Congestive heart failure in COX2 deficient rats

被引：15

作者：

Wan, Qiangyou ^{[1
]}

Kong, Deping ^{[2
,3
]}

Liu, Qian ^{[2
,3
]}

Guo, Shumin ^{[2
,3
]}

Wang, Chenchen ^{[4
]}

Zhao, Yan ^{[4
]}

Ke, Zun-Ji ^{[1
]}

Yu, Ying ^{[2
,3
]}

机构：

[1] Shanghai Univ Tradit Chinese Med, Acad Integrat Med, Shanghai 201203, Peoples R China

[2] Tianjin Med Univ, Dept Pharmacol, Sch Basic Med Sci, Minist Educ, Tianjin 300070, Peoples R China

[3] Tianjin Med Univ, Tianjin Key Lab Inflammatory Biol, Key Lab Immune Microenvironm & Dis, Minist Educ,Sch Basic Med Sci, Tianjin 300070, Peoples R China

[4] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Nutr & Hlth, Shanghai 200031, Peoples R China

来源：

SCIENCE CHINA-LIFE SCIENCES | 2021年 / 64卷 / 07期

基金：

中国国家自然科学基金;

关键词：

NSAID; cyclooxygenase; prostaglandin; heart failure; energy metabolism; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYCLOOXYGENASE-2; MICE; INFLAMMATION; ROFECOXIB; CELECOXIB; EXCHANGE; REVEALS;

D O I：

10.1007/s11427-020-1792-5

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG) formation by targeting cyclooxygenase (COX) 1 and 2. Long-term use of NSAIDs that selectively inhibit COX2 increases the risk for thrombotic events, cardiac failure, and hypertension. However, the underlying mechanisms remain unclear. In this study, COX1- and COX2-deficient rats were created via Cas9/RNA-mediated gene targeting. DNA genotyping and Western blot analysis confirmed successful generation of COX1(-/-)and COX2(-/-)rats. Adult COX1(-/-)rats grew normally, while more than 70% of COX2(-/-)rats after wean died within 2 months. Echocardiography showed markedly reduced left ventricular ejection fraction and fractional shortening in adult COX2(-/-)rats compared to those in wildtype (WT) controls. Histological analysis revealed accumulation of inflammatory cells and severe interstitial and perivascular fibrosis in COX2(-/-)cardiac tissues. Moreover, cardiac ATP and acetyl-CoA production was dramatically decreased in COX2(-/-)rats. Consistently, the expression of genes related to mitochondrial oxidation, such as those that encode for subunits of pyruvate dehydrogenase complex and acyl CoA dehydrogenases, were downregulated, while glycolytic hexokinase 1 (HK1) was upregulated in COX2(-/-)heart tissues. These observations indicate that COX2-deficient rats developed spontaneously heart failure, likely as a result of dysregulated cardiac energy metabolism.

引用

页码：1068 / 1076

页数：9

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