The number and phenotype of myocardial and adipose tissue CD68+ cells is associated with cardiovascular and metabolic disease in heart surgery patients

Nutr Metab Cardiovasc Dis. 2019 Sep;29(9):946-955. doi: 10.1016/j.numecd.2019.05.063. Epub 2019 May 30.

Abstract

Background and aims: CD68+ cells are a potent source of inflammatory cytokines in adipose tissue and myocardium. The development of low-grade inflammation in adipose tissue is implicated in the pathogenesis of obesity-associated disorders including type 2 diabetes mellitus (T2DM) and cardiovascular disease. The main aim of the study was to characterize and quantify myocardial and adipose tissue CD68+ cells and adipose tissue crown-like structures (CLS) in patients with obesity, coronary artery disease (CAD) and T2DM.

Methods and results: Samples were obtained from the right atrium, epicardial (EAT) and subcutaneous adipose tissue (SAT) during elective heart surgery (non-obese, n = 34 patients; obese, n = 24 patients). Immunohistochemistry was used to visualize CD68+ cells. M1-polarized macrophages were visualized by immunohistochemical detection of CD11c. The proportion of CD68+ cells was higher in EAT than in SAT (43.4 ± 25.0 versus 32.5 ± 23.1 cells per 1 mm2; p = 0.015). Myocardial CD68+ cells were more abundant in obese patients (45.6 ± 24.5 versus 27.7 ± 14.8 cells per 1 mm2; p = 0.045). In SAT, CD68+ cells were more frequent in CAD patients (37.3 ± 23.0 versus 23.1 ± 20.9 cells per 1 mm2; p = 0.012). Patients having CLS in their SAT had higher average BMI (34.1 ± 6.4 versus 29.0 ± 4.5; p = 0.024).

Conclusions: Regional-based increases in the frequency of CD68+ cells and changes of their phenotype in CLS were detected in obese patients and CAD patients. Therapeutic modulation of adipose tissue inflammation may represent a target for treatment of obesity.

Keywords: Coronary artery disease; Crown-like structures; Epicardium; Macrophages; Myocardium; Obesity; Type 2 diabetes mellitus.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / analysis*
  • Antigens, Differentiation, Myelomonocytic / analysis*
  • Biomarkers / analysis
  • CD11c Antigen / analysis
  • Case-Control Studies
  • Cell Count
  • Coronary Artery Disease / immunology
  • Coronary Artery Disease / pathology*
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology*
  • Macrophages / immunology
  • Macrophages / pathology*
  • Male
  • Middle Aged
  • Myocardium / immunology
  • Myocardium / pathology*
  • Obesity / immunology
  • Obesity / pathology*
  • Phenotype
  • Subcutaneous Fat / immunology
  • Subcutaneous Fat / pathology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD11c Antigen
  • CD68 antigen, human