Potential role of epicardial adipose tissue in coronary artery endothelial cell dysfunction in type 2 diabetes

Ballasy, Noura; Jadli, Anshul; Edalat, Pariya; Kang, Sang–Wook; Hassanabad, Ali Fatehi; Gomes, Karina Pereira; Fedak, Paul W.M.; Patel, Vaibhav

doi:10.1096/fj.202100684rr

Cited by 16 publications

(10 citation statements)

References 69 publications

(148 reference statements)

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“…It is metabolically active, secreting pro- and anti-inflammatory mediators and cytokines. [ 1 2 3 ] With increasing amount of EAT, the balance between pro- and anti-inflammatory markers shifts toward a more pro-inflammatory state. [4] As such, EAT is suggested to locally influence atherosclerosis development.…”

Section: Introductionmentioning

confidence: 99%

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Epicardial adipose tissue is a robust measure of increased risk of myocardial infarction – a meta-analysis on over 6600 patients and rationale for the EPIC-ACS study

Hendricks¹,

Dykun²,

Balcer³

et al. 2021

Medicine

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Background: Epicardial adipose tissue (EAT) surrounds the heart and the coronary vessels. EAT produces pro- and anti-inflammatory cytokines. Several studies have already documented the association of EAT and cardiovascular risk factors as well as coronary artery disease manifestations. Currently computed tomography (CT) is considered the gold standard for measurement of 3-dimensional volume of EAT. In addition, echocardiography might be an easy accessible alternative in particular in an emergency setting. Methods: We performed a metaanalysis of existing studies describing the differences of EAT in patients with and without myocardial infarction. We used established databases and were searching for “epicardial adipose tissue” or “pericardial adipose tissue” and “myocardial infarction”, “coronary events”, or “acute coronary syndrome”. We included over 6600 patients from 7 studies. Random effect models were calculated and all analyses were performed by using the Review Manager 5.3. Results: Patients with myocardial infarction had 37% (confidence interval [0.21-0.54], P value <.001)] higher measures of EAT compared to patients without myocardial infarction. Comparing studies using echocardiography vs CT for assessment of EAT thickness, similar relative differences in EAT with wide overlap of confidence intervals were observed (for echocardiography: 0.4 [0.04-0.76], for CT: 0.36 [0.16-0.57], P value <.001 for both). Conclusions: Patients with myocardial infarction have more EAT as compared to patients without myocardial infarction independently of the used imaging modality. Further prospective studies are needed to evaluate, how quantification of EAT in clinical routine can improve patients management.

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Section: Introductionmentioning

confidence: 99%

“…Epicardial adipose tissue (EAT) surrounds the heart and the coronary vessels. It is metabolically active, secreting pro- and anti-inflammatory mediators and cytokines [1–3] . With increasing amount of EAT, the balance between pro- and anti-inflammatory markers shifts toward a more pro-inflammatory state [4] .…”

Section: Introductionmentioning

confidence: 99%

Epicardial adipose tissue is a robust measure of increased risk of myocardial infarction – a meta-analysis on over 6600 patients and rationale for the EPIC-ACS study

Hendricks¹,

Dykun²,

Balcer³

et al. 2021

Medicine

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“…The gene expression profile for contractile and synthetic genes was performed as described previously [ 27 , 29 ]. Following TaqMan probes for quantitative PCR were used to measure the expression of specified genes: Acta2 (Mm.PT.58.16320644), Myh11 (Mm.PT.58.9236105), Il-6 (Mm.PT.58.10005566), Mmp2 (Mm00439498_m1), Mmp9 (Mm00442991_m1), Col1a1 (Mm00801666_g1), Col3a1 (Mm00802331_m1), and 18S rRNA (Hs.PT.39a.22214856.g).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm

