Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research
  Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login  
  Home Print this page Email this page Small font sizeDefault font sizeIncrease font size Users Online: 263       

   Table of Contents      
ORIGINAL ARTICLE
Year : 2020  |  Volume : 151  |  Issue : 6  |  Page : 554-561

Pathogenic gene expression of epicardial adipose tissue in patients with coronary artery disease


1 Department of Physiology, NKP Salve Institute of Medical Sciences & Research Center, Nagpur, Maharashtra, India
2 Department of Medicine, Dew Medicare & Trinity Hospital, Nagpur, Maharashtra, India
3 Environmental Health Division, CSIR-National Environmental Engineering Research Institute, Nagpur, Maharashtra, India
4 Department of Cardiothoracic Surgery, Dr. K.G. Deshpande Memorial Centre, Nagpur, Maharashtra, India

Date of Submission23-Jul-2018
Date of Web Publication21-Jul-2020

Correspondence Address:
Dr Anagha Vinay Sahasrabuddhe
Department of Physiology, NKP Salve Institute of Medical Sciences & Research Centre, Nagpur 440 019, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmr.IJMR_1374_18

Rights and Permissions
   Abstract 


Background & objectives: Coronary artery disease (CAD), a leading cause of mortality and morbidity worldwide has multifactorial origin. Epicardial adipose tissue (EAT) has complex mechanical and thermogenic functions and paracrine actions via various cytokines released by it, which can have both pro- and anti-inflammatory actions on myocardium and adjacent coronaries. The alteration of EAT gene expression in CAD is speculated, but poorly understood. This study was undertaken to find out the difference in gene expression of epicardial fat in CAD and non-CAD patients.
Methods: Twenty seven patients undergoing coronary artery bypass graft (CABG) and 16 controls (non-CAD patients undergoing valvular heart surgeries) were included in the study and their EAT samples were obtained. Gene expressions of uncoupling protein-1, monocyte chemoattractant protein-1 (MCP-1), adiponectin, adenosine A1 receptor (ADORA-1), vascular cell adhesion molecule-1 (VCAM-1) and tumour necrosis factor-alpha (TNF-α) were studied by real-time reverse transcription-polymerase chain reaction. Glucose, insulin, lipid profile, high-sensitivity C-reactive protein, homocysteine, vitamin D, TNF-α and leptin levels were estimated in fasting blood samples and analyzed.
Results: Leptin levels were significantly higher in CABG group as compared to controls (P <0.05), whereas other metabolic parameters were not significantly different between the two groups. MCP-1, VCAM-1 and TNF-α were upregulated in the CABG group as compared to controls. Further, multivariate analysis showed significantly reduced adjusted odds ratio for MCP-1 [0.27; 95% confidence interval: 0.08-0.91] in the CABG group as compared to controls (P <0.05).
Interpretation & conclusions: Our findings showed an alteration in EAT gene expression in CAD patients with significant upregulation of
MCP-1. Further studies with a large sample need to be done to confirm these findings.

Keywords: Adiponectin - CAD - EAT - inflammatory biomarkers - MCP-1 - paracrine


How to cite this article:
Sahasrabuddhe AV, Pitale SU, Sivanesan SD, Deshpande PK, Deshpande SP, Daiwile A. Pathogenic gene expression of epicardial adipose tissue in patients with coronary artery disease. Indian J Med Res 2020;151:554-61

How to cite this URL:
Sahasrabuddhe AV, Pitale SU, Sivanesan SD, Deshpande PK, Deshpande SP, Daiwile A. Pathogenic gene expression of epicardial adipose tissue in patients with coronary artery disease. Indian J Med Res [serial online] 2020 [cited 2020 Sep 29];151:554-61. Available from: http://www.ijmr.org.in/text.asp?2020/151/6/554/290289



Epicardial adipose tissue (EAT) is a visceral fat depot located around heart with no fascia separating it from underlying myocardium [1]. EAT is vascularized by the branches of the coronary arteries. The complex physiological functioning of human epicardial fat is not completely elucidated, but is distinguished by mechanical, metabolic and endocrine/paracrine and thermogenic functions [2].

