Reduction of infarct size in the rat heart by LPS preconditioning is associated with expression of angiogenic growth factors and increased capillary density

Inflammation induces the expression of angiogenic growth factors in tissues , which leads to microvascular growth. Bacterial lipopolysaccharide (LPS) p rovokes a transient inflammatory response in the heart and induces delayed cardiac resistance to post-ischemic contractile dysfunction. In this study, we examined: 1) the effects of LPS on myocardial expression of basic fibro blast growth factor (bFGF) and vascular endothelial growth factor (VEGF), 2 ) whether an increase in the density of myocardial microvessels follows the expression of angiogenic growth factors, and 3) the effect of LPS on myoca rdial resistance to infarction and its relationship with microvascular grow th. Rats were treated with LPS (from Salmonella typhimurium, 0.5 mg/kg ip). The expression of bFGF and VEGF in the myocardium was examined at 6 and 12 h after LPS treatment by immunofluorescent staining. Myocardial capillary and arteriole densities were determined 3 days after LPS treatment by morph ometry, using immunofluorescent staining of von Willebrand factor (a marker protein of endothelial cells) and alpha-smooth muscle actin (a marker prot ein of smooth muscle cells). To examine cardiac resistance to infarction, h earts were subjected to 40 min of regional ischemia and 2 h of reperfusion by reversible occlusion of left coronary artery at 3 days after LPS treatme nt. LPS induced cardiac bFGF and VEGF at 6 and 12 h after treatment. The ex pression of these growth factors was followed by an increase in myocardial capillary density (2032 +/- 78/mm(2) vs. 1617 +/- 47/mm(2) in saline contro l, P < 0.05), but not arteriole density, at 3 days. Meanwhile, infarct size was significantly reduced by LPS preconditioning (infarct/left ventricle 1 2.3 +/- 1.04% vs. 21.7 +/- 1.65% in saline control, 43% reduction, P < 0.05 ). These results suggest that LPS preconditioning induces cardiac bFGF and VEGF, and an increase in myocardial capillary density. This increased myoca rdial capillary density is associated with a reduced infarct size after in vivo regional ischemia-reperfusion.