Abstract
Loneliness and social isolation are common sources of chronic stress in modern society. Epidemiological studies have demonstrated that loneliness and social isolation increase mortality risk as much as smoking or alcohol consumption and more than physical inactivity or obesity. Loneliness in human is associated with higher blood pressure whereas enhanced atherosclerosis is observed in animal models of social isolation. Loneliness and social isolation lead to activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, enhanced sympathetic nerve activity, impaired parasympathetic function and a proinflammatory immune response. These mechanisms have been implicated in the development of cardiovascular disease conferred by social isolation although a causal relationship has not been established so far. There is evidence that oxidative stress is likely to be a key molecular mechanism linking chronic psychosocial stress to cardiovascular disease. NADPH oxidase-mediated oxidative stress in the hypothalamus has been shown to be required for social isolation-induced HPA axis activation in socially isolated rats. Oxidative stress in the rostral ventrolateral medulla is also a key regulator of sympathetic nerve activity. In the vasculature, oxidative stress increases vascular tone and promote atherogenesis through multiple mechanisms. Thus, preventing oxidative stress may represent a therapeutic strategy to reduce the detrimental effects of social stress on health.