Social isolation: relationship with cardiovascular diseases

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Abstract

Social and demographic changes in the recent decades have led to an increase in the prevalence of social isolation and loneliness in modern society. Social isolation and loneliness are common but underrated factors that determine health, especially cardiovascular health. In addition, the results of various studies have shown that the negative impact of loneliness and social isolation leads to dysfunction of other systems. Social isolation and loneliness are accompanied by the development of oxidative stress in brain structures. This stress activates neurons in the prefrontal cortex and limbic areas, which is accompanied by prolonged increased production of glucocorticoid hormones, eventually leading to resistance to glucocorticoids. At the same time, the sympathetic nervous system is also activated, which, against the backdrop of resistance to glucocorticoids, causes a persistent increase in blood pressure and the development of a pro-inflammatory state. As a result, lonely people experience increased peripheral vascular resistance and increased blood pressure. In addition, the atherosclerotic changes in the arteries develop faster. Although the molecular mechanisms responsible for increased cardiovascular risk in lonely and socially isolated people are not well studied, these changes have been proven to contribute to an increased risk of developing cardiovascular disease. Current measures to fight against loneliness and social isolation have the potential to reduce their negative impact on health. However, given their limited use, their effectiveness for society as a whole is insufficient. In order to better understand the mechanisms of the negative impact of loneliness and social isolation on cardiovascular health, more in-depth research and the development of more effective interventions are needed.

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About the authors

G. I. Lobov

Pavlov Institute of Physiology of the RAS

Author for correspondence.
Email: LobovGI@infran.ru
Russian Federation, 199034, St. Petersburg

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2. Fig. 1. A diagram illustrating the relationship of loneliness and social isolation with cardiovascular diseases. Loneliness and SI lead to an increased autonomic response to stress and hyperactivity of the sympathetic nervous system, which is accompanied by an increase in total peripheral resistance (OPS), the development of arterial hypertension and coronary heart disease (CHD). SI is associated with higher levels of GC at rest due to excessive activation of GGAX, which leads to GC resistance and chronic inflammation. A high concentration of HA enhances the vasoconstrictive effect of catecholamines and reduces the synthesis of NO by endothelial cells. SI activates the renin-angiotensin-aldosterone system, which also increases OPS and leads to endothelial dysfunction. SI also increases the number of circulating natural killer cells (NK), fibrinogen and other inflammatory mediators, which accelerates the development of atherosclerosis. GGAX – hypothalamic-pituitary-adrenocortical system, GK – glucocorticoid hormones, NO – nitric oxide, IL-1β – interleukin -1β, IL-6 – interleukin 6, -TNFa – tumor necrosis factor α, SNC – sympathetic nervous system, OPS – general peripheral resistance, RAAS – renin-angiotensin-the aldosterone system, blood pressure – blood pressure, coronary artery disease – coronary heart disease.

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3. Fig. 2. The bidirectional relationship between GGAX and the immune system. Glucocorticoids have a negative effect on the immune system, inhibiting further synthesis and release of pro-inflammatory cytokines (dotted red line). Glucocorticoids regulate their own production through negative feedback: through corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) of the hypothalamus and ACTH in the anterior pituitary lobe (dotted red line). Pro-inflammatory cytokines (TNF, IL-1 and IL-6) stimulate the release of glucocorticoids, acting at all three levels of GGAX (solid blue lines).

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