Hyaluronan synthase 2 (HAS2) overexpression diminishes the procatabolic activity of chondrocytes by a mechanism independent of extracellular hyaluronan.

Osteoarthritis (OA) is a progressive degenerative disease of the joints caused in part by a change in the phenotype of resident chondrocytes within affected joints. This altered phenotype, often termed proinflammatory or procatabolic, features enhanced production of endoproteinases and matrix metallo-proteinases (MMPs) as well as secretion of endogenous inflammatory mediators. Degradation and reduced retention of the proteoglycan aggrecan is an early event in OA. Enhanced turnover of hyaluronan (HA) is closely associated with changes in aggrecan. Here, to determine whether experimentally increased HA production promotes aggrecan retention and generates a positive feedback response, we overexpressed HA synthase-2 (HAS2) in chondrocytes via an inducible adenovirus construct (HA synthase-2 viral overexpression; HAS2-OE). HAS2-OE incrementally increased high-molecular-mass HA >100-fold within the cell-associated and growth medium pools. More importantly, our results indicated that the HAS2-OE expression system inhibits MMP3, MMP13, and other markers of the procatabolic phenotype (such as TNF-stimulated gene 6 protein (TSG6)) and also enhances aggrecan retention. These markers were inhibited in OA-associated chondrocytes and in chondrocytes activated by interleukin-1ß (IL1ß), but also chondrocytes activated by lipopolysaccharide (LPS), tumor necrosis factor α (TNFα), or HA oligosaccharides. However, the enhanced extracellular HA resulting from HAS2-OE did not reduce the procatabolic phenotype of neighboring nontransduced chondrocytes as we had expected. Rather, HA-mediated inhibition of the phenotype occurred only in transduced cells. In addition, high HA biosynthesis rates, especially in transduced procatabolic chondrocytes, resulted in marked changes in chondrocyte dependence on glycolysis versus oxidative phosphorylation for their metabolic energy needs.

4-Methylumbelliferone Diminishes Catabolically Activated Articular Chondrocytes and Cartilage Explants via a Mechanism Independent of Hyaluronan Inhibition.

Depletion of the cartilage proteoglycan aggrecan is one of the earliest events that occurs in association with osteoarthritis. This loss is often accompanied by a coordinate loss in another glycosaminoglycan, hyaluronan. Chondrocytes experimentally depleted of cell-associated hyaluronan respond by switching to a pro-catabolic metabolism that includes enhanced production of endogenous inflammatory mediators and increased synthesis of matrix metalloproteinases. Hyaluronan turnover is also increased. Together, such a response provides for possible establishment of a self-perpetuating spiral of events that maintains or prolongs the pro-catabolic state. Chondrocytes or cartilage can also be activated by treatment with pro-inflammatory cytokines and mediators such as IL-1ß, TNFα, LPS, fibronectin fragments, and hyaluronan oligosaccharides. To determine the mechanism of chondrocyte activation due to hyaluronan loss, a depletion method was required that did not include degrading the hyaluronan. In recent years, several laboratories have used the coumarin derivative, 4-methylumbelliferone, as a potent inhibitor of hyaluronan biosynthesis, due in part to its ability to sequester intracellular UDP-glucuronic acid and inhibition of hyaluronan synthase transcription. However, contrary to our expectation, although 4-methylumbelliferone was indeed an inhibitor of hyaluronan biosynthesis, this depletion did not give rise to an activation of chondrocytes or cartilage. Rather, 4-methylumbelliferone directly and selectively blocked gene products associated with the pro-catabolic metabolic state of chondrocytes and did so through a mechanism preceding and independent of hyaluronan inhibition. These data suggest that 4-methylumbelliferone has additional useful applications to block pro-inflammatory cell activation events but complicates how it is used for defining functions related to hyaluronan.

Cancer antigen-125 plasma level as a biomarker of new-onset atrial fibrillation in postmenopausal women.

