Expression And Activation Of Mapk Family Members Involved In Hypertensive Cardiac Remodeling

Objective We studied the role of important member of MAPK family member ERK1/2 and P38 in the process of hypertensive cardiac remodeling ,including different anatomical structures and different histological region of the same anatomical structure ,which further clarified the role of ERK1/2 and p38 in hypertensive cardiac remodeling, and explored the molecular mechanism of hypertensive cardiac remodeling from the cell signal transduction .Methods (1)30 Spontaneously Hypertensive Rats (SHR) were divided into three groups, which were 4-week-old group,16-week-old group,24- week-old group;(2) 30 Wistar-Kyoto rats as the control group with the normal blood pressure;(3) 20 Spontaneously Hypertensive Rats:PD98059 prevented SHR24 groups and SD203580 prevented SHR24 groups. Light microscope micrometer was used to measure remodeling changes of SHR4,16,24 with HE staining , Immunohistochemistry, Weatern blotting techniques methods were used to observe the expression of PCNA,ERK1/2,P38,P-ERK1/2,P- P38 of myocardial cells in different anatomical parts .Results 1. Either SHR or WKY ,the ratio of heart weight to body weight was significantly higher with increased week age . SHR24 was significantly higher than SHR4 (P <0.05), SHR16, 24 was significantly higher than WKY16,24(P <0.05). 2. SHR relative left ventricular wall thickness was significantly increased with increased week age, the inner and middle of left myocardium was obvious. SHR24 relative left ventricular wall was significantly higher than SHR4(P <0.05), The inner and middle of left myocardium thickness of PD98059 group and SD203580 group was significantly lower than SHR24 (P <0.05). 3 PCNA expression significantly decrease with increased week age(P <0.05), SHR16 was higher than WKY16 (P <0.05). Different parts with different PCNA expression. (3) Non-phosphorylated ERK1/2 with the same week in different rats, and between WKY and SHR was no significant difference. But the expression of left myocardium was significantly higher than the right myocardium(P <0.05). The expression of P-ERK1/2 in the left myocardium and the left side of septum was significantly higher with increased week age. The expression of SHR16,,24 was significantly higher than WKY16, 24(P<0.05).The expression of P-ERK1/2 of PD98059 group was significantly lower than SHR(P<0.05).(4)The expression of non-phosphorylated P38 of all observation groups was no significant difference. The expression of the inner layer of left myocardium was significantly higher than the left side of septum and right myocardium(P <0.05) . The expression of P-P38 of myocardial cell in the left myocardium was significantly higher with increased week age.SHR16, 24 was significantly higher than WKY16, 24 group (P <0.05).The expression of P-P38 of SD203580 group was significantly lower than SHR (P <0.05).7 There was an positive correlation between PCNA,ERK1/2 and P38 .Conclusion(1) The ratio of heart weight to body weight and relative left ventricular wall thickness of spontaneously hypertensive rats increased gradually with week-old. The relative thickness of interventricular septum and right ventricle, and the relative left and right heart chamber diameter did not change, leading to concentric remodeling and concentric hypertrophy. We found that after the use of ERK-specific inhibitor PD98059 and the P38-specific inhibitor SD203580 respectively, the relative left ventricular wall thickness can be significantly reduced,. and hypertensive cardiac remodeling can be slow down to some extent .(2)Myocardial cells proliferation getting lower and lower with increased week age. In the state of spontaneous hypertension of the rats, higher proliferative activity of myocardial cells may involved in hypertensive cardiac hypertrophy, myocardial cell phenotypes, ultimately lead to the occurrence of cardiac remodeling.(3)The activation but not by increasing the total protein of ERK1/2 participating the cardiac remodeling of hypertension, Different parts with different role of P-ERK1/2.(4) During the development of spontaneously hypertensive rats , the activation of P38 expression. participating myocardial cells hypertrophy, left ventricular hypertrophy and cardiac remodeling.(5) ERK1/2 and P38 may promote each other, and promote high expression of PCNA, induced myocardial cells hypertrophy, proliferation activity increased and leading to cardiac remodeling.