We wished to elucidate a potential role of the tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible molecule 14 (Fn14) axis in myocardial fibrosis. Stimulation of neonatal rat cardiac fibroblasts (CFs) with TWEAK could increase CFs numbers and collagen synthesis. Conversely, when CFs were pretreated with siRNA against Fn14, induction of cell proliferation and collagen synthesis by TWEAK were inhibited. Pretreatment with TWEAK on CFs induced activation of the nuclear factor-kappaB (NF-кB) pathway and subsequently increased the production of metalloproteinase-9 (MMP-9). Cell treatment with siRNA against Fn14 led to inhibition of the NF-кB pathway. Additionally, after stimulation of cell with ammonium pyrrolidine dithiocarbamate, cell proliferation and collagen synthesis induced by NF-кB and the upregulation of MMP-9 production were inhibited. The present study suggested that the TWEAK/Fn14 axis increased cell proliferation and collagen synthesis by activating the NF-кB pathway and increasing MMP-9 activity. This axis may be important for regulating myocardial fibrosis.

Increased plasma osteoprotegerin levels are associated with the presence and severity of acute coronary syndrome.

No abstract

Objective: To examine whether aortic valve sclerosis (AVS) detected by transthoracic echocardiography (TTE) has a high association with coronary arteriosclerosis. Methods: Clinical and angiographic features and TTE findings were retrospectively analyzed in a blinded fashion for 138 consecutive patients, of whom 58 had AVS and 80 had non-AVS diseases. Both histological and immunohistochemical studies were performed on frozen aortic valve sections obtained at autopsy from 7 AVS and 3 non-AVS patients. Results: AVS and coronary artery disease (CAD) had similar clinical risk factors. The AVS group had a higher positive rate of coronary angiography and a higher incidence rate of multivessel CAD than the non-AVS group. The sensitivity, specificity, positive predictive value and negative predictive value of AVS in diagnosing CAD were 63.8, 71.3, 61.7 and 73.1%, respectively. Early lesions of AVS were characterized by accumulation of lipid and infiltration of macrophages and T lymphocytes as indicated by immunohistochemical staining. Late lesions were characterized by formation of calcific plaques, proliferation of fibrous connective tissue and immunohistochemical staining identifying a few macrophages or T lymphocytes and little lipid accumulation on the surface of aortic valve leaflets. Late lesions in the basement of aortic valve leaflets were characterized by hyperplastic granulation tissues. Three aortic valve leaflets from the non-AVS group were characterized by nonspecific thickened tips, increased collagen, no calcification, no lipid accumulation and no inflammatory cells. Conclusions: There were significant similarities in clinical risk factors, histopathological alterations of AVS and coronary atherosclerosis. AVS detected by TTE had a high association with coronary arteriosclerosis.

Atorvastatin is a lipid-regulating drug that is commonly used in clinical practice and can stabilize plaques. Increasing evidence shows that statins have anti–heart failure (HF) effects, but their specific mechanism is not clear. The purpose of this study was to investigate the cardioprotective effects of atorvastatin on HF in rats and its mechanism. Continuous intraperitoneal injection of 2.5 mg/kg/w doxorubicin for 6 weeks, with a cumulative dose of 15 mg/kg, was used to induce a rat model of HF. Then, the rats were treated with low-dose atorvastatin, high-dose atorvastatin, or saline for 4 weeks. In the DOX-treated groups, echocardiography showed decreases in left ventricular ejection fraction and fractional shortening and increases in left ventricular end-diastolic diameter and left ventricular posterior wall thickness compared with those in the control group, and increased levels of brain natriuretic peptide and Hsp70 were also found in the doxorubicin-treated groups. Compared with saline intervention, atorvastatin ameliorated left ventricular ejection fraction, fractional shortening, left ventricular end-diastolic diameter, and left ventricular posterior wall thickness (a significant difference was observed only in the high-dose group) and reduced serum brain natriuretic peptide. Hematoxylin and eosin staining showed that atorvastatin ameliorated myocardial injury. The improvement in cardiac function induced by atorvastatin was accompanied by increased Hsp70 expression, decreased p-ERK and p-JNK expression, and a reduction in myocardial fibrosis shown by Masson staining. In addition, atorvastatin had a protective effect on the myocardial apoptosis signaling pathway, with increased p-Akt expression and downregulated cleaved caspase-3 expression, and the reduction in myocardial apoptosis was confirmed by a TUNEL assay. Therefore, our experiments demonstrated that atorvastatin may protect cardiac function by modulating Hsp70, p-Akt, p-ERK, and p-JNK signaling to reduce myocardial fibrosis and myocardial apoptosis.