The Expression of Genes , , and in Distinct Regions of the Heart and Its Possible Contribution to the Development of Hypertension

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 Oct 26

PMID 39457686

Authors

Maria L Perepechaeva

Natalia A Stefanova

Alevtina Y Grishanova

Nataliya G Kolosova

Affiliations

Soon will be listed here.

Abstract

Background: It is believed that alterations in the functioning of the cytochrome P450 (CYP), which participates in metabolic transformations of endogenous polyunsaturated fatty acids (PUFAs) (with the formation of cardioprotective or cardiotoxic products), affects the development of age-related cardiovascular diseases and reduces the effectiveness of some cardioselective drugs. For example, CYP2J2 activation or CYP1B1 inhibition protects against the cardiovascular toxicity of anticancer drugs. It is currently unclear whether CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs to vasodilatory and vasoconstrictive derivatives are expressed in all heart regions.

Methods: The work was performed on senescence-accelerated OXYS rats featuring elevated blood pressure, OXYSb rats (an OXYS substrain with normal blood pressure), and Wistar rats as a "healthy" control. The mRNA level was determined in the right and left ventricles, the right and left atria, and the aorta of 1-, 3-, and 12-month-old rats.

Results: We showed that all heart regions express CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs and revealed significant differences between heart regions both in the mRNA level of genes , , and and in the time course of expression changes with age.

Conclusions: We noticed that expression levels of these CYPs in the heart regions and aorta differ between hypertensive OXYS rats, normotensive OXYSb rats, and healthy Wistar rats but could not detect any clear-cut patterns associated with the hypertensive status of OXYS rats.

References

Westphal C, Konkel A, Schunck W . Cytochrome p450 enzymes in the bioactivation of polyunsaturated Fatty acids and their role in cardiovascular disease. Adv Exp Med Biol. 2015; 851:151-87. DOI: 10.1007/978-3-319-16009-2_6. View

Schwarz D, Kisselev P, Ericksen S, Szklarz G, Chernogolov A, Honeck H . Arachidonic and eicosapentaenoic acid metabolism by human CYP1A1: highly stereoselective formation of 17(R),18(S)-epoxyeicosatetraenoic acid. Biochem Pharmacol. 2004; 67(8):1445-57. DOI: 10.1016/j.bcp.2003.12.023. View

Whelton P, Carey R, Aronow W, Casey Jr D, Collins K, Himmelfarb C . 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association.... Circulation. 2018; 138(17):e426-e483. DOI: 10.1161/CIR.0000000000000597. View

Igonina T, Ragaeva D, Tikhonova M, Petrova O, Herbeck Y, Rozhkova I . Neurodevelopment and behavior in neonatal OXYS rats with genetically determined accelerated senescence. Brain Res. 2017; 1681:75-84. DOI: 10.1016/j.brainres.2017.12.021. View

Malik K, Jennings B, Yaghini F, Sahan-Firat S, Song C, Estes A . Contribution of cytochrome P450 1B1 to hypertension and associated pathophysiology: a novel target for antihypertensive agents. Prostaglandins Other Lipid Mediat. 2012; 98(3-4):69-74. PMC: 3339277. DOI: 10.1016/j.prostaglandins.2011.12.003. View

Wallace J . Eicosanoids in the gastrointestinal tract. Br J Pharmacol. 2018; 176(8):1000-1008. PMC: 6451073. DOI: 10.1111/bph.14178. View

Xu X, Zhang X, Wang D . The roles of CYP450 epoxygenases and metabolites, epoxyeicosatrienoic acids, in cardiovascular and malignant diseases. Adv Drug Deliv Rev. 2011; 63(8):597-609. DOI: 10.1016/j.addr.2011.03.006. View

Calder P . Eicosanoids. Essays Biochem. 2020; 64(3):423-441. DOI: 10.1042/EBC20190083. View

Shoieb S, El-Sherbeni A, El-Kadi A . Subterminal hydroxyeicosatetraenoic acids: Crucial lipid mediators in normal physiology and disease states. Chem Biol Interact. 2018; 299:140-150. DOI: 10.1016/j.cbi.2018.12.004. View

10.

Xu X, Zhao C, Wang L, Tu L, Fang X, Zheng C . Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice. Diabetes. 2010; 59(4):997-1005. PMC: 2844847. DOI: 10.2337/db09-1241. View

11.

El-Sherbeni A, El-Kadi A . Alterations in cytochrome P450-derived arachidonic acid metabolism during pressure overload-induced cardiac hypertrophy. Biochem Pharmacol. 2013; 87(3):456-66. DOI: 10.1016/j.bcp.2013.11.015. View

12.

Capdevila J, Wang W . Role of cytochrome P450 epoxygenase in regulating renal membrane transport and hypertension. Curr Opin Nephrol Hypertens. 2013; 22(2):163-9. PMC: 3893099. DOI: 10.1097/MNH.0b013e32835d911e. View

13.

Liberale L, Montecucco F, Tardif J, Libby P, Camici G . Inflamm-ageing: the role of inflammation in age-dependent cardiovascular disease. Eur Heart J. 2020; 41(31):2974-2982. PMC: 7453832. DOI: 10.1093/eurheartj/ehz961. View

14.

Hussain T, Al-Attas O, Al-Daghri N, Mohammed A, De Rosas E, Ibrahim S . Induction of CYP1A1, CYP1A2, CYP1B1, increased oxidative stress and inflammation in the lung and liver tissues of rats exposed to incense smoke. Mol Cell Biochem. 2014; 391(1-2):127-36. DOI: 10.1007/s11010-014-1995-5. View

15.

Lund A, Goens M, Kanagy N, Walker M . Cardiac hypertrophy in aryl hydrocarbon receptor null mice is correlated with elevated angiotensin II, endothelin-1, and mean arterial blood pressure. Toxicol Appl Pharmacol. 2003; 193(2):177-87. DOI: 10.1016/j.taap.2003.08.008. View

16.

Kumar A, Behl T, Jamwal S, Kaur I, Sood A, Kumar P . Exploring the molecular approach of COX and LOX in Alzheimer's and Parkinson's disorder. Mol Biol Rep. 2020; 47(12):9895-9912. DOI: 10.1007/s11033-020-06033-x. View

17.

Muraleva N, Devyatkin V, Kolosova N . Phosphorylation of αB-crystallin in the myocardium: Analysis of relations with aging and cardiomyopathy. Exp Gerontol. 2017; 95:26-33. DOI: 10.1016/j.exger.2017.05.009. View

18.

Dubey R, Tofovic S, Jackson E . Cardiovascular pharmacology of estradiol metabolites. J Pharmacol Exp Ther. 2003; 308(2):403-9. DOI: 10.1124/jpet.103.058057. View

19.

Shi Z, He Z, Wang D . CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators. Molecules. 2022; 27(12). PMC: 9230517. DOI: 10.3390/molecules27123873. View

20.

Yamaguchi A, Botta E, Holinstat M . Eicosanoids in inflammation in the blood and the vessel. Front Pharmacol. 2022; 13:997403. PMC: 9551235. DOI: 10.3389/fphar.2022.997403. View