PPARγ Agonist Ameliorates the Impaired Fluidity of the Myocardial Cell Membrane and Cardiac Injury in Hypercholesterolemic Rats

详细信息    查看全文

• 作者：Ye Wu ; Xiutao Tan ; Jue Tian ; Xin Liu ; Yehong Wang…
• 关键词：Cell membrane fluidity ; Cardiac injury ; Hypercholesterolemia ; Pioglitazone
• 刊名：Cardiovascular Toxicology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：17
• 期：1
• 页码：25-34
• 全文大小：
• 刊物主题：Pharmacology/Toxicology; Cardiology;
• 出版者：Springer US
• ISSN：1559-0259
• 卷排序：17

文摘

Hypercholesterolemia can increase the risk of cardiac injury, but the underlying mechanisms are not fully understood. The present study aimed to determine whether changes in the fluidity of the cardiomyocyte membrane may contribute to the increased susceptibility to myocardial ischemia/reperfusion (MI/R) injury observed in hypercholesterolemic rats. Male Wistar rats were fed a normal (n = 24) or high-cholesterol diet (n = 32) for 10 weeks. At the 6th week, the rats in the high-cholesterol diet group were treated with vehicle (n = 16, HC + V) or pioglitazone (n = 16, HC + PIO), a peroxisome proliferator-activated receptor-γ (PPARγ) agonist, and treatment lasted for the next 4 weeks. Rats in HC + V group displayed less membrane fluidity, a greater membrane cholesterol-to-phospholipid ratio (C/P), less Na+–K+-ATPase activity, and less cAMP content in their myocardial cells than rats fed a normal diet. A strong positive correlation was observed between membrane fluidity and cardiac injury, i.e., the myocardial infarct size when subjected to MI/R (30 min/24 h). Treatment with PIO restored much of the lost hypercholesterolemia-induced myocardial cell membrane fluidity, decreased membrane C/P ratio, increased Na+–K+-ATPase activity and cardiac cell cAMP content, improved cardiac function, and reduced the sizes of myocardial infarcts. Results demonstrated that hypercholesterolemia-induced decreased myocardial cell membrane fluidity may contribute to the increased susceptibility to cardiac injury, and PPARγ agonists may have therapeutic value in patients with hypercholesterolemia.