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Hyperphosphatemia, the elevated level of inorganic phosphate (Pi) in serum, is associated with increased cardiovascular morbidities and mortality. The effects of high Pi on endothelial cells are not well studied. This study investigated high Pi-induced endothelial cell apoptosis and the role of microRNA-21. Mouse myocardial endothelial cells (MEC) were cultured in normal (1 mM) and high (5 mM) Pi conditions. Apoptosis was detected by TUNEL staining and flow cytometry. MicroRNA profiles of MEC response to changes in Pi concentration were obtained using gene expression arrays. Expression levels of the microRNA-21 target genes, programmed cell death gene 4 ( PDCD4), poly(ADP-ribose) polymerase ( PARP), and phosphatase and tensin homolog ( PTEN), as well as NF-κB were measured by Western blotting and RT-PCR. MicroRNA-21-specific inhibitors and mimics were used to study effects of microRNA-21 on MEC apoptosis and gene expression regulations. High Pi induced MEC apoptosis and upregulated microRNA-21 expression. MicroRNA-21-specific mimics reproduced high Pi-induced apoptosis in normal Pi medium, and microRNA-21 inhibitors ameliorated the high Pi induction of apoptosis, suggesting that microRNA-21 mediated high Pi-induced MEC apoptosis. The microRNA-21 targets PDCD4, PTEN, PARP, and NF-κB were significantly downregulated in high Pi conditions. High Pi-induced downregulation of PDCD4 was abolished by microRNA-21 inhibitors and selective ERK inhibitor (selumetinib) and was reproduced by microRNA-21 mimics. Inhibitors and mimics of microRNA-21 did not have effects on high Pi-induced NF-κB downregulation. Selumetinib blocked high Pi-induced NF-κB downregulation. MicroRNA-21 mediates high Pi-induced endothelial cell apoptosis, which involves an ERK1/2/microRNA-21/PDCD4 pathway. High Pi-induced downregulation of NF-κB expression is mediated by an ERK1/2 signaling-dependent but microRNA-21-independent mechanism. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) affects essentially all organ systems. Myocardial injury in TTP is often attributed to microthrombi formation. We present the first case report in the literature of an acute TTP patient with concomitant obstructive coronary artery disease (CAD) and acute myocardial infarction who underwent successful percutaneous coronary intervention (PCI). A 70-year-old female patient who was diagnosed with acute TTP required plasma exchange. The patient also experienced episodes of angina pectoris, elevated cardiac enzymes and global ST segment depressions on ECG. A subsequent non-invasive ischaemia workup revealed significant ischaemia. Coronary angiography revealed obstructive CAD in her right coronary artery, requiring PCI with a bare metal stent placement and dual antiplatelet therapy. The patient tolerated antiplatelet therapy well. At 6 months of follow-up, she had no recurrent angina. This case highlights the potential co-existence of obstructive CAD and acute TTP requiring careful differential diagnosis and treatment. [ABSTRACT FROM AUTHOR]

IMPORTANCE Reperfusion times for ST-elevation myocardial infarction (STEMI) occurring in outpatients have improved significantly, but quality improvement efforts have largely ignored STEMI occurring in hospitalized patients (inpatient-onset STEMI). OBJECTIVE To define the incidence and variables associated with treatment and outcomes of patients who develop STEMI during hospitalization for conditions other than acute coronary syndromes (ACS). DESIGN, SETTING, AND PARTICIPANTS Retrospective observational analysis of STEMIs occurring between 2008 and 2011 as identified in the California State Inpatient Database. EXPOSURES STEMIs were classified as inpatient onset or outpatient onset based on present-on-admission codes. Patients who had a STEMI after being hospitalized for ACS were excluded from the analysis. MAIN OUTCOMES AND MEASURES Regression models were used to evaluate associations among location of onset of STEMI, resource utilization, and outcomes. Adjustments were made for patient age, sex, comorbidities, and hospital characteristics. The analysis allowed for the location of inpatient STEMI to have a multiplicative rather than an additive effect for resource utilization since these measures were highly skewed. RESULTS A total of 62 021 STEMIs were identified in 303 hospitals, of which 3068 (4.9%) occurred in patients hospitalized for non-ACS indications. Patients with inpatient-onset STEMI were older (mean, 71.5 [SD, 13.5] years vs 64.9 [SD, 14.1] years; P < .001) and more frequently female (47.4%vs 32%; P < .001) than those with outpatient-onset STEMI. Patients with inpatient-onset STEMI had higher in-hospital mortality (33.6%vs 9.2%; adjusted odds ratio (AOR), 3.05; 95%CI, 2.76-3.38; P < .001), were less likely to be discharged home (33.7% vs 69.4%; AOR, 0.38; 95%CI, 0.34-0.42; P < .001), and were less likely to undergo cardiac catheterization (33.8% vs 77.8%; AOR, 0.19; 95%CI, 0.16-0.21; P < .001) or percutaneous coronary intervention (21.6%vs 65%; AOR, 0.23; 95%CI, 0.21-0.26; P < .001). Length of stay and inpatient charges were higher for inpatient-onset STEMI (mean length of stay, 13.4 days [95%CI, 12.8-14.0 days] vs 4.7 days [95%CI, 4.6-4.8 days]; adjusted multiplicative effect, 2.51; 95%CI, 2.35-2.69; P < .001; mean inpatient charges, $245 000 [95%CI, $235 300-$254 800] vs $129 000 [95%CI, $127 900-$130 100]; adjusted multiplicative effect, 2.09; 95%CI, 1.93-2.28; P < .001). [ABSTRACT FROM AUTHOR]