Ghrelin, a newly discovered bioactive peptide, is a natural endogenous ligand of the growth hormone (GH) secretagogue receptor and initially identified as a strong stimulant for the release of GH. Subsequent research has shown that ghrelin and its various receptors are ubiquitous in many other organs and tissues. Moreover, they participate in the regulation of appetite, energy, bodyweight, metabolism of glucose and fat, as well as modulation of gastrointestinal, cardiovascular, pulmonary, immune functions and cell proliferation/apoptosis. Increasing evidence has demonstrated that ghrelin has a close relationship with cardiovascular system. Ghrelin and its receptors are widely distributed in cardiovascular tissues, and there is no doubt that the effects of ghrelin in the cardiovascular system are mediated not only via its growth-hormone-releasing effect but also by its direct effects on the heart. Exogenous administration of ghrelin can dilate peripheral blood vessels, constrict coronary artery, improve endothelial function, as well as inhibit myocardial cell apoptosis. So, ghrelin may have cardiovascular protective effect, including lowering of blood pressure, regulation of atherosclerosis, and protection from ischemia/reperfusion injury as well as improving the prognosis of myocardial infarction and heart failure. Some of these new functions of ghrelin may provide new potential therapeutic opportunities for ghrelin in cardiovascular medicine. In this paper, we will review the existing evidence for cardiovascular effects of ghrelin, including the cardiovascular function, the variations in ghrelin plasma levels in pathophysiologicalogical conditions, the possible protective mechanisms of ghrelin, as well as its future potential therapeutic roles.

Objective-The liver X receptors (LXRs) regulate a set of genes involved in lipid metabolism and reverse cholesterol transport. We investigated the mechanism by which shear stress regulates LXR in vascular endothelial cells (ECs). Methods and Results-Western blot showed that the protein level of LXR␣ and its target ABCA1 in the mouse thoracic aorta was higher than that in the aortic arch. As well, the mRNA level of LXR and its target genes ABCA1, ABCG1, ApoE, and LPL in the thoracic aorta was higher. In vitro, bovine aortic ECs were subjected to a steady laminar flow (12 dyne/cm 2 ). The expressions of LXR and the LXR-mediated transcription were increased by laminar shear stress. Laminar flow increased LXR-ligand binding and the gene expression of sterol 27-hydroxylase (CYP27), which suggests an increased level of LXR ligand in ECs. This effect was attenuated by LXR␣ and CYP27 RNAi. The decrease of LXR in the aorta of PPAR␥ ϩ/Ϫ mice and that of C57 mice fed with PPAR␥ antagonist suggest the involvement of PPAR␥ in the LXR induction by flow. Laminar shear stress in the straight parts of the arterial tree enhances vascular functioning, including the regulation of vascular tone, inhibition of cell proliferation and thrombosis, and augmentation of antiinflammatory effects. In contrast, disturbed flows with large oscillation near bifurcations and curvatures are considered proatherogenic. Thus, laminar shear stress is atheroprotective, whereas disturbed flow patterns are atheroprone. At the molecular and cellular levels, endothelial cells (ECs) have distinct mechanotransduction mechanisms responding to laminar versus disturbed flow patterns, which predispose the vessel wall to other chemical atherogenic factors. [3][4][5][6][7] In vitro flow channel experiments have revealed the atherprotection of steady laminar flow through promoting the expression of antioxidative and antiinflammatory genes, antiapoptosis, and EC cycle arrest. 8 -10 Histochemical and biochemical study has led to the hypothesis that impaired lipid homeostasis in the vessel wall induces the accumulation of low-density lipoprotein (LDL) and its metabolic products in the subendothelial space, macrophages, and vascular smooth muscle cells, thus leading to intimal thickening and plaque formation. 11 However, the mechanism by which local flow patterns cause impaired lipid homeostasis is still unclear. Conclusion-LaminarBelonging to the nuclear receptor superfamily, the liver X receptors (LXRs), including LXR␣ and LXR␤, play central roles in the transcriptional regulation of genes that participate in reverse cholesterol transport and lipid metabolism. Synthetic LXR agonists promote cholesterol efflux and inhibit the development of atherosclerosis in mice. 12-14 Administering a synthetic LXR ligand to ApoE Ϫ/Ϫ and LDLR Ϫ/Ϫ mice decreased lesion size by approximately 50%. 14 The transplantation of bone marrow from LXR␣␤ Ϫ/Ϫ mice to ApoE Ϫ/Ϫ or LDLR Ϫ/Ϫ recipient mice resulted in a marked increase in lesion size. 13 These results strongly support the notion t...

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Background/Aim: Beta2-glycoprotein I (β2-GPI) is a plasma glycoprotein, which has been implicated in a variety of physiological functions. However, the connection between β2-GPI and breast cancer is mostly unknown. Breast cancer is a malignant tumor that severely impairs women's health worldwide. The aim of the study was to investigate the role of β2-GPI in tumor cells of breast cancer patients and its correlation with tumor prognosis. Materials and Methods: A total of 125 female patients diagnosed with breast cancer were enrolled in the study. The expression of β2-GPI in resected breast tissues was determined by immunohistochemistry (IHC) and correlated with clinicopathological variables by the Chisquared test. The prognostic value of β2-GPI for overall survival (OS) and disease-free survival (DFS) was determined by Kaplan-Meier estimates and the significance of differences was evaluated by the log-rank test. Results: β2-GPI staining was predominantly observed in tumor cells of breast cancer patients and significantly correlated with tumor stage and lymph node metastasis of breast cancer. High β2-GPI expression was significantly correlated with better OS and DFS. Moreover, DFS was found to be significantly better in patients with higher β2-GPI expression, especially those in the early tumor stage groups. Conclusion: High β2-GPI expression levels in tumor cells of breast cancer patients were independent factors predicting a better OS and DFS. β2-GPI activation in high-risk patients may be a potential strategy for reducing breast cancer progression.Beta2-glycoprotein I (β2-GPI) is a glycoprotein, which consists of five complement control protein (CCP) modules (1). The first four CCP domains are composed of approximately 60 amino acids and the fifth CCP domain contains 82 amino acids with a positively charged region (2, 3). β2-GPI displays multiple effects in antiphospholipid syndrome, autoimmune disorders, lipoprotein metabolism, vascular thrombosis, coagulation cascade, and oxidative stress (4-11). However, the role of β2-GPI in carcinogenesis remains unclear.Our preliminary results demonstrated that β2-GPI suppresses endothelial cell migration, proliferation, as well as vascular endothelial growth factor (VEGF)-induced angiogenesis via VEGFR2/ERK/Akt/eNOS signaling pathway (12-14). Alterations in cell migration and proliferation are associated with diverse pathologies such as carcinogenesis (15)(16)(17)(18)(19). Furthermore, we have reported that β2-GPI plays an important role in inhibiting melanoma tumor growth and spread (20). However, the potential relationship between β2-GPI and tumorigenesis is not fully understood.