ADAMTS-1 expression in rat myocardium after ischemic preconditioning: age-associated differences.

Abstract

BACKGROUND:

It has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning.

METHODS:

Sixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated.

RESULTS:

ADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats.

CONCLUSIONS:

Cardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.

• Authors: Yong Wang, Cong-Xin Huang, Yi-Feng Zhou, Jin-Song Cheng, Hui Wang, Wen-Jing Wu, Wen-Qiang Liao, Jian-Yan Wen, Yuan-Nan Ke, Jin-Gang Zheng
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 124 Issue 1 Pg. 95-9 (Jan 2011) ISSN: 2542-5641 [Electronic] China
• PMID: 21362315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ADAM Proteins
• ADAMTS1 Protein
• Adamts1 protein, rat

Topics

• ADAM Proteins (metabolism)
• ADAMTS1 Protein
• Aging (metabolism, physiology)
• Animals
• Immunohistochemistry
• Ischemic Preconditioning, Myocardial
• Male
• Myocardial Infarction (metabolism, pathology)
• Myocardium (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley