Macrophage Accumulation and Angiogenesis in Epicardial Adipose Tissue in Cardiac Patients with or without Chronic Heart Failure

Abstract

Routinely measuring epicardial fat had become a novel tool for cardiovascular risk stratification. Structural changes in epicardial adipose tissue (EAT), including fat thickness, inflammation, and angiogenesis, have been described in coronary artery disease (CAD) patients. We proposed to measure EAT thickness and characterize inflammatory infiltrate and angiogenesis in epicardial adipose tissue in CAD patients with and without chronic heart failure (CHF), established by cardiac dysfunction on echocardiography (left ventricular ejection fraction, LVEF ≤ 50%) and symptoms of heart failure (New York Heart Association (NYHA) functional class II or III).The study included 15 patients with CAD (demonstrated by coronary angiography),, who underwent right atrial appendages (RAA) excision during coronary artery bypass graft (CABG). The study was performed by histopathological, immunohistochemical (IHC), and morphometrical analysis. EAT thickness was assessed by using morphometry applied on routine histological stains. Inflammatory cell infiltration and angiogenesis were investigated immunohistochemically by using antibodies against CD68 and CD34 markers. Diminished EAT thickness in the CAD patients with CHF was associated with increased macrophage infiltration and reduced angiogenesis of the EAT as compared to CAD patients without CHF. In conclusion, the present study on epicardial fat samples of the RAA suggested that high expression of CD68 appeared to be associated with severe deterioration of heart function in CAD patients who underwent myocardial revascularization consisting of CABG.

Multiple roles of cardiac macrophages in heart homeostasis and failure

“…WGA, wheat germ agglutinin demarcates cell borders. Scale bar, 50 μm increases in the circulation [110], and macrophages accumulate in the adipose tissue, especially in the epicardial adipose tissue (EAT) [111][112][113]. There are studies suggesting that macrophages can participate in the process of adaptive thermogenesis by the production of catecholamines [114].…”

“…Obesity correlates with worse myocardial symptoms in patients with HF [ 108 ] and greater systemic and local inflammation [ 109 ]. The level of monocytes increases in the circulation [ 110 ], and macrophages accumulate in the adipose tissue, especially in the epicardial adipose tissue (EAT) [ 111 – 113 ]. There are studies suggesting that macrophages can participate in the process of adaptive thermogenesis by the production of catecholamines [ 114 ].…”

Browning Epicardial Adipose Tissue: Friend or Foe?

“…Two main hypotheses exist to explain how EAT-derived secreted molecules can interact with coronary arteries [20,21]. First, the paracrine signaling which assumes that EAT-derived adipokines diffuse directly through the layers (adventitia, media and intima) of the vascular wall via the interstitial fluid to interact with smooth muscle [17,22,23]. Then, the vasocrine signaling hypothesis, which implies that adipokines and FFAs directly enter into the vasa vasorum and are transported downstream into the arterial wall [20,24].…”

“…Remarkably, Hirata et al characterized the phenotype of macrophages and demonstrated that M1 macrophages are increased and M2 macrophages are decreased in EAT of CAD compared to non-CAD patients [45]. Recently, a study has also suggested that an elevated number of macrophages appeared to be associated with severe deterioration of heart function in CAD patients [23].…”

Causative Mechanisms of Childhood and Adolescent Obesity Leading to Adult Cardiometabolic Disease: A Literature Review

“…These mechanisms could help explain the association between increased epicardial adiposity and ischemic heart disease, heart failure, hypertension, left ventricular hypertrophy, dyslipidemia, and insulin resistance [48][49][50][51][52][53]. Local macrophage accumulation and angiogenesis within epicardial adipose tissue also seem to play an important part in the inflammatory-mediated mechanisms that link increased epicardial fat to worse outcomes in patients with coronary artery disease [54].…”