Molecular Mechanism of Vascular Disorders and Thrombosis

Dear Colleagues,

Vascular disorders and thrombosis are responsible for about two thirds of diseases. Diabetes mellitus has experienced a worldwide expansion in both developed countries and in development. The major complications are retinopathy and nephropathy, and it is also frequently associated to peripheral vascular disease and coronary syndrome. There is substantial evidence to support the involvement of advanced glycation end-products (AGE) binding to its receptor (RAGE) in the development of diabetic microvascular complications. Activation of RAGE induces oxidative stress, increased permeability, and an inflammatory response in the vessel wall. RAGE is a member of the immunoglobulin superfamily and was originally described as a transmembrane multiligand receptor. In diabetic patients with end-stage renal disease, low circulating sRAGE is a predictor of cardiovascular mortality, suggesting that sRAGE may protect against AGE-mediated vessel damage. RAGE can bind a wide range of endogenous molecules, including AGEs; the high mobility group box-1 (HMGB-1), which is also called amphoterin-c; β-amyloid peptide; and S100 calgranulins. In endothelial cells, three isoforms of RAGE were detected at significant levels: N-truncated (Nt-RAGE), full length (FL-RAGE, usually called RAGE), and endogenous secretory (esRAGE).

Atherosclerosis was considered to be a major contributor for vascular disorders associated to aging. Aging and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. AGE and RAGE participate in various steps of inflammation. Genetic and epigenetic variations of RAGE are implicated in senescence. AGE present in food may accumulate during life and participate in sarcopenia. Mitochondria have a predominant role in cell life and mitochondrial functions can be altered by AGE–RAGE interactions, leading to apoptosis. RAGE contribution to senescence may involve mTOR (mammalian Target of Rapamycin) and ER stress (Endoplasmic Reticulum stress).

Thrombosis may be responsible for myocardial infarction and stroke. Alteration of the vascular wall and endothelium may trigger coagulation and platelet aggregation, leading to vascular occlusion. Atrial fibrillation was found to be at the origin of thrombus formation and migration to the cerebral vessels leading to cerebral vascular occlusion. Prevention by anticoagulants or antiaggregating agents demonstrated the efficiency of such a strategy.

In cancer, neoangiogenesis and vascular dysfunction are important factors for the development of tumors and tumor migration. Neovascularization is essential for growth and spread of primary and metastatic tumors. Endothelial–monocyte activating polypeptide (EMAP) II potently inhibits tumor growth and appears to have antiangiogenic activity. Neovascularization of the mouse cornea was prevented by EMAP II. Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume. Tumors from human breast carcinoma-derived MDA-MB 468 cells were suppressed by >80% in EMAP II-treated animals. In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. Tumor-suppressive mediators such as EMAP II with antiangiogenic properties allow it to target growing endothelium and limit establishment of neovasculature.

Contributions to this Special Issue will provide new insights into the molecular mechanism of vascular disorders and thrombosis.

Pr. Jean-Luc Wautier
Dr. Marie-Paule Wautier
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• vascular dysfunction
• endothelium
• thrombosis
• diabetes
• atherosclerosis
• ageing
• glycation
• cell adhesion
• receptors
• angiogenesis