Endocan in Hypertension and Cardiovascular Disease

Abstract

In their pilot study, Balta et al reported that circulating endocan (endothelial cell specific molecule 1 [ESM-1]) levels may represent a new marker of essential hypertension. They found that in 18 patients with newly diagnosed hypertension, serum endocan levels correlated significantly with carotid intimamedia thickness (cIMT) and high-sensitivity C-reactive protein (hsCRP) compared with 23 normotensive controls. Therefore, Balta et al suggested that circulating endocan levels may represent a new marker for essential hypertension. Endocan is a protein encoded by the ESM-1 gene in humans. Due to possible confusion, it must be clarified that endocan is not related to endocannabinoids that are endogenous mediators that elicit multiple biological effects similar to those of marijuana. The focus of this editorial is specifically on endocan and its CV relationships. Endocan is a recombinant proteoglycan that can be produced from engineered HEK293 cells with efficient longterm production. This availability opens new opportunities to study the structure and functions of endocan. Abid et al tested the hypothesis that endocan, as a novel soluble dermatan sulfate proteoglycan, is differentially expressed in the intact endothelium and that site-specific expression is mediated by signals in the local microenvironment. Using a combination of analytical techniques, they reported that endocan is preferentially expressed in the endothelial lining of tumor xenografts, including human nonsmall cell lung cancer, rat glioma, and human renal cell carcinoma. They found that in vitro expression of endocan in human umbilical vein endothelial cells (HUVECs) was upregulated by a tumor cell-conditioned medium and that this was inhibited by the addition of neutralizing antibody to vascular endothelial growth factor (VEGF). The authors also found that treatment of HUVEC with VEGF resulted in a doseand time-dependent increase in messenger RNA (mRNA) in endocan. It therefore appeared to them that endocan is preferentially expressed in tumor endothelium in vivo with its expression regulated by tumor-derived factors. Akkok et al reported that peripheral blood stem cell (PBSC) collection in patients with multiple myeloma using PBSC apheresis decreased the angioregulatory cytokines, angiopoietin 22 and VEGF, which had been found to be increased in the patients with myeloma, while at the same time, PBSC apheresis resulted in an increase in endocan levels as a microvascular endothelial marker. Rennel et al appeared to show that among angiogenic growth factors, VEGF-A is a specific inducer of endocan transcription. This translates into increased protein levels in VEGF-A-treated endothelial cells. Rennel et al suggested that increased endocan protein expression in human renal cancer supports its role in tumor growth. Similar supportive data are available for colorectal cancer. When colorectal cancer is present, the expression of endocan is downregulated. However, endocan is positively correlated with tissue differentiation in colorectal cancer, which suggests that endocan is associated with the development and differentiation of colorectal cancer. Zhang et al studied endocan as a novel human endothelial cell-specific molecule whose expression is regulated by cytokines and VEGF. They found that endocan was expressed in actively proliferative or neogenic tissues and cells such as the germinal centers of lymph nodes, bronchial epithelium, neovasculature, endothelium, and glandular tissues. Endocan was not present in silent or resting tissues of cells such as the endothelium of the spleen and large arteries. Zhang et al considered that endocan may function as a marker for angiogenesis or oncogenesis and that the gene for endocan might be a candidate gene for the development of inflammatory tissue, metastases, neoplasia, and the development of tumors such that the expression level of endocan may be of value in early diagnosis and prognosis of some tumors. In line with this, Roudnicky et al found that both endocan and VEGF-A levels were more elevated in the plasma of patients with invasive bladder cancer than in healthy individuals. They therefore postulated that endocan might function as a useful biomarker for monitoring disease progression and the efficacy of therapies to target VEGF-A in patients with bladder cancer. Endocan has also been found to be overexpressed in renal clear cell carcinomas and as a result it may be a target marker for follow-up of these cancers and a potential way to evaluate their response to antiangiogenic therapies. Serum endocan has