Receptor for Advanced Glycation End Products (RAGE) and Implications for the Pathophysiology of Heart Failure

Ramasamy, Ravichandran; Schmidt, Ann Marie

doi:10.1007/s11897-012-0089-5

Cited by 72 publications

(53 citation statements)

References 70 publications

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“…Although results from NOD1 knockout mice have not been reported for the heart, NOD1 activation induced cardiac dysfunction with increased cardiac fibrosis and cardiomyocyte apoptosis [26], suggesting a detrimental role for this receptor in this context. RAGE knockout has beneficial effects following myocardial ischaemia/reperfusion injury [64,65], in keeping with other studies focused on RAGE activity in cardiac remodelling [66]. It is of course worth noting that knockout mouse studies have their limitations, however they can be very informative for determining the role of proteins particularly where other tools are lacking.…”

Section: Damp Receptors and Cardiac Remodellingsupporting

confidence: 60%

Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs)

Turner

2016

Journal of Molecular and Cellular Cardiology

168

124

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Cardiac fibroblasts (CF) are well-established as key regulators of extracellular matrix (ECM) turnover in the context of myocardial remodelling and fibrosis. Recently, this cell type has also been shown to act as a sensor of myocardial damage by detecting and responding to damage-associated molecular patterns (DAMPs) upregulated with cardiac injury. CF express a range of innate immunity pattern recognition receptors (TLRs, NLRs, IL-1R1, RAGE) that are stimulated by a host of different DAMPs that are evident in the injured or remodelling myocardium. These include intracellular molecules released by necrotic cells (heat shock proteins, high mobility group box 1 protein, S100 proteins), proinflammatory cytokines (interleukin-1), specific ECM molecules up-regulated in response to tissue injury (fibronectin-EDA, tenascin-C) or molecules modified by a pathological environment (advanced glycation end product-modified proteins observed with diabetes). DAMP receptor activation on fibroblasts is coupled to altered cellular function including changes in proliferation, migration, myofibroblast transdifferentiation, ECM turnover and production of fibrotic and inflammatory paracrine factors, which directly impact on the heart's ability to respond to injury. This review gives an overview of the important role played by CF in responding to myocardial DAMPs and how the DAMP/CF axis could be exploited experimentally and therapeutically.3

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Section: Damp Receptors and Cardiac Remodellingsupporting

confidence: 60%

Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs)

Turner

2016

Journal of Molecular and Cellular Cardiology

168

124

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“…In diabetes, obesity and metabolic dysfunction AGEs accumulate in tissues at an accelerated rate and may act as mediators of diabetic complications (96), (97). AGEs accumulate within the cells and in the extracellular milieu and may have profound effects on the structure and composition of the cardiac interstitium through two major mechanisms (98), (99). First, AGE-mediated crosslinking of extracellular matrix proteins (such as collagens and laminin) may increase cardiac stiffness contributing to the development of diastolic dysfunction.…”

Section: The Molecular Signals Regulating Obesity-associated Fibrosismentioning

confidence: 99%

Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities

Cavalera

Wang

Frangogiannis

2014

Translational Research

219

155

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Cardiac fibrosis is strongly associated with obesity and metabolic dysfunction and may contribute to the increased incidence of heart failure, atrial arrhythmias and sudden cardiac death in obese subjects. Our review discusses the evidence linking obesity and myocardial fibrosis in animal models and human patients, focusing on the fundamental pathophysiologic alterations that may trigger fibrogenic signaling, the cellular effectors of fibrosis and the molecular signals that may regulate the fibrotic response. Obesity is associated with a wide range of pathophysiologic alterations (such as pressure and volume overload, metabolic dysregulation, neurohumoral activation and systemic inflammation); their relative role in mediating cardiac fibrosis is poorly defined. Activation of fibroblasts likely plays a major role in obesity-associated fibrosis; however, inflammatory cells, cardiomyocytes and vascular cells may also contribute to fibrogenic signaling. Several molecular processes have been implicated in regulation of the fibrotic response in obesity. Activation of the Renin-Angiotensin-Aldosterone System, induction of Transforming Growth Factor-β, oxidative stress, advanced glycation end-products (AGEs), endothelin-1, Rho-kinase signaling, leptin-mediated actions and upregulation of matricellular proteins (such as thrombospondin-1) may play a role in the development of fibrosis in models of obesity and metabolic dysfunction. Moreover, experimental evidence suggests that obesity and insulin resistance profoundly affect the fibrotic and remodeling response following cardiac injury. Understanding the pathways implicated in obesity-associated fibrosis may lead to development of novel therapies to prevent heart failure and to attenuate post-infarction cardiac remodeling in obese patients.

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“…The etiology of this increased risk for CVD is multifactorial and includes conventional risk factors, such as genetic and lifestyle factors, as well as drug side-effects (DE Hert et al, 2011;Vancampfort et al, 2013). In addition, considerable data indicate that oxidative stress and AGE accumulation are important features of CVD pathogenesis (Prasad et al, 2012;Ramasamy and Schmidt, 2012;Sugamura et al, 2011;Vancampfort et al, 2013;Yamagishi et al, 2012).…”

Section: Age Metabolism and Cardiovascular Risk In Schizophreniamentioning

confidence: 99%

Advanced glycation end products and schizophrenia: A systematic review

Kouidrat

Amad

Arai

et al. 2015

Journal of Psychiatric Research

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Receptor for Advanced Glycation End Products (RAGE) and Implications for the Pathophysiology of Heart Failure

Cited by 72 publications

References 70 publications

Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs)

Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs)

Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities

Advanced glycation end products and schizophrenia: A systematic review

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