R, Fleming I. Nifedipine increases cytochrome P4502C expression and EDHF-mediated responses in coronary arteries. Hypertension. 2000;36: 270 -275.

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Authors: Fleming, I.
Affiliations: Goethe University Frankfurt (DE)
Corresponding author: Fleming, Ingrid
ORCID: Fleming, Ingrid
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2001-10-26
Volume: 89
Issue: 9
Pages: 753-762
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/hh2101.099268
OpenAlex: W2168349092
Cited by: 383
References: 142
Citations by year: 2026: 4 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 8 · 2019: 13 · 2018: 11 · 2017: 15 · 2016: 11 · 2015: 11 · 2014: 21 · 2013: 8 · 2012: 13
FWCI: 2.56
Type: journal article
Language: en
Open access: closed
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft (SFB 553)
Servier
Institut de Recherches Servier
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords: cytochrome P450, vascular homeostasis, arachidonic acid metabolism, epoxyeicosatrienoic acids, 20-hydroxyeicosatetraenoic acid, endothelial cells, vascular smooth muscle cells, vasodilation, vasoconstriction, myogenic response, reactive oxygen species, signal transduction, angiogenesis, hypertension, atherosclerosis, cardiovascular disease
MeSH terms: Animals, Biological Factors, Cardiovascular System, Cytochrome P-450 Enzyme System, Endothelium, Vascular, Epoxy Compounds, Free Radicals, Homeostasis, Humans, Hydroxyeicosatetraenoic Acids, Mixed Function Oxygenases, Isoenzymes, Muscle, Smooth, Vascular, Vasomotor System, 8,11,14-Eicosatrienoic Acid, Arachidonic Acid, Cytochrome P-450 CYP4A

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Cytochrome P450 and Vascular Homeostasis

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