Amelioration of cardiac function in chronic myocardial infarcted rats following administration of vector pcDNA3.1AM.
1. The present study was designed to examine the cardiovascular effects of intravenously administered pcDNA3.1AM, a recombinant non-virus vector carrying a rat adrenomedullin (AM) gene translation fragment, in rats with chronic cardiac dysfunction induced by ligation of the left descending coronary artery. 2. Haemodynamic parameters were recorded by intraventricular catheterization. In situ hybridization and polymerase chain reaction (PCR) were performed to identify the distribution of the introduced vector. The concentration of AM was determined by radioimmunoassay. 3. Progressive cardiac dysfunction was observed following coronary artery ligation, as indicated by a significant reduction in mean arterial pressure (MAP) and increases in both central venous pressure (CVP) and end-diastolic pressure of the left ventricle (LVEDP; P < 0.01). Administration of pcDNA3.1AM significantly attenuated the progressive cardiac dysfunction and lowered the elevated CVP and LVEDP. The introduced vector was widely distributed in different organs, including the lungs, kidney, heart, liver, spleen and brain. However, intense staining of pcDNA3.1 AM was observed in the lungs and kidneys. The introduced vector was localized mainly in the endothelial cells of blood vessels. Radioimmunoassay showed elevated levels of AM in the plasma and lung and heart after surgery, but there was no significant further increase in the concentration of AM after pcDNA3.1AM delivery. 4. The present study has provided some novel findings on the potential beneficial effects of AM gene delivery on chronic cardiac function in rats. Expression of AM by a non-virus vector may also have therapeutic value against cardiac dysfunction in vivo.
Wang
Xiao-Fang
XF
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Shao
Ying
Y
Chen
Shao-Wei
SW
Tian
De-Zhi
DZ
Huang
Guo-Ying
GY
Huang
Yu
Y
Yao
Tai
T
Lu
Li-Min
LM
D053607:Adrenomedullin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D000818:Animals; D001794:Blood Pressure; D002496:Central Venous Pressure; D002908:Chronic Disease; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007668:Kidney / Q000378:metabolism; D008026:Ligation; D008168:Lung / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D053607:Adrenomedullin