OBJECTIVE: Plasma cancer antigen (CA)-125 is a tumour marker recently shown to be associated with systolic heart failure and new-onset atrial fibrillation (AF) after myocardial infarction. However, no reports have described the relationship between CA-125 and new-onset AF in healthy postmenopausal women. The aim of the present study was to evaluate the relationship between CA-125 and new-onset AF in postmenopausal women. METHODS: Between 2005 and 2015, 2086 women, including 1012 postmenopausal women, visited our hospital for annual health check-ups. We excluded patients with systolic dysfunction, chronic inflammatory disease, chronic obstructive pulmonary disease, histories of AF or neoplastic diseases. A total of 746 postmenopausal women underwent thorough physical examinations, including those for biomarkers such as brain natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP) and CA-125. RESULTS: During the 10-year observation period, AF was documented in 31 participants (4.2%). The mean age of participants developing AF (75±6 years) was higher than that of those without AF (68±8 years). Participants developing AF showed significantly higher CA-125 (11.4±6.3 U/mL) and hs-CRP (0.10±0.11 mg/dL) levels than did those without AF (7.7±3.2 U/mL, p<0.01; 0.07±0.08 mg/dL, p<0.05). Cox regression analyses revealed ageing (HR 1.3; 95% CI 1.08 to 1.57; p<0.01) and plasma CA-125 levels (HR 1.29; 95% CI 1.10 to 1.51; p=0.02) as independent predictors of AF. CONCLUSIONS: High CA-125 levels might be associated with new-onset AF in healthy postmenopausal women.

Echocardiographic characteristics predicting efficacy of drug therapy in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: The efficacy of long-term drug therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM) remains unclear. This study was performed to characterize the echocardiographic findings of patients responsive to drug therapy. METHODS: Left ventricular outflow tract (LVOT) gradient and morphologic characteristics of the septum, posterior wall, and mitral valve were measured echocardiographically in 35 Japanese patients. The mean follow-up time was 41+/-22 months. RESULTS: Long-term drug therapy was effective in 14 patients and ineffective in 21 patients. Five of the refractory patients required mitral valve replacement to become free of symptoms. Only 5 of 21 patients whose LVOT gradient was 100 mm Hg were responsive to drug therapy, whereas 9 of 14 patients whose LVOT gradient was <100 mm Hg were responsive to drug therapy. Seven of eight patients with an asymmetric septal hypertrophy (ASH) ratio >==1.3 and LVOT gradient <100 mm Hg were responsive to drug therapy. Only 3 of 16 patients with an ASH ratio <1.3 were responsive to drug therapy. There was no correlation between the efficacy of drug therapy and the morphology of the mitral valve or the width of the LVOT. CONCLUSION: Our results demonstrate that drug therapy effectively reduces the LVOT gradient in patients with asymmetric septal hypertrophy and a less severe LVOT gradient.

Gender differences in predictors of left ventricular myocardial relaxation in non-obese, healthy individuals.

BACKGROUND: Previous studies indicate that individuals with metabolic syndrome (MetS) might be at risk for left ventricular (LV) diastolic dysfunction. However, little is known about which metabolic factors contribute to the development of LV dysfunction in individuals who are not obese or overweight and who do not have diabetes mellitus and/or cardiovascular disease. METHODS: Participants without diabetes mellitus, systolic dysfunction, or other heart diseases underwent a thorough physical examination, including tissue Doppler echocardiography. A peak early mitral annular velocity (e') of <5.0 was designated as indicating abnormal LV myocardial relaxation (LVMR). We performed single and multiple logistic regression analyses of e' and cardiovascular risk factors, including MetS factors and indicators of major organ dysfunction. Normal-weight subjects (body mass index <25 kg/m2) were also analyzed. RESULTS: A total of 1055 individuals (mean age, 63 ± 13 years) participated, of which 307 (29.1%) had MetS and 199 (18.9%) had abnormal LVMR. Multiple logistic regression analysis revealed waist circumference (WC) (odds ratio [OR] 1.04, P < 0.05) and age (OR 1.10, P < 0.05) to be predictors of abnormal LVMR. In normal-weight subjects (n = 806), aging (OR 1.08, P < 0.01), abnormal WC (OR 3.80, P < 0.01), and renal dysfunction (OR 2.14, P < 0.01) were predictors of abnormal LVMR. Among MetS factors, abnormal WC in men (OR 3.70, P < 0.01) and high diastolic blood pressure (DBP) in women (OR 4.00, P = 0.01) were related to abnormal LVMR.

