title: Effects of thrombin and thrombin receptor activation on cardiac function after acute myocardial infarction.
abstract: Thrombin and thrombin receptor activation impact cardiomyocyte contraction and ventricular remodeling. However, there is some controversy regarding their effects in cardiac function, especially in cardiac dysfunction after acute myocardial infarction (AMI). A rat AMI model was created by left coronary artery ligation (LCA). Cardiac functional parameters, including the maximum left ventricular (LV) systolic pressure (LVSPmax), LV end-diastolic pressure (LVEDP), and the rise and fall rates in LV pressure (dp/dt max and dp/dt min, respectively), were measured. Hirudin decreased cardiac function within 120 minutes after AMI, whereas treatment with thrombin receptor-activating peptide (TRAP) reversed this hirudin-induced decrease in cardiac function. The mRNA and protein expression levels of inositol 1,4,5-trisphosphate receptor (IP3R) subtypes in infarct area tissues were analyzed by reverse transcription-polymerase chain reaction and immunoreaction. Hirudin decreased the expression levels of IP3R-1, -2, and -3 in the infarct area for up to 40 minutes after AMI, whereas TRAP treatment reversed these hirudin-induced effects. Treatment with the IP3R antagonist 2-aminoethoxydiphenyl borate (2.5 mg/kg) eliminated the effect of TRAP on the hirudin-induced decrease in cardiac function after AMI. Finally, TRAP increased the maximum binding capacity of the three IP3R subtypes, but only enhanced the affinity of IP3R-2. Thrombin and thrombin receptor activation improved cardiac function after AMI by an IP3R-mediated pathway, probably through the IP3R-2 subtype.
authors.affiliation: Division of Cardiology, Xiangtan Central Hospital Xiangtan, China ; Division of Cardiology, Yuebei Remin Hospital Affiliated to Medical College of Shantou University Shaoguan, China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Gu
authors.affiliation: Cerebropathia Department, Gansu Province Hospital of TCM Lanzhou, Gansu, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Cardiology, The First Aaffiliated Hospital of Sun Yat-Sen University Guangzhou, China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, Tongji Hospital, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Jiangmen Central Hospital Jiangmen, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Cardiology, Xiangtan Central Hospital Xiangtan, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Division of Cardiology, Xiangtan Central Hospital Xiangtan, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Division of Cardiology, Xiangtan Central Hospital Xiangtan, China.
authors.forename: Lilong
authors.initials: L
authors.lastname: Tang
keywords: IP3 receptor; Thrombin; acute myocardial infarction; cardiac function; thrombin receptor