Mechanically, it protects coronaries against distortion and releases free fatty acids, which are utilized by myocardium as an energy source. It acts as a sink for fatty acids in circulation, protecting heart from lipotoxicity. The expression of uncoupling protein-1 (UCP-1) and related proteins is high in EAT, indicating its role in thermogenesis in humans [1],[2],[3],[4]. It is a source of multiple bioactive cytokines such as leptin, adiponectin, resistin, plasminogen activator inhibitor-1, apelin, tumour necrosis factor-alpha (TNF-α), interleukin-6 and monocyte chemoattractant protein-1 (MCP-1), which are involved in the regulation of endothelial function, coagulation and inflammation through paracrine and endocrine actions [5]. Growing evidence points to the role of epicardial fat involvement in the development of coronary artery disease (CAD)[6]. Owing to its anatomical and functional contiguity with myocardium and coronaries, epicardial fat can secrete a large number of pro-inflammatory and suppressed anti-inflammatory cytokines under pathological conditions [7]. The relative expression (RE) of pro- and anti-inflammatory genes by EAT may be a determinant in the development of CAD [8].

CAD risk in Indians is reported to be significantly higher in the general population than in Caucasians [9]. Asian Indians have more total, subcutaneous and visceral fat for similar body mass index (BMI) and age, compared with Caucasians [10]. The amount of visceral fat in Indians is more for each BMI level when compared with Caucasians and they fit into a term described as 'metabolically obese' normal-weight individuals [11].

Plasma inflammatory biomarkers may not adequately reflect this local tissue inflammation [12]. It is postulated that in the adipose tissue, hypoxia leads to increased expression of inflammatory genes and decreased expression of adiponectin [13]. Treatment with beta-blockers, aspirin, angiotensin converting enzyme (ACE) inhibitors and Ca 2+ channel blockers does not affect the adipocytokine gene expression in the EAT [13]. This study was thus undertaken with the aim to find out pathological functioning of epicardial fat in patients with CAD and the difference in gene expression of EAT in CAD and non-CAD patients.


   Material & Methods Top


Twenty seven consecutive patients meeting inclusion-exclusion criteria undergoing elective coronary artery bypass graft (CABG), at Dr. K.G. Deshpande Memorial Centre, Nagpur, Maharashtra, India, and willing to participate were recruited in the study during February 2016 to October 2017). Written informed consent was obtained from all participants (both cases and controls) before carrying out any study-related procedure. Patients with renal and hepatic insufficiency and those with psychiatric disorders and pregnancy were excluded. Proper history was taken and thorough physical examination was done. The data of echocardiography and angiography were recorded for each patient. Complete drug history and family history were also noted. Their fasting mixed venous blood sample (10 ml) was collected. The investigations performed were fasting glucose (FBS), fasting insulin (in non-diabetic patients), lipid profile, leptin, TNF-α, haemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hsCRP), homocysteine and vitamin D levels. To compare the epicardial fat expression of CAD patients with those without CAD, EAT and fasting blood samples (10 ml) were collected from non-CAD patients (confirmed by angiography) undergoing valvular surgeries (n=16). The study protocol was approved by the Institutional Ethics Committee.

RNA extraction and gene expression:The human epicardial fat tissue (0.5-1 g) biopsy was obtained during CABG. The sample was immediately frozen at −70°C till RNA was extracted. Total RNA was isolated using RNeasy Lipid Tissue Mini Kit (Qiagen, Germany) as per the manufacturer's instructions; 1 μg of total RNA was first converted to cDNA (complementary DNA) using High-Capacity Reverse Transcription kit (Applied Biosystems, USA). Resulting cDNA samples were analyzed for the expression of pro-inflammatory and anti-inflammatory chemokine genes by real-time reverse transcription-polymerase chain reaction (qRT-PCR). Relative quantification of these genes was performed on Applied Biosystems 7300 real-time PCR using EXPRESS SYBR GreenER qPCR SuperMix.

The threshold cycle (Ct) values were obtained for target as well as reference genes from both CABG and control samples. Hypoxanthine phosphoribosyltransferase (HPRT) was used as a reference gene. The target gene set was as follows: adiponectin, UCP-1, MCP-1, vascular cell adhesion molecule-1 (VCAM-1), adenosine receptor A1 (ADORA-1) and TNF-α {Table 1]. The Ct values for each gene type in each group were used to determine the relative expression of that gene. The primers were synthesized by Sigma-Aldrich, USA.
Table 1: Forward and reverse primer sequences for selected genes

Click here to view


The result was expressed as Δ Cti.e., fold change in the expression of the target gene relative to reference gene. The Δ Ct values from control and patients' samples were then compared to obtain the ΔΔ Ct value, which is a reliable indicator of the difference in gene expression between control and experimental samples.