Accessory mitral valve tissue causing severe left ventricular outflow tract obstruction in an adult.

Accessory mitral valve (AMV) is a rare cause of left ventricular outflow tract (LVOT) obstruction and is extremely rare in adults. We report a case of an older adult with an AMV that caused severe LVOT obstruction. A parachute-like piece of tissue (the AMV) protruding into the LVOT during systole was first detected in a 45-year-old woman by echocardiography. Because the pressure gradient and dyspnea gradually progressed, she finally underwent a successful operation for removal when she was 48 years old.

Echocardiographically evaluated site of attachment of atrial myxoma may predict recurrence.

We explore the association between the site of attachment of nonfamilial left atrial myxoma and it's recurrence. Forty-three (11 male and 32 female; mean age, 55.9±13.6 years) of 49 consecutive patients with nonfamilial left atrial myxoma who had been evaluated with preoperative echocardiography, X were available for postoperative follow-up with transthoracic echocardiography, transesophageal echocardiography, or both, for an average period of 85.2±54.2 months (range, 6.5 to 215.5 months). We compared preoperative clinical and echocardiographic features of recurrent and nonrecurrent myxomas. Three (7%) of the 43 cases of atrial myxoma recurred at the same site after 24.1±7.6 months. Involvement of the mitral valve annulus or mitral valve leaflet (3 vs 0,p<0.001) was observed in the recurrent myxomas, but the two groups did not differ significantly in any other clinical features, laboratory data, or echocardiographic features of the recurrent and nonrecurrent myxoma. Preoperative echocardiographic observation of involvement of the mitral valve annulus or mitral valve leaflet may predict recurrence after surgery. Regular follow-up echocardiography was useful in the early detection of recurrence.

Noninvasive prediction of angiographic spasm provocation using trans-thoracic Doppler echocardiography in patients with coronary spastic angina.

BACKGROUND: In the present study it was examined whether transthoracic Doppler echocardiography (TTDE) would be useful for noninvasive diagnosis of coronary spastic angina (CSA) by assessing coronary arterial tone in the morning. METHODS AND RESULTS: The study population comprised 21 CSA patients and 27 control subjects. All diagnoses were angiographically confirmed by provocation test using acetylcholine. Coronary flow velocity reserve (CFVR) was measured at the distal left anterior descending artery with a frequency of 5.0 MHz ultrasound at baseline and after sublingual administration of nitroglycerin (NTG). Coronary arterial tone was assessed by obtaining the change of CFVR induced by NTG administration (CFVR(NTG/Pre)). Basal CFVR tended to be lower in CSA patients (2.13+/-0.63, 2.71+/-0.67, respectively, p = 0.05). CFVR after NTG was significantly higher in CSA patients (3.91+/-1.10, 3.07+/-0.74, p = 0.003). The CFVR(NTG/Pre) was significantly higher in CSA patients than in the control subjects (1.90+/-0.49, 1.15+/-0.22, p < 0.0001). Using a cut-off value of 1.4 in CFVR(NTG/Pre), the sensitivity and specificity for the diagnosis of CSA were 91% and 90%, respectively. CONCLUSION: TTDE appeared to be useful for the noninvasive diagnosis of CSA by assessing the coronary arterial tone.

[Trend and contributing factors of in-hospital deaths in patients with infective endocarditis over the last twenty years].

