title: Chronic intermittent mental stress promotes atherosclerotic plaque vulnerability, myocardial infarction and sudden death in mice.
abstract: Vulnerable atherosclerotic plaques are prone to plaque rupture leading to acute cardiovascular syndromes and death. Elucidating the risk of plaque rupture is important to define better therapeutic or preventive strategies. In the present study, we investigated the effect of chronic intermittent mental stress on atherosclerotic plaque stability and cardiovascular mortality in apolipoprotein E-deficient (ApoE(-/-)) mice with a heterozygous mutation in the fibrillin-1 gene (Fbn1(C1039G+/)(-)). This mouse model displays exacerbated atherosclerosis with spontaneous plaque ruptures, myocardial infarction and sudden death, when fed a Western-type diet (WD). Female ApoE(-/-)Fbn1(C1039G+/-) mice were fed a WD for up to 25 weeks. After 10 weeks WD, mice were divided in a control (n = 27) and mental stress (n = 29) group. The chronic intermittent mental stress protocol consisted of 3 triggers: water avoidance, damp bedding and restraint stress, in a randomly assigned order lasting 6 h every weekday for 15 weeks. Chronic intermittent mental stress resulted in a significant increase in the amount of macrophages in atherosclerotic plaques of the proximal ascending aorta, whereas type I collagen and fibrous cap thickness were decreased. The coronary arteries of mental stress-treated mice showed larger plaques, more stenosis, and an increased degree of perivascular fibrosis. Moreover, myocardial infarctions occurred more frequently in the mental stress group. As compared to the control group, the survival of stressed ApoE(-/-)Fbn1(C1039G+/-) mice decreased from 67% to 52% at 25 weeks WD, presumably due to myocardial infarctions. In conclusion, chronic intermittent mental stress promotes plaque instability, myocardial infarctions, and mortality of ApoE(-/-)Fbn1(C1039G+/-) mice.
authors.affiliation: Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium. Electronic address: lynn.roth@uantwerpen.be.
authors.forename: Lynn
authors.initials: L
authors.lastname: Roth
authors.affiliation: Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
authors.forename: Miche
authors.initials: M
authors.lastname: Rombouts
authors.affiliation: Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
authors.forename: Dorien M
authors.initials: DM
authors.lastname: Schrijvers
authors.affiliation: Laboratory of Pharmacology, University of Antwerp, Antwerp, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Lemmens
authors.affiliation: Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
authors.forename: Gilles W
authors.initials: GW
authors.lastname: De Keulenaer
authors.affiliation: Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Martinet
authors.affiliation: Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium.
authors.forename: Guido R Y
authors.initials: GR
authors.lastname: De Meyer
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003324:Coronary Artery Disease / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D020022:Genetic Predisposition to Disease; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics; D009203:Myocardial Infarction / Q000209:etiology*; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D012307:Risk Factors; D012422:Rupture, Spontaneous; D013315:Stress, Psychological / Q000150:complications*; D013997:Time Factors; D054392:Adipokines
chemical_list: D001057:Apolipoproteins E; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605724:Fbn1 protein, mouse; D054392:Adipokines
keywords: Atherosclerosis; Coronary stenosis; Mental stress; Myocardial infarction; Perivascular fibrosis; Survival