Statistical analysis:Data on parameters such as age, gender, BMI, behavioural habits and biochemical parameters were obtained for patients undergoing CABG as well as other valvular surgeries, referred to as control group in this study. Descriptive statistics such as mean, standard deviation, frequencies and percentages were obtained. Variables measured on numeric scale were compared between the two groups using t test for independent samples, whereas categorical variables were compared using Pearson's Chi-square test.

The Ct values were obtained for target and reference genes for each patient from CABG and control groups and expressed in terms of mean and standard deviation. The expression of target gene was normalized to reference gene expression level to obtained Δ Ct values:Δ Ct= Ct(target gene) − Ct(reference gene).

Further,ΔΔCt value was obtained for each target gene as ΔΔ Ct=Δ Ct(CABG sample) −Δ Ct(control sample). Finally, the fold change, also known as relative expression in qRT-PCR, of target gene expression in CABG sample in comparison with control sample, after normalizing with reference gene was obtained as 2−DDCt, considering a uniform PCR amplification efficiency of 100 per cent across all samples. The significance of difference in the mean normalized expression levels of target genes between the two groups was determined using t test of independent samples and the P values were adjusted for multiple testing correction using Benjamin and Hochberg (BH) method [21]. The multivariate logistic regression analysis was performed with groups as dependent variable and demographic and biochemical parameters as independent variables. Hosmer-Lemeshow test [22] was used to decide the goodness of fit of the model. All the analyses were performed in R-3.2.1 programming tool (R Core Team, Vienna, Austria).


   Results Top


The data on demographic and personal characteristics, metabolic parameters and marker expression were obtained on 27 CABG patients and 16 controls. [Table 2] provides the descriptive statistics for parameters and their comparison between the groups. The mean age of patients in CABG group was significantly higher than that of control group (P <0.01). Gender bias, mean BMI and smoking habit pattern were not significantly different between the two groups. All the patients from CABG group were hypertensive unlike control group, showing significant difference (P <0.001). Dyslipidaemia was also predominantly observed in CABG patients as compared to controls (P <0.001). Mean arterial pressure (MAP) was significantly higher in CABG group than control group (P <0.001). Other biochemical and haematological parameters differed insignificantly between the two groups. Among markers of interest, the mean leptin level was significantly higher in the CABG group as compared to the control group (P <0.05).
Table 2: Descriptive statistics of patient characteristics in the two groups

Click here to view


The relative expression or fold change of six target genes was obtained based on Ct values as given in [Table 3]. It was evident that RE for MCP-1 was 2.7132 indicating upregulation of this gene in CABG patients as compared to controls. This was followed by upregulation of VCAM-1, TNF-a and UCP-1. Adiponectin showed downregulation in CABG patients. The [Figure 1] shows the mean Δ Ct values for these genes in CABG group through column chart. The difference between the means of CABG and control groups for MCP-1 was significant (P <0.05) after BH correction. The Figure also shows the relative expression for different genes. MCP-1 and VCAM-1 were focused in the downstream functional analysis, although the difference for later was not significant.
Table 3: Descriptive statistics for gene expression and relative expression of target genes

Click here to view
Figure 1: Showing mean (±SD) of ΔCtvalues for target genes in coronary artery bypass graft group (n=27) and the relative expression. TNF-α, tumour necrosis factor-alpha; UCP-1, uncoupling protein-1; MCP-1, monocyte chemoattractant protein-1; VCAM-1, vascular cell adhesion molecule-1; ADORA-1, adenosine A1 receptor; ADIN; adiponectin.

Click here to view


Further, the risk of CAD associated with metabolic parameters of interest after adjusting for covariates was obtained [Table 4]. The odds ratio associated with homocysteine, creatinine kinase muscle/brain (CKMB) and TNF-α was close to 1.0, indicating marginal effect of unit increase in these parameters on CAD. Increase in the leptin levels increased the risk of CAD, although not significant. The unit increase in Ct values for MCP-1 decreased the odds of CAD significantly (P <0.05). In other words, decrease in Ct values of MCP-1 (upregulation of MCP-1) increased the risk of CAD.
Table 4: Risk of coronary artery disease associated with different factors

