基因、和在心脏不同区域的表达及其对高血压发展的可能作用。
The Expression of Genes , , and in Distinct Regions of the Heart and Its Possible Contribution to the Development of Hypertension.
作者信息
Perepechaeva Maria L, Stefanova Natalia A, Grishanova Alevtina Y, Kolosova Nataliya G
机构信息
Institute of Molecular Biology and Biophysics, Federal Research Center for Fundamental and Translational Medicine, Timakova Str. 2, Novosibirsk 630060, Russia.
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Akad. Lavrentiev Ave., Novosibirsk 630090, Russia.
出版信息
Biomedicines. 2024 Oct 17;12(10):2374. doi: 10.3390/biomedicines12102374.
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.
背景
据信，参与内源性多不饱和脂肪酸（PUFAs）代谢转化（形成心脏保护或心脏毒性产物）的细胞色素P450（CYP）功能改变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抑制可预防抗癌药物的心血管毒性。目前尚不清楚能够将花生四烯酸和ω-3多不饱和脂肪酸代谢为血管舒张和血管收缩衍生物的细胞色素P450是否在所有心脏区域均有表达。
方法
实验以血压升高的衰老加速型OXYS大鼠、OXYSb大鼠（血压正常的OXYS亚系）和Wistar大鼠作为“健康”对照进行。测定了1个月、3个月和12个月大鼠的右心室、左心室、右心房、左心房和主动脉中的mRNA水平。
结果
我们发现所有心脏区域均表达能够代谢花生四烯酸和ω-3多不饱和脂肪酸的细胞色素P450，并揭示了心脏区域在基因、和的mRNA水平以及表达随年龄变化的时间进程方面存在显著差异。
结论
我们注意到，这些细胞色素P450在心脏区域和主动脉中的表达水平在高血压OXYS大鼠、血压正常的OXYSb大鼠和健康Wistar大鼠之间存在差异，但未发现与OXYS大鼠高血压状态相关的任何明确模式。
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