Coronary perivascular fibrosis is associated with impairment of coronary blood flow in patients with non-ischemic heart failure

Dai, Zhehao; Aoki, Tatsuo; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

doi:10.1016/j.jjcc.2012.06.009

Cited by 109 publications

(99 citation statements)

References 40 publications

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“…Perivascular fibrosis in the coronary microvasculature can contribute to myocardial ischemia. 90 This observation highlights the potential contribution of fixed structural changes in coronary arterioles beyond impaired endothelial vasodilator function as a contributor to myocardial ischemia in the absence of obstructive disease of the epicardial coronary arteries.…”

Section: Plaque Without Thrombusmentioning

confidence: 84%

Acute Coronary Syndromes

2017

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Well into the 21st century, we still triage acute myocardial infarction based on the presence or absence of ST segment elevation, a century-old technology. Meanwhile, we have learned a great deal regarding the pathophysiology and mechanisms of acute coronary syndromes (ACS) at clinical, pathological, cellular, and molecular levels. Contemporary imaging studies have shed new light into the mechanisms of ACS. This review discusses these advances and their implications for clinical management of the ACS for the future. Plaque rupture has dominated our thinking about ACS pathophysiology for decades. Yet, current evidence suggests that a sole focus on plaque rupture vastly oversimplifies this complex collection of diseases, and obscures other mechanisms that may mandate different management strategies. We propose to segment coronary artery thrombosis due to plaque rupture into cases with or without signs of concomitant inflammation. This distinction may have substantial therapeutic implications as direct anti-inflammatory interventions for atherosclerosis emerge. Coronary artery thrombosis due to plaque erosion may be on the rise in an era of intense lipid lowering. Identification of patients with of ACS due to erosion may permit a less invasive approach to management than the current standard of care. We also now recognize ACS that occur without apparent epicardial coronary artery thrombus or stenosis. Such events may arise from spasm, microvascular disease, or other pathways. Emerging management strategies may likewise apply selectively to this category of ACS. We advocate this more mechanistic approach to the categorization of ACS to provide a framework for future tailoring, triage, and therapy for patients in a more personalized and precise manner.

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Section: Plaque Without Thrombusmentioning

confidence: 84%

Acute Coronary Syndromes

2017

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“…Furthermore, the coronary arteries of stressed ApoE À/À Fbn1 C1039Gþ/À mice showed a marked increase in perivascular fibrosis, in which the renin-angiotensin-aldosterone system is a known key player [25]. Moreover, it has been reported that perivascular fibrosis is correlated with an impaired coronary blood flow [4]. Indeed, the higher degree of stenosis in the coronary arteries of mentally stressed ApoE À/À Fbn1 C1039Gþ/À mice might have blunted blood flow and we confirmed the activation of the reninangiotensin-aldosterone system, as indicated by the increased plasma levels of aldosterone.…”

Section: Discussionmentioning

confidence: 98%

Chronic intermittent mental stress promotes atherosclerotic plaque vulnerability, myocardial infarction and sudden death in mice

et al. 2015

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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.

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“…Whereas interstitial fibrosis stiffens the myocardium and thereby leads to diastolic and systolic dysfunction, reactive fibrosis in the adventitia of the coronary arteries and arterioles (perivascular fibrosis) can cause narrowing of the vessel lumen and has been associated with impaired coronary blood flow (Dai et al 2012). This might decrease the oxygen supply to the myocardium thereby compromising the survival of cardiomyocytes and predisposing them to ischemic cell death.…”

Section: Reactive Fibrosis: Remodeling Of Remote Myocardiummentioning

confidence: 99%

Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration

2016

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Ischemic cell death during a myocardial infarction leads to a multiphase reparative response in which the damaged tissue is replaced with a fibrotic scar produced by fibroblasts and myofibroblasts. This also induces geometrical, biomechanical, and biochemical changes in the uninjured ventricular wall eliciting a reactive remodeling process that includes interstitial and perivascular fibrosis. Although the initial reparative fibrosis is crucial for preventing rupture of the ventricular wall, an exaggerated fibrotic response and reactive fibrosis outside the injured area are detrimental as they lead to progressive impairment of cardiac function and eventually to heart failure. In this review, we summarize current knowledge of the mechanisms of both reparative and reactive cardiac fibrosis in response to myocardial infarction, discuss the potential of inducing cardiac regeneration through direct reprogramming of fibroblasts and myofibroblasts into cardiomyocytes, and review the currently available and potential future therapeutic strategies to inhibit cardiac fibrosis.Graphical abstractReparative response following a myocardial infarction. Hypoxia-induced cardiomyocyte death leads to the activation of myofibroblasts and a reparative fibrotic response in the injured area. Right top In adult mammals, the fibrotic scar formed at the infarcted area is permanent and promotes reactive fibrosis in the uninjured myocardium. Right bottom In teleost fish and newts and in embryonic and neonatal mammals, the initial formation of a fibrotic scar is followed by regeneration of the cardiac muscle tissue. Induction of post-infarction cardiac regeneration in adult mammals is currently the target of intensive research and drug discovery attempts

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Coronary perivascular fibrosis is associated with impairment of coronary blood flow in patients with non-ischemic heart failure

Abstract: These results indicate that coronary perivascular fibrosis is associated with the impairment of coronary blood flow although not associated with interstitial fibrosis or cardiac function, suggesting that it can be a new therapeutic target to improve coronary microcirculation.

Cited by 109 publications

References 40 publications

Acute Coronary Syndromes

Acute Coronary Syndromes

Chronic intermittent mental stress promotes atherosclerotic plaque vulnerability, myocardial infarction and sudden death in mice

Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration

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