Abstract 5614: In vivo Angiogenic and Anti-Apoptotic Signaling of Trx1 Against Acute Myocardial Infarction: An Insight With Transgenic Mice Overexpressing Trx1
Oxidative stress & alterations in thioredoxin-1 (Trx1) expression/activity & its interactions with several other proteins play a crucial role in cardiovascular complications after acute myocardial infarction (MI). Apart from its antioxidative capacity, Trx1 is known to possess antiapoptotic, growth stimulatory & angiogenic properties by modulating the expression/activity of its protein interacting partners thereby modifying the cell’s response to oxidative stress. However, the exact mechanism of the cardioprotective effect of overexpressing Trx1 has not been elucidated in acute MI. Therefore in the present study we have explored the angiogenic & cardioprotective potential of transgenic overexpression of Trx1 in mice in vivo MI model. The wild type (W) & the Trx1 transgenic (Tg+/+) mice were randomized into 4 groups:
Wild type Sham (WS),
Tg+/+ Sham (TS)
Tg+/+ MI (TMI).
MI was induced by permanent occlusion of LAD coronary artery. Sham groups underwent the same time matched surgical procedure without LAD ligation. We observed significant, reduction in infarct size (49±2vs35±2% infarct size/area at risk) & increase in capillary (2483±112vs3012±178) & arteriolar (15±0.9vs27±1) density (counts/mm2) with a consequent improvement in the myocardial functional parameters such as decreased LVIDs (3±0.2vs2.8±0.2) & increased ejection fraction (40. ±3vs53±3), & fractional shortening (19±2vs27±1) as assessed by echocardiography in the TMI compared to WMI. Immunoblot analysis revealed increased expression of Trx1 (6.2 fold), angiogenic VEGF (1.7 fold), anti-apoptotic survivin (2.4 fold) & Bcl2 (3.2 fold) in the TMI compared to WMI. Our study also identifies the potential of Trx1 overexpression in inducing angiogenesis probably via VEGF, reducing cell death & ventricular remodeling & a possible novel treatment strategy where Trx1 overexpression might alleviate oxidative stress & related human heart failure in several pathological conditions. The results obtained & the proteins identified in our current study may prove to be potential therapeutic targets in the treatment of ischemic heart diseases.