Fujun Shang

Serum omentin-1 levels are inversely associated with the presence and severity of coronary artery disease in patients with metabolic syndrome

Context: Omentin-1, an adipokine secreted from visceral adipose tissue, has been reported to be associated with coronary artery disease (CAD) and metabolic disorders. Objective: To clarify the relationship between serum omentin-1 levels and the presence and severity of CAD in patients with metabolic syndrome (MetS). Methods: We measured serum omentin-1 levels in 175 consecutive patients with MetS and in 46 controls. Results: Serum omentin-1 levels are inversely associated with the presence and angiographic severity of CAD in MetS patients. Conclusions: Serum omentin-1 might be a potential biomarker to predict the development and progression of CAD in MetS patients.

Chymase induces profibrotic response via transforming growth factor-β1/Smad activation in rat cardiac fibroblasts

Mast cell-derived chymase is implicated in myocardial fibrosis (MF), but the underlying mechanism of intracellular signaling remains unclear. Transforming growth factor-β1 (TGF-β1) is identified as the most important profibrotic cytokine, and Smad proteins are essential, but not exclusive downstream components of TGF-β1 signaling. Moreover, novel evidence indicates that there is a cross talk between Smad and mitogen-activated protein kinase (MAPK) signaling cascade. We investigated whether chymase activated TGF-β1/Smad pathway and its potential role in MF by evaluating cardiac fibroblasts (CFs) proliferation and collagen synthesis in neonatal rats. MTT assay and 3H-Proline incorporation revealed that chymase induced CFs proliferation and collagen synthesis in a dose-dependent manner. RT-PCR and Western blot assay demonstrated that chymase not only increased TGF-β1 expression but also upregulated phosphorylated-Smad2/3 protein. Furthermore, pretreatment with TGF-β1 neutralizing antibody suppressed chymase-induced cell growth, collagen production, and Smad activation. In contrast, the blockade of angiotensin II receptor had no effects on chymase-induced production of TGF-β1 and profibrotic action. Additionally, the inhibition of MAPK signaling had no effect on Smad activation elicited by chymase. These results suggest that chymase can promote CFs proliferation and collagen synthesis via TGF-β1/Smad pathway rather than angiotensin II, which is implicated in the process of MF.

Simvastatin attenuates hypertrophic responses induced by cardiotrophin-1 via JAK–STAT pathway in cultured cardiomyocytes

AbstactCardiotrophin-1 (CT-1) is a cytokine involved in the growth and survival of cardiac cells via activation of the Janus activated kinase/signal transducer activator of transcription (JAK/STAT). Statins, 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have effects that extend beyond cholesterol reduction and inhibit vascular smooth muscle cell (VSMC) proliferation and cardiac hypertrophy. However, whether stains also can inhibitin vitromyocardial hypertrophy or not still remains elusive. The purpose of this study was to explore the effects of simvastatin on the hypertrophy of cultured rat cardiomyocytes induced by CT-1 and to investigate whether this effect was mediated via JAK–STAT signaling pathway.Methods and Results: Primary cardiomyocytes from 2-day-old (P2) rats were cultured, stimulated with CT-1, and treated with various concentration of simvastatin. Incorporation of [3H] leucine, reverse transcription-polymerase chain reaction and western blotting techniques were used to investigate cardiacmyocyte size, ANP mRNA and JAK–STAT protein expression. Simvastatin was proved, in a dose-independent manner, to decrease cardiacmyocytes size as well as protein synthesis, and inhibit ANP mRNA synthesis and JAK–STAT protein expression induced by CT-1 in cardiacmyocytes.Conclusion: These results suggest that simvastatin can ameliorate cardiacmyocytes hypertrophyin vitrovia JAK–STAT signaling pathways. The present study provides a novel understanding and alternative therapeutic strategy for cardiac hypertrophy

Involvement of reactive oxygen species and JNK in increased expression of MCP-1 and infiltration of inflammatory cells in pressure-overloaded rat hearts

Increasing evidence has shown that inflammation is involved in pressure overload-induced cardiac remodeling. Monocyte chemoattractant protein-1 (MCP-1) plays a pivotal role in the inflammatory process. However, the mechanisms underlying the upregulation of MCP-1 expression remain poorly understood. In the present study, we examined the hypothesis that an increased production of reactive oxygen species (ROS) mediates the upregulation of MCP-1. In a pressure-overloaded rat heart model with abdominal aortic coarctation (AC), superoxide dismutase-inhibitable cytochrome C reduction assay showed that ROS generation in the myocardium increased significantly at 1 week by 61% (n=8, P<0.01), peaked at 2 weeks and maintained these high levels for 4 weeks. The elevation of ROS was paralleled by the increased expression of MCP-1 and left ventricular remodeling (cardiac hypertrophy, perivascular and interstitial fibrosis). The oral administration of the antioxidant, N-acetylcysteine (NAC, 0.2 g/kg/day), for 2 or 4 weeks, significantly attenuated ROS production by 69 and 68%, respectively (n=8, P<0.01), as well as left ventricular remodeling. NAC treatment for 2 weeks also significantly reduced the MCP-1 mRNA and protein levels by 52 and 60%, respectively (n=4-8, both P<0.01), but had no effect on blood pressure. In the rats with AC at 2 weeks, when MCP-1 expression and inflammation changes were overt, immunoblotting with phospho-specific antibodies revealed that extracellular regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase, were activated. NAC administration attenuated JNK activation, but had no effect on ERK. Our results suggest that increased ROS production may play an important role in the increased expression of MCP-1 in pressure overload-induced cardiac remodeling. JNK is likely involved in the signaling pathway.

Caveolin-1 restoration by cholesterol enhances the inhibitory effect of simvastatin on arginine vasopressin-induced cardiac fibroblasts proliferation

Caveolin-1 (cav1) has been implicated in the regulation of cell growth, and its expression can be regulated by cellular cholesterol content. In this study, we examined the effect of manipulating cellular cholesterol content on cav1 expression and the proliferation of adult rat cardiac fibroblasts (CFs) in the presence of arginine vasopressin (AVP). We found that AVP concentration-dependently down-regulated the expression of cav1 protein. Cav1 antisense treatment enhanced the proliferatory effect of AVP. Simvastatin, a HMG-CoA reductase inhibitor, further down-regulated cav1 protein, whereas repleting cells with cholesterol increased cav1 protein and enhanced the anti-growth effect of simvastatin. Our results provide a novel finding that cholesterol restoration may confer an additional inhibitory effect over simvastatin on AVP-induced CFs proliferation through cholesterol–cav1 interaction.

Association of serum adropin with the presence of atrial fibrillation and atrial remodeling

Adropin, a newly identified regulatory protein encoded by Enho gene, suppressed tumor necrosis factor α‐induced THP1 monocyte adhesion to human umbilical vein endothelial cells. In addition, inflammation is demonstrated to be involved in the mechanism of atrial fibrillation (AF). Atrial remodeling is correlated with the persistence and progression of AF. Adropin is hypothesized to correlated with AF and atrial remodeling. This study aims to determine the correlation of serum adropin and the presence of AF and remodeling.