OBJECTIVES: To evaluate the changes in the clinical background to infective endocarditis and identify the contributing factors to in-hospital deaths over the last 20 years. METHODS: Seventy-five patients (mean age 48.2 +/- 24.0 years) with infective endocarditis treated between January 1984 and December 2003 at our hospital were evaluated retrospectively. The patients were divided into two groups (first decade, n = 26 and second decade, n = 49). RESULTS: The infection route was unknown in 65% of the patients, but the oral route was the most common known route (16.0%). Congenital heart disease (24.0%)was the most common background disease, followed by valvular heart disease (22.7%), and post prosthetic valve replacement (22.7%). The mitral valve was most frequently infected(56.0%), followed by the aortic valve (34.7%). Multi-valve infection was present in 13.3% of the patients. Although the frequency of streptococcal endocarditis reduced, that of staphylococcal endocarditis increased in the second decade. The overall in-hospital mortality was 26.7%, but slightly improved in the second decade (34.6% vs 22.4%, p = 0.26). The overall in-hospital mortality was similar between the surgically treated group and the non-surgically treated group (25.0% vs 27.3%, NS). In the surgically treated group, in-hospital mortality was lower in the second decade than the first decade, but higher in the group treated for active infective endocarditis. Multivariate analysis found age > or = 51 years, renal insufficiency, neurological abnormality, and culture negative as predictors of in-hospital mortality. CONCLUSIONS: Rapid and appropriate primary medical treatment are important in the active phase of infective endocarditis. Age > or = 51 years was the strongest predictor of in-hospital infective endocarditis death.

[Follow-up study of diastolic paradoxical flow in the left ventricle with apical hypertrophic cardiomyopathy].

OBJECTIVES: Left ventricular apical asynergy and cardiovascular complications were evaluated in patients with apical hypertrophic cardiomyopathy, in whom apical diastolic paradoxical flow toward the base could be detected by Doppler color flow echocardiography. METHODS: Twenty-nine patients with apical hypertrophic cardiomyopathy were followed up with echocardiographic examinations for at least 5 years. They were divided into three groups: those who persistently exhibited paradoxical flow (Group A, n = 13), those in whom paradoxical flow developed during the follow-up period (Group B, n = 8), and those in whom paradoxical flow was not detected during the follow-up period (Group C, n = 8). Peak flow velocity and duration of paradoxical flow, the presence or absence of apical asynergy, and cardiovascular complications were evaluated. RESULTS: The mean follow-up period was 7.3 +/- 1.4 years. In Groups A and B, the apical wall motion deteriorated over time, whereas there was no asynergy change in Group C. Further, peak flow velocity and duration of paradoxical flow increased throughout the follow-up period in Groups A and B, and were correlated with the severity of apical asynergy. Ventricular tachycardia and cerebrovascular complications also occurred more often in patients with paradoxical flow. CONCLUSIONS: The presence of paradoxical flow was related to the severity of apical asynergy and cardiovascular complications, and may be an important marker for evaluating the clinical course of patients with apical hypertrophic cardiomyopathy.

Single administration of cerivastatin, an HMG-CoA reductase inhibitor, improves the coronary flow velocity reserve: a transthoracic Doppler echocardiography study.

HMG-CoA reductase inhibitors (statins) have been shown to improve the endothelial function by lowering lipids. Recent studies also suggest a direct impact of statins on the vascular wall. We assessed the rapid effect of cerivastatin on the coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). The coronary flow velocity from the distal left anterior descending artery was measured in 16 healthy subjects (all male, age 24-38 years) using a 5-MHz transducer, on the day before, just before, and 3 h after administering 0.3 mg of cerivastatin. Hyperemia was achieved by the intravenous administration of adenosine, and the CFVR was calculated as the radio of the mean diastolic hyperemic coronary flow velocity to the basal flow velocity. The serum lipid profile and high-sensitivity C-reactive protein (hsCRP) were measured. The CFVR following the single administration of cerivastatin increased from 2.93+/-0.58 to 3.91+/-0.86, P=0.003, and was significantly higher than the CFVR measured at the same time on the previous day (3.91+/-0.86 vs 3.37+/-0.48, P=0.009). Neither the serum lipid profile nor hsCRP exhibited a remarkable change after cerivastatin administration. We concluded that a single-dose administration of cerivastatin, an HMG-CoA reductase inhibitor, improves the coronary flow velocity reserve without modifying the serum lipid profile.

