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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-1β (IL1β), 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.

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.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.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 was100 mm Hg were responsive to drug therapy. Seven of eight patients with an asymmetric septal hypertrophy (ASH) ratio==1.3 and LVOT gradient100 mm Hg were responsive to drug therapy. Only 3 of 16 patients with an ASH ratio1.3 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.Our results demonstrate that drug therapy effectively reduces the LVOT gradient in patients with asymmetric septal hypertrophy and a less severe LVOT gradient.

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 μmol/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. (J Vasc Surg 2002;36:158-63.)

methods: A total of 1055 adults (mean age 63±13, 58.8% men) without diabetes mellitus, systolic dysfunction or other heart disease underwent a thorough physical examination including tissue Doppler echocardiography. We designated peak early mitral annular velocity (e’) of less than 5.0 to indicate 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 and evaluated results with regard to three age groups: young (≤ 49 yrs), middle-aged (50-69 yrs) and elderly (≥ 70 yrs) for both men and women.

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.

We studied the echocardiographic findings and clinical features of left ventricular pseudoaneurysm after mitral valve replacement. From December 1979 to March 1991, 1050 patients underwent mitral valve replacement at our institute, and eight patients (0.8%) had left ventricular pseudoaneurysm. In all eight patients, left ventricular pseudoaneurysm developed after the second mitral valve replacement. The incidence of left ventricular pseudoaneurysm among 253 patients who had had previous mitral valve surgery was 3.1%. Seven of the eight patients were still alive and were followed up from 5 to 136 months (mean, 57 months) after the development of left ventricular pseudoaneurysm; these patients had no complications. One patient died as a result of low cardiac output after mitral valve replacement in spite of repair of the left ventricular pseudoaneurysm. This patient had a long and wide myocardial laceration near the left ventricular pseudoaneurysm. In the other seven patients, transthoracic echocardiography demonstrated a large extraventricular cavity along the posterobasal left ventricle. In five of these patients, a turbulent flow in the neck of the left ventricular pseudoaneurysm was recorded both in systole and diastole by pulsed and color Doppler echocardiography. Transesophageal echocardiography clearly showed the narrow neck of the left ventricular pseudoaneurysm and an abnormal flow between the left ventricle and the left ventricular pseudoaneurysm. Generally, when left ventricular pseudoaneurysm develops after mitral valve replacement, surgical repair is the first choice of therapy. Our study demonstrated, however, that the development of left ventricular pseudoaneurysm was not always associated with a poor prognosis without surgical intervention.(ABSTRACT TRUNCATED AT 250 WORDS)