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A 74 year-old male with old anterior and inferior myocardial infarctions was treated with staged percutaneous coronary intervention. A chronic total occlusion of the middle segment of the left anterior descending branch was successfully stented during the first stage, and during the second stage, preprocedural intravascular ultrasonography (IVUS) revealed that the proximal segment of the right coronary artery was diffusely stenosed by mixed plaque. Directional coronary atherectomy under IVUS guidance was performed, but coronary slow flow appeared during the procedure. After successfully bailing out with intracoronary nicorandil, percutaneous thrombectomy and manual blood pumping, 2 coronary stents were implanted to fully cover the lesion. Quite contrary to expectation, the no-reflow phenomenon appeared just after post-dilatation and a repeat of the same maneuver could not completely recover coronary flow. Plaque fragility could not be predicted from the IVUS examination.

A 74 year-old male with old anterior and inferior myocardial infarctions was treated with staged percutaneous coronary intervention. A chronic total occlusion of the middle segment of the left anterior descending branch was successfully stented during the first stage, and during the second stage, preprocedural intravascular ultrasonography (IVUS) revealed that the proximal segment of the right coronary artery was diffusely stenosed by mixed plaque. Directional coronary atherectomy under IVUS guidance was performed, but coronary slow flow appeared during the procedure. After successfully bailing out with intracoronary nicorandil, percutaneous thrombectomy and manual blood pumping, 2 coronary stents were implanted to fully cover the lesion. Quite contrary to expectation, the no-reflow phenomenon appeared just after post-dilatation and a repeat of the same maneuver could not completely recover coronary flow. Plaque fragility could not be predicted from the IVUS examination.

Background Tissue factor (TF), expressed in endothelial cells (ECs) and enriched in human atherosclerotic lesions, acts as a critical initiator of blood coagulation in acute coronary syndrome. Basic fibroblast growth factor (bFGF) induces the proliferation and migration of ECs and plays a role in angiogenesis and restoration of endothelial integrity. As TF is implicated in angiogenesis, we studied the effect of bFGF on TF gene and protein expression. Methods: Human umbilical vein ECs (HUVECs) were exposed to bFGF. TF mRNA was assessed by Northern blot and TF protein was assessed by Western blot. TF promoter activity was assessed by transient transfection assay and transcription factor was identified by electro mobility shift assay. Results bFGF increased TF mRNA and protein expression in HUVECs. Increased TF mRNA was attenuated by inhibition of extracellular signal-regulated kinase kinase in human ECV304 cells. Transient transfection assays of the human TF promoter-luciferase construct (-786/+121 bp) demonstrated that bFGF induced transcription was dependent on the elements within the -197 to -176 bp relative to the transcription start site of the human TF gene. This region contains NF-κB like binding site. Electro mobility shift assay showed that bFGF increased nuclear translocation or DNA binding of NF-κB transcription factor to TF promoter. Nucleotide substitution to disrupt NF-κB like site reduced bFGF stimulated promoter activity. Fenofibric acid, an agonist ligand for the peroxisome proliferator activated receptor-α, reduced basal and bFGF stimulated TF expression. Conclusions These results indicate that bFGF may increase TF production in ECs through activation of transcription at NF-κB binding site, and control coagulation in vessel walls. Fibrate can inhibit TF expression and therefore reduce the thrombogenecity of human atherosclerotic lesions.

The effects of alpha 1-adrenergic stimulation on intracellular pH (pHi) and Ca2+ concentration ([Ca2+]i) were investigated in isolated rat cardiomyocytes with fluorescence dyes, BCECF and fura-2, respectively. In the presence of 5 or 25 mM HCO3- norepinephrine (NE) increased pHi in a dose-dependent manner. Intracellular alkalinization was inhibited by prazosin and phentolamine but not by yohimbine. NE-induced alkalinization was inhibited in the presence of a Na+/H+ exchange inhibitor (5-(N,N-hexamethylene) amiloride (HMA)), a C kinase inhibitor (H-7) or a calmodulin inhibitor (W-7), or in the absence of extracellular Na+. NE also increased [Ca2+]i following the pHi increase, which was abolished in the absence of extracellular Na+ or Ca2+. This Ca2+ influx was inhibited by HMA but not by diltiazem (10(-5) M). Thus, we conclude that alpha 1-adrenergic stimulation enhances Na+/H+ exchange by activation of C kinase, thereby allowing intracellular alkalinization, and that subsequent activation of Na+/Ca2+ exchange increases Ca2+ influx.

Objective: Osteopontin (OPN) is up-regulated in several experimental models of cardiac remodeling, but its direct effects remain unclear. We investigated the role of OPN in the development of cardiac fibrosis and remodeling using OPN-deficient mice. Moreover, we examined whether the inhibitory effect of eplerenone (Ep), a novel aldosterone receptor antagonist, against cardiac fibrosis and remodeling, was mediated through the inhibition of OPN expression in wild-type mice.Methods: Wild-type and OPN-deficient mice were treated with angiotensin II (AII) for 4 weeks. Wild-type mice receiving AII were divided into two groups, a control group and an Ep treatment group.Results: AII treatment significantly elevated blood pressure and caused cardiac hypertrophy and fibrosis in wild-type mice. Ep treatment and OPN-deficiency could reduce the AII-induced elevation of blood pressure and ameliorate the development of cardiac fibrosis, whereas only Ep treatment abolished the development of cardiac hypertrophy.Conclusions: These results suggest that OPN has a pivotal role in the development of AII-induced cardiac fibrosis and remodeling. Moreover, the effect of Ep on the prevention of cardiac fibrosis, but not cardiac hypertrophy, might be partially mediated through the inhibition of OPN expression.