Click here to view



   Discussion Top


The key findings of the study were upregulation and higher expression of pro-inflammatory chemokines MCP-1, TNF-α and VCAM-1 in EAT of patients with CAD as compared to controls. The expression of anti-inflammatory chemokines, adiponectin, ADORA-1 and UCP-1 which are cardioprotective, was downregulated in CAD patients as compared to controls. However, upregulation of MCP-1 expression was observed after adjusting for all confounders. The plasma levels of inflammatory biomarkers such as hsCRP, homocysteine, insufficient vitamin D levels and TNF-α were comparable in both groups. This indicates that EAT may have a larger role to play in the development of CAD. Earlier we have reported that epicardial fat mass correlates positively with diastolic dysfunction [1]. Higher levels of MCP-1, TNF-α and some other chemokines have been reported in different studies [7],[13],[23]. Lower levels of adiponectin in the EAT in CABG patients as compared with non-CAD patients have also been shown [24],[25].

MCP-1 initiates macrophage infiltration of adipose tissue, a hallmark of many studies which have reported presence of inflammatory state of EAT in CAD patients [7],[13],[22],[26],[27],[28]. Hirata et al[26] have reported the presence of greater number of M1 macrophages (inflammatory) as compared to M2 (inactive) in epicardial fat in CAD patients. The fact that atherosclerotic lesions develop in those parts of coronary arteries, which are surrounded completely by epicardial fat and the amount of fat and macrophage infiltration correlate with atherosclerotic plaque size and composition, further emphasizes the inflammatory role of EAT [29]. Expression of MCP-1 by EAT is high as compared with subcutaneous adipose tissue (SAT) and omental fat [26],[30]. The parts of coronaries, which are free of atherosclerotic lesions are also free of adipose tissue [31].

The secretion of inflammatory chemokines such as TNF-α and MCP-1 induces inflammatory cell influx into arterial wall, coronary vasospasm affecting arterial homeostasis, inducing plaque instability and apoptosis [13],[32]. Whole genome analysis of EAT from 29 CAD and 15 non-CAD (undergoing valvular surgeries) patients through microarrays has shown complex overactivation of inflammatory cascades in EAT of CAD patients, whereas negative modulators of inflammation were found to be downregulated in them at transcriptional level [33]. Various pro-inflammatory adipokines released from the EAT increase the expression of VCAM-1, which mediates vascular endothelial inflammation via oxidative stress-dependent NFκB activation [34]. In our study, we found upregulation of VCAM-1 gene from EAT in CAD patients but significant upregulation was seen with MCP-1.

The finding that inflammatory markers are overexpressed in EAT after adjusting for all confounders including hypertension, diabetes, dyslipidaemia, age, gender and BMI signifies the independent role played by EAT in the development of CAD. The expression of adipokines correlates well with the EAT thickness. EAT can be a potential therapeutic target. Drugs such as sodium glucose transporter 2 (SGLT-2) inhibitors reduce EAT thickness. Epicardial fat decreases after very low calorie diet, aerobic exercise and even after bariatric surgery-induced weight loss [35],[36],[37].

Our study had certain limitations. The sample size for the study was modest. This was a single-centre study and there were constraints in getting age- and sex-matched controls as the mean age of valvular heart disease without CAD was low.

In conclusion, the upregulation of expression of inflammatory markers such as MCP-1, TNF-α and VCAM-1 with downregulation of protective molecules such as adiponectin and ADORA-1 remained independent after adjusting for various confounders, indicating a pathological functioning of EAT in the development of CAD. MCP-1 expression was significantly higher in CAD patients as compared with non-CAD patients.

Acknowledgment: Authors acknowledge the contribution of Dr Dhananjay Raje, MDS Bio-Analytics, Nagpur, for data management and statistical analysis.

Financial support & sponsorship: Funding for gene expression study was provided by the Council of Scientific & Industrial Research (CSIR) to CSIR-National Environmental Engineering Research Institute, Nagpur.

Conflicts of Interest: None.