Non-invasive assessment of coronary arterial tone using trans-thoracic Doppler echocardiography.

BACKGROUND: As coronary flow velocity (CFV) is inversely related to the luminal size that exists for the myocardial bed, the elevated arterial tone can be assessed as the higher flow velocity in the epicardial artery. We examined the usefulness of transthoracic Doppler echocardiography (TTDE) for the assessment of coronary arterial tone. METHODS AND RESULTS: A total of 32 patients underwent TTDE and angiography. The luminal diameter (LD) in the left anterior descending artery (LAD) was measured by using quantitative coronary angiography before and after nitroglycerin (NTG) administration. The ratio of post NTG LD to the control (LD(NTG/Pre)) was assessed as a standard parameter of coronary arterial tone. We also measured CFV and CFV reserve (CFVR) at the LAD by TTDE. We evaluated the change of CFV (CFV(NTG/Pre)) and CFVR (CFVR(NTG/Pre)) following NTG administration. The LD increased from 1.98+/-0.46 to 2.51+/-0.34 mm (p<0.001), while the CFV decreased from 23.9+/-10.0 to 16.3+/-5.6 cm/s (p<0.03), and the CFVR increased from 2.39+/-0.65 to 3.56+/-1.12 (p<0.001). There were significant correlations between CFV(NTG/Pre) and LD(NTG/Pre) (p<0.0001, R2 = 0.532), and between the CFVR(NTG/Pre) and LD(NTG/Pre) (p<0.0001, R2 = 0.715). CONCLUSION: TTDE can assess the coronary arterial tone by measuring the responses of CFV and CFVR to NTG administration.

Characteristics of hypertrophic obstructive cardiomyopathy refractory to medical treatment and selection of surgical methods.

BACKGROUND AND AIM OF THE STUDY: Treatment for hypertrophic obstructive cardiomyopathy (HOCM) has been reported; however, there has been no report on the characteristics of medication-responsive and -refractory hypertrophic obstructive cardiomyopathy (HOCM). Using the classification of systolic anterior movement (SAM) which has been previously reported, we tried to identify the characteristics and use them to treat HOCM appropriately. METHODS: The clinical, echocardiographic, catheterization, and surgical data of 29 hospitalized patients with HOCM during 1980 to 1999 were analyzed retrospectively. We classified SAM in all patients by echocardiography. Nineteen patients improved with medical treatment (medical group), and 10 patients underwent surgical treatment because of ineffectiveness of medication (surgical group). We studied the relation between types of SAM and medical/surgical groups, and examined the relation between types of SAM and the surgical methods. RESULTS: Type I SAM was significantly more frequent in the medical group, while type II SAM was more frequent in the surgical group (p = 0.047). Patients in the surgical group underwent mitral valve replacement (MVR), myectomy, or a combination of MVR and myectomy. Left ventricular outflow gradient (LVOG) of over 100 mmHg was recognized in almost all patients with type II SAM. CONCLUSIONS: It was suggested that patients with medication-responsive HOCM tended to have type I SAM and those with refractory HOCM tended to have type II SAM. We consider that in type I SAM, if the position of the papillary muscles changed with medication or myectomy, shift of the chordae and type I SAM were reduced or disappeared. However, in type II SAM, even if the position of the papillary muscles changed, SAM did not disappear because lifting of the mitral leaflets remained. It is therefore suggested that patients with type II SAM should undergo at least MVR.

[Prosthetic valve endocarditis caused by Streptococcus constellatus infection complicated with perivalvular abscess: serial observation by transesophageal echocardiography: a case report].

