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Background— Left ventricular (LV) remodeling after myocardial infarction is associated with hypertrophy of surviving myocytes and represents a major process that leads to heart failure. One of the intrinsic histone acetyltransferases, p300, serves as a coactivator of hypertrophy-responsive transcriptional factors such as a cardiac zinc finger protein GATA-4 and is involved in its hypertrophic stimulus-induced acetylation and DNA binding. However, the role of p300-histone acetyltransferase activity in LV remodeling after myocardial infarction in vivo is unknown. Methods and Results— To solve this problem, we have generated transgenic mice overexpressing intact p300 or mutant p300 in the heart. As the result of its 2–amino acid substitution in the p300-histone acetyltransferase domain, this mutant lost its histone acetyltransferase activity and was unable to activate GATA-4–dependent transcription. The two kinds of transgenic mice and the wild-type mice were subjected to myocardial infarction or sham operation at the age of 12 weeks. Intact p300 transgenic mice showed significantly more progressive LV dilation and diminished systolic function after myocardial infarction than wild-type mice, whereas mutant p300 transgenic mice did not show this. Conclusions— These findings demonstrate that cardiac overexpression of p300 promotes LV remodeling after myocardial infarction in adult mice in vivo and that histone acetyltransferase activity of p300 is required for these processes.

Introduction: Due to improvements of catheter design and approach, catheterization-related cerebral infarctions are expected to decrease, whereas this may be counterbalanced by increased risk profile of patients who undergo catheterization. Aims: The aim of this study is to examine the prevalence and risk factors of symptomatic and asymptomatic catheterization-related cerebral infarctions in the contemporary era, using diffusion-weighted magnetic resonance imaging (MRI). Methods and Results: We retrospectively analyzed 84 patients who underwent 1237 diagnostic and interventional catheterization procedures conducted within 2010 and 2011 in our hospital and who obtained the MRI within 14 days after catheterization. Among these, 10 patients developed a neurological event underwent MRI for suspected cerebral infarction (group A), whereas 74 patients were asymptomatic and underwent MRI for various reasons (group B); 52% of patients for the assessment before coronary bypass or surgery of aortic valve, 19% for the systemic vascular assessment for atherosclerotic diseases, and 28% for other reasons. The MRI revealed a fresh cerebral infarction in 5 patients in group A and 22 patients (29.7%) in group B. In patients with infarct lesions, more number of catheters were used (p=0.01), the intravascular procedure was longer (mean ± SEM, 17.1 ± 1.7 minutes vs. 22.7 ± 2.4 minutes, p=0.06), and the mean age tended to be higher (mean ± SEM, 74.1 ± 1.67 vs. 70.4 ± 1.1, p=0.07). The features of infarction were as follows: 62.9% of patients had multiple lesions and relatively small lesions in asymptomatic patients compared to those in symptomatic patients. Conclusions: Symptomatic cerebral infarction occurred after 5 of 1237 (0.4%) procedures. However, the rate of asymptomatic catheterization-related cerebral infarctions detected using diffusion-weighted MRI remains high in high-risk patients or candidates for cardiac surgery, when the rate is compared to that reported by previous studies conducted around 10 years ago. More number of catheters used and longer procedure time were associated with cerebral infarction in present study and careful procedural planning is warranted.

Background: Increasing evidence suggests that N-terminal probrain natriuretic peptide (NT-proBNP) may be a more discerning marker for the detection and evluation of heart failure than BNP. However, fundamental mechanisms that contribute to the heart failure in aortic stenosis (AS) and ischemic heart disease (IHD) via NT-proBNP remain unclear. Objectives: The purpose of this study was to investigate whether NT-proBNP represents autocrine/paracrine factors and are accumulated in pericardial fluid (PF) in patients with AS and IHD. Methods: With an electrochemiluminescent immunoassay, we measured the concentrations of NT-proBNP in serum and pericardial fluid simultaneously in 48 patients undergoing aortic valve replacement and 101 patients undergoing coronary artery bypass grafting. We investigated the correlation of NT-proBNP levels in serum or PF with hemodynamic variables. Results: In patients with AS, the PF levels of NT-proBNP were markedly elevated compared with serum levels (10747±17619 pg/ml vs. 2828±7787 pg/ml, p=0.0054). In patients with IHD, the PF levels of NT-proBNP were markedly elevated compared with serum levels (7224±16345 pg/ml vs. 764±1199 pg/ml, p=0.0001). In AS, NT-proBNP levels in PF but not in serum had closer relations with left ventricular (LV) end-diastolic (r=0.338, p=0.0463) and systolic volume indexes (r=0.551, p=0.0005). In AS, NT-proBNP levels in PF but not in serum inversely correlated with LV ejection fraction (EF) (r=-0.510, p=0.0002). In IHD, NT-proBNP levels in PF but not in serum had closer relations with left ventricular (LV) end-diastolic (r=0.493, p Conclusion: Increased PF concentrations of NT-proBNP reflects the direct actions as a local mediator against cardiac pressure overload in AS patients and cardiac voume overload in IHD patients with left ventricular systolic dysfunction.

Background: The development of congestive heart failure (CHF) is associated with left ventricular (LV) remodeling. However, fundamental mechanisms that contribute to this remodeling process remain unclear. The matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have been demonstrated to play a significant role in tissue remodeling through a number of pathological processes. Objectives: The purpose of this study was to investigate whether MMPs and TIMPs represent autocrine/paracrine factors and are accumulated in pericardial fluid. We previously reported that active MMP-2 levels in pericardial fluid served as more sensitive and accurate indicators of LV remodeling than did active MMP-2 levels in plasma. Methods: We measured the concentrations of the enzyme (active MMP-9) in both plasma and pericardial fluid in 20 patients during coronary artery bypass graft surgery. Results: The active MMP-9 level was significantly higher in pericardial fluid than in plasma (4.68 ± 1.17 vs. 2.58 ± 0.29 ng/ml, p Conclusions: Active MMP-9 levels in pericardial fluid serve as more sensitive and accurate indicators of LV remodeling than did active MMP-9 levels in plasma. Thus, active form of MMP-9 may be also secreted from the heart into the pericardial space with the progression of CHF, and it may have a pathophysiologic role in LV remodeling process as an autocrine/paracrine factor.