Roles of innate immunity in genesis of heart failure

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The objectives of this study were to investigate roles of innate immunity in the genesis or progression of myocardial dysfunction. Particularly, we tried to elucidate expression and functional significance of toll-like receptors (TLRs) in cardiac myocytes.1. Molecular cloning and expression analysis of the chick TLR2: we have cloned a cDNA that is homologous to mammalian TLR2s in cultured ventricular myocytes from 10-day-old chick embryos (CEVMs). This cDNA has turned out to correspond to the chick TLR2 type 1 (Fukui, et al.). Total TLR2 expression was detected by Northern blotting in the 10-day-old chick hearts and CEVMs.2. Rat angiotenisn II (A-IO) infusion model: Sprague-Dawley rats were injected subcutaneously and continuously with A-LI to create a ventricular hypertrophy/failure model. Fetal gene reprogramming and alteration of Ca^<2+> were observed in the A-Il-infused rats.3. Rat monocrotaline (MCT) infusion model: MCT was also given subcutaneously and continuously to male rats to create pulmonary hypertension and right ventricular failure. Fetal gene reprogramming occurred in both the right and left ventricles, although some differences were observed, suggesting a role of ventricular interaction.4. Measurements of Ca^<2+> in cardiac myocytes: Ca^<2+> transient in cardiac myocytes was recorded with flou-3 or cameleon, which can be expressed specifically in sarcoplasmic reticulum.