A 61-year-old man was admitted to an associated hospital because of fever. He had undergone aortic valve and mitral valve replacement 6 years ago, because of rheumatic aortic valve stenosis, and mitral valve stenosis and regurgitation. He had prosthetic valve endocarditis caused by a rare Streptococcus constellatus infection complicated by multiple organ failure and systemic embolism. We considered that surgical treatment was difficult, and continued antibiotic treatment. The inflammatory reaction and fever improved. Prosthetic valve endocarditis is often difficult to identify and treat. Streptococcus constellatus infection is characterized by destruction and formation of abscess. We followed up the patient by transesophageal echocardiography, and observed the course of change of the paravalvular abscess around the aortic valve from echogenic to echolucent.

Extremely rapid formation of mitral valve ring abscess in infective endocarditis.

A patient with infective endocarditis (IE) due to methicillin-resistant staphylococcus aureus (MRSA) was found to have conversion of the hypoechoic region of the posterior mitral valve ring apparatus into a clearly delineated echolucent space by repeating transthoracic echocardiography at an interval of 1 week. Color Doppler showed features of blood entry into this space. Abscess formation in IE due to MRSA may be quick and repeated echocardiography may help detect the complications of IE. Semiurgent mitral valve plasty was performed for the associated prolapse of the posterior mitral leaflet using a hand-made, rolled, twisted autologous pericardial ring.

Hemodynamics during chronic amiodarone administration in Japanese patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia: a retrospective study.

OBJECTIVES: Nonischemic heart disease, especially idiopathic dilated cardiomyopathy, is relatively common among Japanese patients receiving amiodarone for concomitant ventricular arrhythmia, but the hemodynamic effects of amiodarone in these Japanese patients are unclear. The hemodynamic changes during chronic amiodarone administration were retrospectively studied in patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia. METHODS: Fifty-two patients [42 males, 10 females, 53 +/- 2 years (mean age +/- SE)] with ventricular tachyarrhythmia and idiopathic dilated cardiomyopathy with left ventricular ejection fraction of 27 +/- 1% (mean +/- SE) were treated with 200-400 mg daily of oral amiodarone as the loading dose for the initial 14 days and 100-200 mg daily maintenance dose for a further 6 months. No patients were taking beta-blockers or positive inotropic drugs. Echocardiographic examination was performed before (baseline), at week 2 and at month 6 of amiodarone therapy. Twenty four-hour Holter monitoring during the same time period was also performed in 34 patients. Seventeen patients underwent right heart catheterization before and at week 2. RESULTS: Echocardiographic measurements showed no significant change in left ventricular end-diastolic dimension, although there was a slight increase in fractional shortening from 16 +/- 1% to 19 +/- 1% (p < 0.05) and 18 +/- 1% (mean +/- SE) (p < 0.01) at week 2 and month 6 of amiodarone therapy, respectively. Amiodarone markedly reduced the mean heart rate and the frequency of premature ventricular complexes on ambulatory monitoring. The cardiac index did not change and the pulmonary capillary wedge pressure tended to decrease slightly at week 2 in the 17 patients who underwent catheterization. CONCLUSIONS: This retrospective study showed no worsening of the hemodynamic state during chronic amiodarone administration in Japanese patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia.

Direct in vivo evidence of a vascular statin: a single dose of cerivastatin rapidly increases vascular endothelial responsiveness in healthy normocholesterolaemic subjects.

AIMS: HMG-CoA reductase inhibitors (statins) have been demonstrated to have in vitro vascular effects. The aim of this study was to determine whether statins actually have in vivo vascular effects independent of their cholesterol-lowering effect. METHODS: We investigated the effect of a single dose of cerivastatin on vascular endothelial function by measuring flow-mediated dilatation of the brachial artery on ultrasound in 30 healthy volunteers with normal serum cholesterol concentrations. They were randomized to either placebo group (n = 15) or cerivastatin group (n = 15), and flow-mediated dilatation and endothelium-dependent dilatation were evaluated at before and 1 h, 3 h, 6 h, and 12 h after administration of placebo or cerivastatin. RESULTS: There were no differences in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde-LDL, and high-sensitivity C-reactive protein before and after administration of placebo or cerivastatin. Cerivastatin significantly increased flow-mediated dilatation at 3 h (P < 0.001), and this increase rapidly returned to the baseline level 6 h after administration. Endothelium--independent dilatation of brachial artery was not altered. CONCLUSIONS: A single dose of cerivastatin increased vascular endothelial responsiveness. Our data suggest that cerivastatin has a direct effect on the blood vessels that is independent of its lipid-lowering effect, and thus can be considered as a vascular statin.

