Stress, inflammation and cardiovascular disease.
Various psychosocial factors have been implicated in the etiology and pathogenesis of certain cardiovascular diseases such as atherosclerosis, now considered to be the result of a chronic inflammatory process. In this article, we review the evidence that repeated episodes of acute psychological stress, or chronic psychologic stress, may induce a chronic inflammatory process culminating in atherosclerosis. These inflammatory events, caused by stress, may account for the approximately 40% of atherosclerotic patients with no other known risk factors. Stress, by activating the sympathetic nervous system, the hypothalamic-pituitary axis, and the renin-angiotensin system, causes the release of various stress hormones such as catecholamines, corticosteroids, glucagon, growth hormone, and renin, and elevated levels of homocysteine, which induce a heightened state of cardiovascular activity, injured endothelium, and induction of adhesion molecules on endothelial cells to which recruited inflammatory cells adhere and translocate to the arterial wall. An acute phase response (APR), similar to that associated with inflammation, is also engendered, which is characterized by macrophage activation, the production of cytokines, other inflammatory mediators, acute phase proteins (APPs), and mast cell activation, all of which promote the inflammatory process. Stress also induces an atherosclerotic lipid profile with oxidation of lipids and, if chronic, a hypercoagulable state that may result in arterial thromboses. Shedding of adhesion molecules and the appearance of cytokines, and APPs in the blood are early indicators of a stress-induced APR, may appear in the blood of asymptomatic people, and be predictors of future cardiovascular disease. The inflammatory response is contained within the stress response, which evolved later and is adaptive in that an animal may be better able to react to an organism introduced during combat. The argument is made that humans reacting to stressors, which are not life-threatening but are "perceived" as such, mount similar stress/inflammatory responses in the arteries, and which, if repetitive or chronic, may culminate in atherosclerosis.
Black
Paul H
PH
epartment of Microbiology, Boston University School of Medicine, Room L-504, 715 Albany Street, Boston, MA 02118, USA. pblack@bu.edu
Garbutt
Lisa D
LD
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005342:Fibrinolysis / Q000502:physiology; D005934:Glucagon / Q000378:metabolism; D006710:Homocysteine / Q000096:biosynthesis; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D012083:Renin / Q000096:biosynthesis; D012307:Risk Factors; D013315:Stress, Psychological / Q000378:metabolism / Q000523:psychology*; D013373:Substance P / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000209:Acute-Phase Proteins; D000305:Adrenal Cortex Hormones; D002395:Catecholamines; D016207:Cytokines; D019010:Vascular Cell Adhesion Molecule-1; D006710:Homocysteine; D019382:Human Growth Hormone; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P; D005934:Glucagon; D012083:Renin