Jadli,

Gomes,

Ballasy

et al. 2023

Bioscience Reports

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Abdominal aortic aneurysm (AAA) represents a debilitating vascular disease characterized by aortic dilatation and wall rupture if it remains untreated. We aimed to determine the effects of Ang 1-7 in a murine model of AAA and to investigate the molecular mechanisms involved. 8-10 weeks old apolipoprotein E-deficient mice (ApoEKO) were infused with Ang II (1.44 mg/kg/day, s.c.) and treated with Ang 1-7 (0.576 mg/kg/day, i.p.). Echocardiographic and histological analyses showed abdominal aortic dilatation and extracellular matrix remodeling in Ang II-infused mice. Treatment with Ang 1-7 led to suppression of Ang II-induced aortic dilatation in the abdominal aorta. The immunofluorescence imaging exhibited reduced smooth muscle cell (SMC) density in the abdominal aorta. The abdominal aortic SMCs from ApoEKO mice exhibited markedly increased apoptosis in response to Ang II. Ang 1-7 attenuated cell death, as evident by increased SMC density in the aorta and reduced annexin V/propidium iodide-positive cells in flow cytometric analysis. Gene expression analysis for contractile and synthetic phenotypes of abdominal SMCs showed preservation of contractile phenotype by Ang 1-7 treatment. Molecular analyses identified increased mitochondrial fission, elevated cellular and mitochondrial reactive oxygen species (ROS) levels, and apoptosis-associated proteins, including Cytochrome C, in Ang II-treated aortic SMCs. Ang 1-7 mitigated Ang II-induced mitochondrial fission, ROS generation, and levels of pro-apoptotic proteins, resulting in decreased cell death of aortic SMCs. These results highlight a critical vasculo-protective role of Ang 1-7 in a degenerative aortic disease; increased Ang 1-7 activity may provide a promising therapeutic strategy against the progression of AAA.

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“… 62 , 63 In an ex vivo model of T2DM, human epicardial adipose tissue treated with diabetic conditions increased the expression of pro-inflammatory cytokines, such as TNF-α and interleukin (IL)-1β, which subsequently induced human coronary artery endothelial cells to acquire an inflammatory phenotype and reduced angiogenic potential. 64 …”

Section: Current Understanding Of the Mechanisms Underlying Diabetic ...mentioning

confidence: 99%

Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy

Phang

Ritchie

Hausenloy

et al. 2022

Cardiovascular Research

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Patients with Type 2 diabetes mellitus (T2DM) frequently exhibit a distinctive cardiac phenotype known as diabetic cardiomyopathy. Cardiac complications associated with T2DM include cardiac inflammation, hypertrophy, fibrosis and diastolic dysfunction in the early stages of the disease, which can progress to systolic dysfunction and heart failure. Effective therapeutic options for diabetic cardiomyopathy are limited and often have conflicting results. The lack of effective treatments for diabetic cardiomyopathy is due in part, to our poor understanding of the disease development and progression, as well as a lack of robust and valid preclinical human models that can accurately recapitulate the pathophysiology of the human heart. In addition to cardiomyocytes, the heart contains a heterogeneous population of non-myocytes including fibroblasts, vascular cells, autonomic neurons and immune cells. These cardiac non-myocytes play important roles in cardiac homeostasis and disease, yet the effect of hyperglycaemia and hyperlipidaemia on these cell types are often overlooked in preclinical models of diabetic cardiomyopathy. The advent of human induced pluripotent stem cells provides a new paradigm in which to model diabetic cardiomyopathy as they can be differentiated into all cell types in the human heart. This review will discuss the roles of cardiac non-myocytes and their dynamic intercellular interactions in the pathogenesis of diabetic cardiomyopathy. We will also discuss the use of sodium-glucose cotransporter 2 inhibitors as a therapy for diabetic cardiomyopathy and their known impacts on non-myocytes. These developments will no doubt facilitate the discovery of novel treatment targets for preventing the onset and progression of diabetic cardiomyopathy.

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Potential role of epicardial adipose tissue in coronary artery endothelial cell dysfunction in type 2 diabetes

Cited by 16 publications

References 69 publications

Epicardial adipose tissue is a robust measure of increased risk of myocardial infarction – a meta-analysis on over 6600 patients and rationale for the EPIC-ACS study

Epicardial adipose tissue is a robust measure of increased risk of myocardial infarction – a meta-analysis on over 6600 patients and rationale for the EPIC-ACS study

Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm

Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy

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