Matrix metalloproteinase-2 stimulates collagen-I expression through phosphorylation of focal adhesion kinase in rat cardiac fibroblasts.

Collagen-I is thought to be the main component of the extracellular matrix in cardiac fibrosis, the accumulation of which occurs with excessive activation of matrix metalloproteinase-2 (MMP-2). MMP-2 degrades the extracellular matrix; however, the relative importance of MMP-2 to collagen-I synthesis in cardiac fibroblasts remains unclear. We investigated whether extracellular activation of MMP-2 regulates collagen-I synthesis and phosphorylation of focal adhesion kinase (FAK) in rat cardiac fibroblasts. Primary cultures of rat cardiac fibroblasts were incubated with purified active MMP-2 to determine whether extracellular MMP-2 affects collagen-I synthesis and FAK phosphorylation in cardiac fibroblasts. Exogenous MMP-2 significantly stimulated FAK (Tyr397) phosphorylation and induced collagen-I expression in a time-dependent manner. Simultaneous treatment with the FAK inhibitor PF573228 abolished exogenous MMP-2-enhanced FAK (Tyr397) phosphorylation and collagen-I expression. Cells were then stimulated with norepinephrine (NE) to investigate whether endogenous MMP-2 could also induce collagen-I expression through FAK (Tyr397) phosphorylation. NE-stimulated endogenous MMP-2 activation in conditioned medium was significantly attenuated by simultaneous treatment with the MMP inhibitor PD166793. Similarly, NE-induced FAK (Tyr397) phosphorylation and collagen-I expression were significantly inhibited by simultaneous treatment with PD166793 or PF573228. Furthermore, MMP-2 knockdown induced by small interfering RNA (siRNA) significantly abolished endogenous MMP-2 expression and activation. MMP-2 siRNA significantly abolished NE-induced FAK (Tyr397) phosphorylation and collagen-I expression. These findings suggest that the extracellular activation of MMP-2 accelerated collagen-I synthesis in rat cardiac fibroblasts and that FAK phosphorylation (Tyr397) plays a pivotal role in MMP-2-stimulated collagen-I synthesis.

Acute cardiac volume load-related changes in plasma atrial natriuretic peptide and N-terminal pro-B-type natriuretic peptide concentrations in healthy dogs.

Plasma atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) have been used for the diagnosis of heart disease. The aim of the study was to investigate differences in secretory responses of plasma ANP and N-terminal proBNP (NT-proBNP) concentrations related to acute changes in preload. Six dogs were anaesthetised and infused intravenously with Ringer's solution (90-100mL/kg/h) for 60 min. Thereafter, furosemide was administered and dogs were monitored for 60 min. Plasma ANP and NT-proBNP concentrations were determined by chemiluminescence enzyme immunoassay and enzyme immunoassay, respectively. Volume overload significantly increased plasma ANP and NT-proBNP concentrations (P<0.001); however, preload reduction significantly reduced plasma ANP concentrations (P<0.05) without concurrent changes in plasma NT-proBNP. Mean pulmonary capillary wedge pressures were strongly correlated with plasma ANP concentrations (r=0.53, P<0.001), but not plasma NT-proBNP. Thus, plasma ANP is a useful, non-invasive parameter for measuring rapid haemodynamic changes.

Psychiatric and psychological outcomes of Japanese living donors following liver transplantation.

This study indexed the mental status in six living donor liver transplantations (LDLT) performed at the Juntendo University Hospital between 2005 and 2007. The donors' preoperative and postoperative psychiatric and psychological status was assessed using the Profile of Mood States (POMS) and the State-Trait Anxiety Inventory (STAI). The present study found that the donors' POMS anger/hostile score decreased significantly following transplantation. In addition, the STAI score suggested that donors had little anxiety or depression following the operation. Although the present study was limited due to the small number of donors, the findings suggest that a successful operation stabilizes donor mentality. The studied donors will be reassessed for their mental and physical condition in the future.