Subepicardial aneurysm after anticoagulant therapy for a mural thrombus following anterior myocardial infarction.

A subepicardial aneurysm became evident in a male patient after anticoagulant therapy. On admission, it appeared to be an old anterior infarction accompanied by a mural thrombus. After warfarin administration, the thrombus disappeared and an echo-free space emerged outside the apical myocardial wall. The echo-free space communicated with the left ventricular cavity through the apical myocardial wall. Emergency surgery was undertaken and the patient survived. The aneurysm was covered with epicardium and there was an endomyocardial rupture of the muscle in the apical wall, which was the entrance of the aneurysm. This case suggests that cautious follow-up with echocardiography is necessary when anticoagulant therapy is selected for thrombi following myocardial infarction.

A 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, cerivastatin, suppresses production of matrix metalloproteinase-9 in human abdominal aortic aneurysm wall.

AIM: Abdominal aortic aneurysm (AAA) is a common vascular degenerative disease. AAA wall contains inflammatory cells that produce matrix metalloproteinases (MMPs) that probably contribute to elastolysis and remodeling of the aneurysm. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to reduce the expression of various molecules (including MMPs) independently of their cholesterol-lowering effect. The aims of this study are to investigate whether statins could modulate the biology of AAA wall and have a potential therapeutic value against AAAs. METHODS: We performed immunohistochemical analysis, evaluated MMP-9 production in the aortic wall from patients with infrarenal AAA (n = 10) and control patients with aortoiliac occlusive disease (n = 8), and examined the effect of cerivastatin on MMP-9 production in the AAA wall with organ culture. RESULTS: Neutrophils and macrophages were the cellular sources of MMP-9 in the AAA wall. The tissue concentrations of both total and active MMP-9 were significantly higher in tissues from AAA walls than in control aortic walls. Cerivastatin (0.001 to 0.1 micromol/L) significantly reduced the tissue levels of both total and active MMP-9 in a concentration-dependent manner (P <.001), and the production of tissue inhibitor of MMP-1 was unaffected. Cerivastatin neither reduced the number of infiltrating neutrophils and macrophages nor enhanced apoptosis of those cells, as evaluated with terminal transferase-mediated deoxyurisine triphosphate nick end labeling. CONCLUSION: These results suggest that cerivastatin can directly modulate the biology of the AAA wall and suppress MMP-9 production in the AAA wall by inhibiting the activation of neutrophils and macrophages, indicating that statin therapy could be useful for the prevention or treatment of AAA.

Current characteristics of infective endocarditis in Japan: an analysis of 848 cases in 2000 and 2001.

The Japanese Circulation Society appointed a committee to develop guidelines for the prevention, diagnosis and management of infective endocarditis in Japan. In making such guidelines, the committee required information on the current clinical characteristics of infective endocarditis and therefore performed a nationwide questionnaire survey of cases from 2000 and 2001. In total, data were received for 848 cases from 277 of the 817 hospitals surveyed. Mean age was 55+/-18 years and most patients were aged in their 50 s or 60 s; 53.9% of the patients had infective endocarditis of unknown origin (without any prior predisposing conditions or procedures) and the second most common etiology was post dental procedures. The most common microorganism was Gram-positive cocci (345 streptococci and 221 staphylococci) and methicillin resistant Staphylococcus aureus (MRSA) was found in 7.3%. Although more than 90% of cases with Streptococcus viridans were sensitive to penicillin G, 6.6% were resistant. All MRSAs were sensitive to vancomycin. The information obtained from the survey assisted in the making of the guidelines, which should become an indispensable tool for all clinicians.