 
   References Top

1.
Sahasrabuddhe AV, Pitale SU, Dhoble SJ, Shivalkar J, Sagdeo MM. Cardiac diastolic dysfunction and regional body fat distribution in insulin resistant peripubertal obese males. J Assoc Physicians India 2016; 64 : 20-6.  Back to cited text no. 1
    
2.
Wu Y, Zhang A, Hamilton DJ, Deng T. Epicardial fat in the maintenance of cardiovascular health. Methodist Debakey Cardiovasc J 2017; 13 : 20-4.  Back to cited text no. 2
    
3.
Iacobellis G, Pond CM, Sharma AM. Different “weight” of cardiac and general adiposity in predicting left ventricle morphology. Obesity (Silver Spring) 2006; 14 : 1679-84.  Back to cited text no. 3
    
4.
Sacks HS, Fain JN, Holman B, Cheema P, Chary A, Parks F, et al. Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: Epicardial fat functioning as brown fat. J Clin Endocrinol Metab 2009; 94 : 3611-5.  Back to cited text no. 4
    
5.
Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: Anatomic, biomolecular and clinical relationships with the heart. Nat Clin Pract Cardiovasc Med 2005; 2 : 536-43.  Back to cited text no. 5
    
6.
Yagi S, Hirata Y, Ise T, Kusunose K, Yamada H, Fukuda D, et al. Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus. Diabetol Metab Syndr 2017; 9 : 78.  Back to cited text no. 6
    
7.
Baker AR, Silva NF, Quinn DW, Harte AL, Pagano D, Bonser RS, et al. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc Diabetol 2006; 5 : 1.  Back to cited text no. 7
    
8.
Sacks HS, Fain JN, Cheema P, Bahouth SW, Garrett E, Wolf RY, et al. Inflammatory genes in epicardial fat contiguous with coronary atherosclerosis in the metabolic syndrome and type 2 diabetes: Changes associated with pioglitazone. Diabetes Care 2011; 34 : 730-3.  Back to cited text no. 8
    
9.
Sekhri T, Kanwar RS, Wilfred R, Chugh P, Chhillar M, Aggarwal R, et al. Prevalence of risk factors for coronary artery disease in an urban Indian population. BMJ Open 2014; 4 : E005346.  Back to cited text no. 9
    
10.
Raji A, Seely EW, Arky RA, Simonson DC. Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J Clin Endocrinol Metab 2001; 86 : 5366-71.  Back to cited text no. 10
    
11.
Ruderman NB, Schneider SH, Berchtold P. The “metabolically-obese,” normal-weight individual. Am J Clin Nutr 1981; 34 : 1617-21.  Back to cited text no. 11
    
12.
Iacobellis G, Bianco AC. Epicardial adipose tissue: Emerging physiological, pathophysiological and clinical features. Trends Endocrinol Metab 2011; 22 : 450-7.  Back to cited text no. 12
    
13.
Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation 2003; 108 : 2460-6.  Back to cited text no. 13
    
14.
Chen H, Chen H, Wu Y, Liu B, Li Z, Wang Z. Adiponectin exerts antiproliferative effect on human placenta via modulation of the JNK/c-Jun pathway. Int J Clin Exp Pathol 2014; 7 : 2894-904.  Back to cited text no. 14
    
15.
Lee JY, Takahashi N, Yasubuchi M, Kim YI, Hashizaki H, Kim MJ, et al. Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes. Am J Physiol Cell Physiol 2012; 302 : C463-72.   Back to cited text no. 15
    
16.
Kim MS, Day CJ, Morrison NA. MCP-1 is induced by receptor activator of nuclear factor-κB ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation. J Biol Chem 2005; 280 : 16163-9.   Back to cited text no. 16
    
17.
Piga R, Naito Y, Kokura S, Handa O, Yoshikawa T. Short-term high glucose exposure induces monocyte-endothelial cells adhesion and transmigration by increasing VCAM-1 and MCP-1 expression in human aortic endothelial cells. Atherosclerosis 2007; 193 : 328-34.  Back to cited text no. 17
    
18.
Nakamura Y, Kano R, Hasegawa A, Watanabe S. Interleukin-8 and tumor necrosis factor alpha production in human epidermal keratinocytes induced by Trichophyton mentagrophytes. Clin Diagn Lab Immunol 2002; 9 : 935-7.   Back to cited text no. 18
    
19.
Evans BA, Elford C, Pexa A, Francis K, Hughes AC, Deussen A, et al. Human osteoblast precursors produce extracellular adenosine, which modulates their secretion of IL-6 and osteoprotegerin. J Bone Miner Res 2006; 21 : 228-36.  Back to cited text no. 19
    
20.
Daiwile AP, Sivanesan S, Izzotti A, Bafana A, Naoghare PK, Arrigo P, et al. Noncoding RNAs: Possible players in the development of fluorosis. Biomed Res Int 2015; 2015 : 274852.  Back to cited text no. 20
    
