Role of a disintegrin and metalloprotease with thrombospondin type 1 motifs in aged rat myocardium after ischemic preconditioning
10.3760/cma.j.issn.0254-9026.2011.01.015
- VernacularTitle:Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶在老年大鼠心肌缺血预适应中的作用
- Author:
Yong WANG
;
Congxin HUANG
;
Jinsong CHENG
;
Yifeng ZHOU
;
Hui WANG
;
Wenjing WU
;
Wenqiang LIAO
;
Jianyan WEN
;
Yuannan KE
;
Jingang ZHENG
- Publication Type:Journal Article
- Keywords:
Metalloproteases;
Myocardial reperfusion;
RNA,small interfering
- From:
Chinese Journal of Geriatrics
2011;30(1):54-58
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of ischemic preconditioning (IPC) on the expression of a disintegrin and metalloprotease with thrombospondin type 1 motifs (ADAMTS-1), and to study whether the application of small interfering (si)RNA specifically targeting ADAMTS-1 would help to recover IPC protection in the aged heart. Methods The 32 young (4 months) and 32 aged(24 months) male Sprague-Dawley (SD) rats were assigned randomly to IPC group (n=20) and sham operated group (n= 12) respectively. Myocardial samples from the ischemic-reperfused region were harvested for detecting the ADAMTS-1 expression. In addition, the 110 aged SD rats were assignedrandomly to ADAMTS-1 siRNA group and control group (n=55, each). The effects of ADAMTS-1siRNA transfcction on the expression of ADAMTS-1 protein, myocardial infarction survival rate,heart function and myocardial infarction size after IPC were observed.Results Twenty-four hours after IPC, the ADAMTS-1 protein expression increased significantly in iscbemic-reperfused region both in young and aged rats (P＜0. 05), and the protein expression was higher in aged rats than in young rats (P＜0.05). In young-IPC group, the absorbency showed ADAMTS-1 protein expression at 0 hrs and 24 hrs after IPC were 0. 05±0.01 and 0.12±0.03 by immunohistochemical staining, and were 0.68±0. 16 and 1. 17±0.21 by Western blots respectively. In aged-IPC group, the absorbency showed ADAMTS-1 protein expression at 0 hrs and 24 hrs after IPC were 0.07±0. 03 and 0.21 ±0.04 by immunohistochemical staining, and were 0. 76±0. 21 and 1. 48±0. 17 by Western blots. In the aged rats, ADAMTS-1 siRNA transfection inhibited ADAMTS-1 protein expression (0. 66±0. 19and 0.78±0.21, by Western blots at 0 hrs and 24 hrs after IPC, P＞0.05), but didn't improve myocardial infarction survival rates [ADAMTS-1 siRNA group and sham operated group: 14.3% (5/35) vs. 17.1 %(6/35), P＞0.05], left ventricular fractional shortening [(14.0±3.2)% vs. (13.0±2.9)%, P＞0.05] and myocardial infarction size[(39.0±4.1)% vs. (38.0±5.3)%, P＞0.05].Conclusions ADAMTS-1 expression induced by IPC increases significantly in aged versus in young rats. ADAMTS-1 knockdown by siRNA inhibits ADAMTS-1 protein expression but cannot recover the age-associated loss of IPC protection.
