Rosiglitazone and bezafibrate modulate gene expression in a rat model of non-alcoholic fatty liver disease--a historical prospective.

Background: Genetic factors implicated in the pathogenesis of non-alcoholic fatty liver disease are poorly understood. Our aim was to characterize three genes involved in a rat model of non-alcoholic fatty liver disease and investigate the effect of rosiglitazone and bezafibrate.

Method: Five rats were fed a chow diet (controls) and 18 a fructose-enriched diet (FED) for 5 weeks: 6 were administered rosiglitazone and 6 bezafibrate during the last 2 weeks and 6 were not treated at all.

Exercise training improves cardiac function and attenuates arrhythmia in CPVT mice.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal ventricular arrhythmia evoked by physical or emotional stress. Recessively inherited CPVT is caused by either missense or null-allele mutations in the cardiac calsequestrin (CASQ2) gene. It was suggested that defects in CASQ2 cause protein deficiency and impair Ca(2+) uptake to the sarcoplasmic reticulum and Ca(2+)-dependent inhibition of ryanodine channels, leading to diastolic Ca(2+) leak, after-depolarizations, and arrhythmia.

Ischemia and reperfusion liver injury is reduced in the absence of Toll-like receptor 4.

Background/aims: Toll-like receptor 4 (TLR4) is expressed on hepatic non-parenchymal cells and hepatocytes. Hepatic signaling through TLR4 is critical in the pathogenesis of ischemia reperfusion injury (IRI) and leads to the release of cytokines. The role of bone marrow-derived TLR4 in the early reperfusion stage is unclear.

Islet-1 gene delivery improves myocardial performance after experimental infarction.

Objective: The LIM-homeobox transcription factor Isl1 plays a crucial role during heart embryogenesis and later on gives rise to adult resident cardiac stem cells. In this study, we aimed to discover new extra cardiac populations of Isl1 stem cells. We then investigated endogenous Isl1 kinetics after myocardial infarction (MI), and the effect of intra-myocardial gene transfer of naked DNA encoding Isl1 on functional recovery after MI.

Anti-ischemic effects of multivalent dendrimeric A₃ adenosine receptor agonists in cultured cardiomyocytes and in the isolated rat heart.

Adenosine released during myocardial ischemia mediates cardioprotective preconditioning. Multivalent drugs covalently bound to nanocarriers may differ greatly in chemical and biological properties from the corresponding monomeric agents. Here, we conjugated chemically functionalized nucleosides to poly(amidoamine) (PAMAM) dendrimeric polymers and investigated their effects in rat primary cardiac cell cultures and in the isolated heart.

Cardiomyocyte Toll-like receptor 4 is involved in heart dysfunction following septic shock or myocardial ischemia.

Toll-like receptors are expressed in immune cells and cardiac muscle. We examined whether the cardiac Toll-like receptor 4 (TLR4) is involved in the acute myocardial dysfunction caused by septic shock and myocardial ischemia (MI). We used wild type mice (WT), TLR4 deficient (TLR4-ko) mice and chimeras that underwent myeloablative bone marrow transplantation to dissociate between TLR4 expression in the heart (TLR4-ko/WT) and the immunohematopoietic system (WT/TLR4-ko).

Adenosine A3 receptor-mediated cardioprotection against doxorubicin-induced mitochondrial damage.

Cardiotoxicity associated with doxorubicin (DOX) treatment limits the therapeutic efficiency of this drug against cancer. 2-Chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), a selective agonist of A(3) adenosine receptor (A(3)R), reduces DOX toxicity in newborn rat cultured cardiomyocytes. The study's aim was to determine whether the protection demonstrated by Cl-IB-MECA attenuates cardiac depression in vivo.

Increased glycogen stores due to gamma-AMPK overexpression protects against ischemia and reperfusion damage.

During ischemia, endogenous glycogen becomes the principal substrate for energy through glycolysis. Cardiac-specific manipulation of AMP-activated protein kinase (AMPK) by over-expression of its regulatory gamma-subunit induces glycogen storage. The aim of this study was to examine whether heart glycogen in transgenic mice overexpressing PRKAG2 may protect from ischemia and reperfusion injury.

Ex-vivo effect of roxithromycin on human and rat arterial vasoactivity.

Background: Prior studies have suggested that inflammation and possibly bacterial infections play a role in atherogenesis and in the clinical pathogenesis of cardiovascular diseases. Treatment with the macrolide antibiotics has been associated with improved outcome from cardiovascular disease, although the mechanism through which they exert their effects may be unrelated to their antibiotic properties. Drugs that exert a vasodilator effect on arteries have been associated with attenuated atherogenesis and improved outcome from cardiovascular disease.