21.
Yuan JS, Reed A, Chen F, Stewart CN Jr. Statistical analysis of real-time PCR data. BMC Bioinformatics 2006; 7 : 85.  Back to cited text no. 21
    
22.
Hosmer DW, Lemeshow S. Applied Logistic Regression. 2nd ed. Hoboken (NJ): John Wiley & Sons, Inc.; 2000.  Back to cited text no. 22
    
23.
Kremen J, Dolinkova M, Krajickova J, Blaha J, Anderlova K, Lacinova Z, et al. Increased subcutaneous and epicardial adipose tissue production of proinflammatory cytokines in cardiac surgery patients: Possible role in postoperative insulin resistance. J Clin Endocrinol Metab 2006; 91 : 4620-7.  Back to cited text no. 23
    
24.
Cheng KH, Chu CS, Lee KT, Lin TH, Hsieh CC, Chiu CC, et al. Adipocytokines and proinflammatory mediators from abdominal and epicardial adipose tissue in patients with coronary artery disease. Int J Obes (Lond) 2008; 32 : 268-74.  Back to cited text no. 24
    
25.
Greif M, Becker A, von Ziegler F, Lebherz C, Lehrke M, Broedl UC, et al. Pericardial adipose tissue determined by dual source CT is a risk factor for coronary atherosclerosis. Arterioscler Thromb Vasc Biol 2009; 29 : 781-6.  Back to cited text no. 25
    
26.
Hirata Y, Tabata M, Kurobe H, Motoki T, Akaike M, Nishio C, et al. Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue. J Am Coll Cardiol 2011; 58 : 248-55.  Back to cited text no. 26
    
27.
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112 : 1821-30.  Back to cited text no. 27
    
28.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112 : 1796-808.  Back to cited text no. 28
    
29.
Verhagen SN, Vink A, van der Graaf Y, Visseren FL. Coronary perivascular adipose tissue characteristics are related to atherosclerotic plaque size and composition. A post-mortem study. Atherosclerosis 2012; 225 : 99-104.  Back to cited text no. 29
    
30.
Braunersreuther V, Mach F, Steffens S. The specific role of chemokines in atherosclerosis. Thromb Haemost 2007; 97 : 714-21.  Back to cited text no. 30
    
31.
Cherian S, Lopaschuk GD, Carvalho E. Cellular cross-talk between epicardial adipose tissue and myocardium in relation to the pathogenesis of cardiovascular disease. Am J Physiol Endocrinol Metab 2012; 303 : E937-49.  Back to cited text no. 31
    
32.
Miyata K, Shimokawa H, Kandabashi T, Higo T, Morishige K, Eto Y, et al. Rho-kinase is involved in macrophage-mediated formation of coronary vascular lesions in pigs in vivo. Arterioscler Thromb Vasc Biol 2000; 20 : 2351-8.  Back to cited text no. 32
    
33.
Vacca M, Di Eusanio M, Cariello M, Graziano G, D'Amore S, Petridis FD, et al. Integrative miRNA and whole-genome analyses of epicardial adipose tissue in patients with coronary atherosclerosis. Cardiovasc Res 2016; 109 : 228-39.  Back to cited text no. 33
    
34.
Mattu HS, Randeva HS. Role of adipokines in cardiovascular disease. J Endocrinol 2013; 216 : T17-36.  Back to cited text no. 34
    
35.
Iacobellis G, Singh N, Wharton S, Sharma AM. Substantial changes in epicardial fat thickness after weight loss in severely obese subjects. Obesity (Silver Spring) 2008; 16 : 1693-7.  Back to cited text no. 35
    
36.
Willens HJ, Byers P, Chirinos JA, Labrador E, Hare JM, de Marchena E. Effects of weight loss after bariatric surgery on epicardial fat measured using echocardiography. Am J Cardiol 2007; 99 : 1242-5.  Back to cited text no. 36
    
37.
Kim MK, Tomita T, Kim MJ, Sasai H, Maeda S, Tanaka K. Aerobic exercise training reduces epicardial fat in obese men. J Appl Physiol (1985) 2009; 106 : 5-11.  Back to cited text no. 37
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
    Material & M...
   Results
   Discussion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed462    
    Printed1    
    Emailed0    
    PDF Downloaded304    
    Comments [Add]    

Recommend this journal