Mouse model of myocardial remodelling after ischemia: role of intercellular adhesion molecule-1

Metzler, Bernhard; Mair, Johannes; Lercher, Angelika; Schaber, Claudia; Hintringer, Florian; Pachinger, Otmar; Xu, Qingbo

doi:10.1016/s0008-6363(00)00261-3

Cited by 55 publications

(42 citation statements)

References 27 publications

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“…This study has further explored the expression of proinflammatory and profibrogenic mediators as well as cells involved in cardiac repair/remodeling at these sites. Adhesion molecules and chemokines are contributory to inflammatory cell infiltration in the injured tissue and trigger the inflammatory response (14,28). In ANG II-treated animals, we observed enhanced expression of ICAM-1 and MCP-1 at the perivascular space and sites of microscopic injury in both left and right ventricles, which is accompanied with accumulated macrophages.…”

Section: Discussionmentioning

confidence: 78%

ANG II-induced cardiac molecular and cellular events: role of aldosterone

Zhao

Ahokas²,

Weber³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Chronic elevation of circulating ANG II is associated with cardiac remodeling in patients with hypertension and heart failure. The underlying mechanisms, however, are not completely defined. Herein, we studied ANG II-induced molecular and cellular events in the rat heart as well as their links to the redox state. We also addressed the potential contribution of aldosterone (ALDO) on ANG II-induced cardiac remodeling. In ANG II-treated rats, and compared with controls, we found: 1) the expression of proinflammatory/profibrogenic mediators was significantly increased in the perivascular space and at the sites of microscopic injury in both ventricles; 2) macrophages and myofibroblasts were primary repairing cells at these sites, together with increased fibrillar collagen volume; 3) apoptotic macrophages and myofibroblasts were evident at the same sites; 4) NADPH oxidase (gp91 phox ) was significantly enhanced at these regions and primarily expressed by macrophages, whereas superoxide dismutase and catalase levels remained unchanged; 5) plasma 8-isoprostane levels were significantly increased; and 6) blood pressure was significantly elevated. Losartan treatment completely prevented cardiac oxidative stress as well as molecular/cellular responses and normalized blood pressure. Spironolactone treatment partially suppressed the cardiac inflammatory/fibrogenic responses and redox state. Thus chronic elevation of circulating ANG II is accompanied by a proinflammatory/profibrogenic phenotype involving vascular and myocardial remodeling in both ventricles. Enhanced reactive oxygen species production at these sites and increased plasma 8-isoprostane indicate the involvement of oxidative stress in ANG II-induced cardiac injury. ALDO contributes, in part, to ANG II-induced cardiac molecular and cellular responses. cardiac remodeling; angiotensin II; aldosterone; oxidative stress; rats AS A CIRCULATING HORMONE, endocrine properties of ANG II are integral to the regulation of blood pressure and volume homeostasis. However, chronic elevation of circulating ANG II, such as occurs with congestive heart failure and hypertension, is inappropriate and has adverse consequences. For example, such neurohormonal activation has been related to a diverse number of vascular diseases, including atherosclerotic coronary artery disease, cardiac perivascular fibrosis, and diabetes (6,8). An important vascular effect of ANG II is its induction of oxidative stress and a proinflammatory phenotype. Type I ANG II (AT 1 ) receptor blockade can prevent the unfavorable vascular effects by ANG II through hypertension-dependent and -independent mechanisms (1,18,22). Our previous studies have demonstrated that, in addition to vascular remodeling, elevation of circulating ANG II levels also leads to extensive microscopic myocardial repair/remodeling in both left and right ventricles in rats (21, 22). However, ANG II-induced myocardial molecular/cellular events and their relation to oxidative stress have not been fully explored.ANG II stimulates aldosterone ...

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Section: Discussionmentioning

confidence: 78%

ANG II-induced cardiac molecular and cellular events: role of aldosterone

Zhao

Ahokas²,

Weber³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Neutrophil depletion in animals undergoing reperfused myocardial infarction led to a marked decrease in infarct size [210,211] suggesting that a significant amount of myocardial injury induced by coronary artery occlusion followed by reperfusion may be neutrophil-dependent [212]. Although ICAM-1 deficient mice exhibited less myocardial injury at an early stage, they showed no significant difference in infarct size and scar formation after 1-3 weeks of reperfusion [213]. In addition, mice with a combined deficiency in both ICAM-1 and P-selectin showed no difference in infarct size due to myocardial ischemia and reperfusion despite exhibiting impaired neutrophil trafficking [186].…”

Section: The Concept Of Neutrophil-mediated Cardiomyocyte Injurymentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

568

499

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Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

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“…Once again compared to wild type, they showed no difference in infarct size, even after 1-3 wk [59] . The same applies to mice with ICAM1 and P-selectin deficiency.…”

Section: Ischemia/reperfusion Injurymentioning

confidence: 83%

Innate immune receptors in heart failure: Side effect or potential therapeutic target?

Wagner

Felix

Riad

2014

WJC

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Heart failure (HF) is a leading cause of mortality and morbidity in western countries and occasions major expenses for public health systems. Although optimal medical treatment is widely available according to current guidelines, the prognosis of patients with HF is still poor. Despite the etiology of the disease, increased systemic or cardiac activation of the innate immune system is well documented in several types of HF. In some cases there is evidence of an association between innate immune activation and clinical outcome of patients with this disease. However, the few large trials conducted with the use of anti-inflammatory medication in HF have not revealed its benefits. Thus, greater understanding of the relationship between alteration in the immune system and development and progression of HF is urgently necessary: prior to designing therapeutic interventions that target pathological inflammatory processes in preventing harmful cardiac effects of immune modulatory therapy. In this regard, relatively recently discovered receptors of the innate immune system, i.e. , namely toll-like receptors (TLRs) and nodlike receptors (NLRs)-are the focus of intense cardiovascular research. These receptors are main up-stream regulators of cytokine activation. This review will focus on current knowledge of the role of TLRs and NLRs, as well as on downstream cytokine activation, and will discuss potential therapeutic implications.

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Mouse model of myocardial remodelling after ischemia: role of intercellular adhesion molecule-1

Cited by 55 publications

References 27 publications

ANG II-induced cardiac molecular and cellular events: role of aldosterone

ANG II-induced cardiac molecular and cellular events: role of aldosterone

The immune system and cardiac repair

Innate immune receptors in heart failure: Side effect or potential therapeutic target?

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