The Role of Leukocytes in Diabetic Cardiomyopathy

Bajpai, Anamika; Tilley, Douglas G.

doi:10.3389/fphys.2018.01547

Cited by 60 publications

(68 citation statements)

References 177 publications

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“…Secretion of pro‐inflammatory cytokines from obese adipose tissue is thought to result in dysregulation of adipocyte metabolism with increased release of non‐esterified FAs, which over time leads to ectopic fat deposition, including in the form of epicardial fat. The latter contributes to a local pro‐inflammatory environment of adjacent cardiomyocytes with a substantial increase in macrophage infiltration . The development of inflammation in T2DM has been extensively reviewed, and here we focus on the key concepts of how a low‐grade systemic inflammation in T2DM affects mitochondrial metabolism.…”

Section: Pathophysiology Of Disturbances In Mitochondrial Metabolism mentioning

confidence: 99%

“…The latter contributes to a local pro-inflammatory environment of adjacent cardiomyocytes 92 with a substantial increase in macrophage infiltration. 93 The development of inflammation in T2DM has been extensively reviewed, 94 and here we focus on the key concepts of how a low-grade systemic inflammation in T2DM affects mitochondrial metabolism.…”

Section: Systemic Inflammation and Cardiac Mitochondrial Function Imentioning

confidence: 99%

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Altered mitochondrial metabolism in the insulin‐resistant heart

et al. 2019

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Obesity‐induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA‐induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.

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Section: Pathophysiology Of Disturbances In Mitochondrial Metabolism mentioning

confidence: 99%

Section: Systemic Inflammation and Cardiac Mitochondrial Function Imentioning

confidence: 99%

Altered mitochondrial metabolism in the insulin‐resistant heart

et al. 2019

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“…DCM is a major cause of heart failure [4,5]. The progression of diabetes mellitus to diabetic cardiomyopathy involves the interplay of several mechanisms: oxidative damage, inflammation, apoptosis, mitochondrial dysfunction, and overactivation of Raas (Renin-angiotensin aldosterone system), as illustrated in Figure 1 [6,7]. Inflammation is a form of defense and protection from infections and tissue damage; however, the uncontrolled regulation of immune responses can lead to excessive tissue damage [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Diabetes triggers lower levels of systemic inflammation in the cardiomyocytes as an early response to myocardial injury due to the overproduction of mitochondrial ROS. This systemic inflammation triggers the recruitment of leukocytes and causes the secretion of pro-inflammatory cytokines and chemokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) [6,12]. Further exposure to high concentrations of glucose results in increased production of advanced glycation end products (AGEs).…”

Section: Introductionmentioning

confidence: 99%

Effects of Anchomanes difformis on Inflammation, Apoptosis, and Organ Toxicity in STZ-Induced Diabetic Cardiomyopathy

et al. 2020

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Persistent hyperglycemia is known to cause enhanced generation of reactive oxygen species in diabetes. Several inflammatory cytokines are induced by oxidative stress, and their release also leads to increased oxidative stress; this makes oxidative stress one of the important factors in the development of chronic inflammation and other immune responses. These have been implicated in the development of diabetic complications such as nephropathy and cardiomyopathy. Anchomanes difformis has been shown to possess antioxidant and anti-inflammatory potentials. The present study investigated the immunomodulatory potential and the antiapoptotic ability of Anchomanes difformis to ameliorate heart toxicity and injury in type II diabetes. Two weeks of fructose (10%) administration followed by single intraperitoneal injection of streptozotocin (40 mg/kg) were used to induce type II diabetes in male Wistar rats. Leaf extract (aqueous) of Anchomanes difformis (200 and 400 mg/kg) was administered orally for six weeks. Blood glucose concentrations and body weights before and after interventions were determined. Interleukin (IL)-1β, IL-6, IL-10, IL-18, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor alpha (TNFα) were measured in the heart homogenates. Catalase (CAT), superoxide dismutase (SOD), total protein, oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS), and heart-type fatty acid-binding protein (H-FABP) levels were determined. Expressions of transcription factors (Nrf 2 and NFkB/p65) and apoptotic markers were also investigated in the heart. Anchomanes difformis administration reduced pro-inflammatory cytokines, increased anti-inflammatory markers, and enhanced antioxidant defense in the heart of diabetic treated animals. Anchomanes difformis is a new, promising therapeutic agent that can be explored for the treatment of pathological conditions associated with immune responses and will be a useful tool in the management of associated diabetic complications.

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“…Fibrosis and inflammation are essential physiological processes that follow essentially all cardiac pathologies (Swirski and Nahrendorf, 2018). During inflammation, leukocytes function to resolve injury and defend the host through several eloquent mechanisms (Kondo, 2010;Bajpai and Tilley, 2018). The existing literature suggests several connections between leukocyte driven inflammation and cardiac fibrosis.…”

Section: Leukocyte Involvement In Cardiac Fibrosismentioning

confidence: 99%

Leukocyte-Dependent Regulation of Cardiac Fibrosis

Okyere

Tilley

2020

Front. Physiol.

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Cardiac fibrosis begins as an intrinsic response to injury or ageing that functions to preserve the tissue from further damage. Fibrosis results from activated cardiac myofibroblasts, which secrete extracellular matrix (ECM) proteins in an effort to replace damaged tissue; however, excessive ECM deposition leads to pathological fibrotic remodeling. At this extent, fibrosis gravely disturbs myocardial compliance, and ultimately leads to adverse outcomes like heart failure with heightened mortality. As such, understanding the complexity behind fibrotic remodeling has been a focal point of cardiac research in recent years. Resident cardiac fibroblasts and activated myofibroblasts have been proven integral to the fibrotic response; however, several findings point to additional cell types that may contribute to the development of pathological fibrosis. For one, leukocytes expand in number after injury and exhibit high plasticity, thus their distinct role(s) in cardiac fibrosis is an ongoing and controversial field of study. This review summarizes current findings, focusing on both direct and indirect leukocyte-mediated mechanisms of fibrosis, which may provide novel targeted strategies against fibrotic remodeling.

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The Role of Leukocytes in Diabetic Cardiomyopathy

Cited by 60 publications

References 177 publications

Altered mitochondrial metabolism in the insulin‐resistant heart

Altered mitochondrial metabolism in the insulin‐resistant heart

Effects of Anchomanes difformis on Inflammation, Apoptosis, and Organ Toxicity in STZ-Induced Diabetic Cardiomyopathy

Leukocyte-Dependent Regulation of Cardiac Fibrosis

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