The Expression of Genes CYP1A1, CYP1B1, and CYP2J3 in Distinct Regions of the Heart and Its Possible Contribution to the Development of Hypertension.

IF 3.9 3区工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomedicines Pub Date : 2024-10-17 DOI:10.3390/biomedicines12102374

Maria L Perepechaeva, Natalia A Stefanova, Alevtina Y Grishanova, Nataliya G Kolosova

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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 CYP1B1, CYP2J3, and CYP1A1 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.

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CYP1A1、CYP1B1 和 CYP2J3 基因在心脏不同区域的表达及其对高血压发病的可能贡献。

背景：细胞色素 P450（CYP）参与内源性多不饱和脂肪酸（PUFAs）的代谢转化（形成心脏保护或心脏毒性产物），其功能的改变被认为会影响与年龄相关的心血管疾病的发展，并降低某些心脏选择性药物的疗效。例如，CYP2J2 激活或 CYP1B1 抑制可防止抗癌药物对心血管的毒性。目前还不清楚，能够将花生四烯酸和ω-3 PUFAs代谢为血管舒张和血管收缩衍生物的 CYPs 是否在所有心脏区域都有表达：研究对象为血压升高的衰老加速 OXYS 大鼠、OXYSb 大鼠（血压正常的 OXYS 子品系）以及作为 "健康 "对照的 Wistar 大鼠。对 1 个月、3 个月和 12 个月大鼠的左右心室、左右心房和主动脉的 mRNA 水平进行了测定：结果：我们发现所有心脏区域都表达能代谢花生四烯酸和ω-3 PUFAs的CYPs，并发现不同心脏区域的基因CYP1B1、CYP2J3和CYP1A1的mRNA水平以及表达随年龄变化的时间过程都存在显著差异：我们注意到，这些 CYPs 在高血压 OXYS 大鼠、正常血压 OXYSb 大鼠和健康 Wistar 大鼠的心脏区域和主动脉中的表达水平存在差异，但没有发现任何与 OXYS 大鼠高血压状态相关的明确模式。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedicines Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

5.20

自引率

8.50%

发文量

2823

审稿时长

8 weeks

期刊介绍： Biomedicines (ISSN 2227-9059; CODEN: BIOMID) is an international, scientific, open access journal on biomedicines published quarterly online by MDPI.