2001 Fiscal Year Final Research Report Summary
The pathophysiology of cardiac and vascular remodeling and gene therapy
| Project/Area Number |
12670684
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Osaka City University |
|---|
Principal Investigator |
YOSHIYAMA Minoru Graduate school of Medicine, Osaka City University Associate Professor, 大学院・医学研究科, 助教授 (30240956)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Junichi Graduate school of Medicine, Osaka City University Professor, 大学院・医学研究科, 教授 (60275245)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Keywords | Cardiac remodeling / vascular rimodeling / Echocardiogram / Gene therapy |
|---|
| Research Abstract |
Inhibition of the renin-angiotensin system has been shown to prevent left ventricular remodeling after myocardial infarction. However, the effect of angiotensin on the signal transduction pathway of left ventricular remodeling after myocardial infarction is as yet unknown. ACE inhibitor and ARB inhibited JNKs, NF-kappa B and AP-1 activities. Increased JNKs, AP-1, NF- kappa B, and Sp-1 DNA-binding activities were suppressed by both drugs in the infarcted region. Doppler-echocardiography showed that ACE inhibitor and ARB prevented the dilatation of left ventricular cavity at 14 days and improved diastolic filling pattern. JNKs, AP-1 and NF- kappa B activation in myocardial infarcted rats could be responsible for left ventricular remodeling after myocardial infarction and angiotensin may be related to the activation of these signals.
The activator protein 1 (AP-1) transcriptional complex, containing Jun and Fos proteins, is involved in regulating many cellular processes such as proliferation and differentiation. However, little is known about a direct relationship between AP -1 activities and cardiomyocyte hypertrophy. To elucidate the roles of myocardial AP-1 activities, dominant negative mutant of c-Jun (DNJun) was overexpressed in cultured rat neonatal ventricular myocytes by adenovirus vector to abrogate endogenous AP-1 activation. Both endothelin 1 and phenylephrine significantly enhanced AP-1 DNA binding Adenovirus carrying DNJun prevented the transcriptional activation of the AP -1 by ET and PE, using AP-1 reporter enzyme firefly luciferase assay. Moreover, DNJun prevented the increase in incorporation of (3)H -phenylalanine, cell size, and the mRNA expression of ANP and BNP by ET and PE. We provide the first evidence that DNJun inhibits cardiomyocyte hypertrophy through inhibition of AP-1 transcriptinal activity.
|
Research Products
(12 results)
-
-
-
-
-
-
-
-
-
-
-
[Publications] Ehara S, Ueda M, NarukoT, Haze K, Itoh A, Otsuka M, Komatsu R, Matsuo T, Itabe H, Tkano T, Tsukamoto Y, Yoshiyama M, Takeuchi K, Yoshikawa J, Becker AE.: "Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes"Circulation.. 103. 1955-1960 (2001)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yoshiyama M, Omura T, Takeuchi K, Kim S, Shimada K, Yamagishi H, Teragaki M, Akioka K, Iwao H, Yoshikawa J.: "Angiotensin blockade inhibits increased JNKs, AP-1 and NF- kappa B DNA- binding activities in myocardial infarcted rats"J Mol Cell Cardiol.. 33. 799-810 (2001)
Description
「研究成果報告書概要(欧文)」より
