Chapters authored
Endothelial Dysfunction in Cardiovascular Diseases
Endothelium is the inner most cell layer of blood vessels. Endothelial cells make special barrier that separate blood from extravascular tissues. Intact endothelium regulates vascular tone and permeability and maintains non-inflammatory, anti-thrombotic surface. Through its ability to express pro-coagulants, anticoagulants, vasoconstrictors, vasodilators, cell adhesion molecules, and cytokines, the endothelium has emerged as one of the pivotal regulators of vascular homeostasis. Under physiological conditions, endothelial cell sustains a vasodilatory, anticoagulant, and fibrinolytic state in which coagulation, platelet adhesion, as well as leukocyte activation and inflammation are suppressed. In contrast, during endothelial disturbances, a prothrombotic and pro-inflammatory state of vasoconstriction gets support from the endothelial surface. Release of platelet-activating factor (PAF) and endothelin-1 promotes vasoconstriction, whereas production of von Willebrand factor (vWF), tissue factor (TF), and plasminogen activator inhibitor (PAI)-1 shifts the haemostatic balance towards a procoagulant state. Several factors like infection, hyperglycaemia, hyperlipidaemia, malignancy, oxidative stress, and aging can interfere in endothelial function. It is believed that most of the cardiovascular diseases originate from endothelial dysfunction. Endothelial dysfunction has been shown to be involved in atherosclerosis, thrombosis, hypertension, diabetes, and other cardiovascular diseases. In this review we will specifically highlight the role of endothelial dysfunction in development of cardiovascular diseases.
Part of the book: Basic and Clinical Understanding of Microcirculation
Stress-Induced Insulin Resistance: Role of Von Willebrand Factor
Sterile inflammation (SI) is a non-pathogen-induced inflammation where damage-associated molecular patterns (DAMPs) molecules are released from dying cells, which activate Toll-like receptors (TLRs), leading to insulin resistance (IR) and CVDs. The relationship between inflammation and IR is known. However, the role of SI molecules, that is, HMGB1 and circulating nucleic acids (CNAs), [i.e., eRNA and eDNA], in the development of IR is not known. Glucose intolerance is a fundamental clinical characteristic of metabolic syndrome, which is increasingly prevalent and causing illness globally. Hypoxia resulting from various respiratory disorders often coincides with heightened sympathetic activity, poor nitric oxide (NO) production, and insulin resistance (IR). However, the molecular mechanism remains obscure. Therefore, we hypothesized that SI molecules released during stress might impair NO production and IR. We have shown that stress induces the SI molecule (HMGB1), inhibits insulin-induced NO production, and exerts IR through von Willebrand factor (vWF). The putative vWF sequence could be used as a therapeutic drug for the treatment of IR in the future. These data may have important implications for glucose metabolism in patients with disorders characterized by stress-induced IR.
Part of the book: Glucose and Insulin Homeostasis