Bone Morphogenetic Protein-2 and Osteopontin Gene Expression in Epicardial Adipose Tissue from Patients with Coronary Artery Disease Is Associated with the Presence of Calcified Atherosclerotic Plaques

María Luna-Luna; Sergio Criales-Vera; Diana Medina-Leyte; Mariana Díaz-Zamudio; Adriana Flores-Zapata; David Cruz-Robles; Mauricio López-Meneses; Sergio Olvera-Cruz; Samuel Ramírez-Marroquín; Cristóbal Flores-Castillo; José Manuel Fragoso; Elizabeth Carreón-Torres; Jesús Vargas-Barrón; Gilberto Vargas-Alarcón; Óscar Pérez-Méndez

doi:10.2147/DMSO.S253632

Bone Morphogenetic Protein-2 and Osteopontin Gene Expression in Epicardial Adipose Tissue from Patients with Coronary Artery Disease Is Associated with the Presence of Calcified Atherosclerotic Plaques

Diabetes Metab Syndr Obes. 2020 Jun 11:13:1943-1951. doi: 10.2147/DMSO.S253632. eCollection 2020.

Authors

María Luna-Luna¹, Sergio Criales-Vera², Diana Medina-Leyte¹, Mariana Díaz-Zamudio², Adriana Flores-Zapata¹, David Cruz-Robles¹, Mauricio López-Meneses³, Sergio Olvera-Cruz³, Samuel Ramírez-Marroquín⁴, Cristóbal Flores-Castillo¹, José Manuel Fragoso¹, Elizabeth Carreón-Torres¹, Jesús Vargas-Barrón⁵, Gilberto Vargas-Alarcón¹, Óscar Pérez-Méndez^{1

6}

Affiliations

¹ Molecular Biology, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
² Radiology, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
³ Adult Cardiology, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
⁴ Cardiothoracic Surgery, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
⁵ Research Direction, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
⁶ School of Engineering and Sciences, Tecnológico de Monterrey, Campus Monterrey, Mexico City, Mexico.

Abstract

Purpose: It has been proposed that the cardiovascular effects of obesity are related to epicardial adipose tissue (EAT), which seems to play an active role on the development and calcification of atherosclerotic plaques, but the mechanisms are still unknown. Therefore, the aim of this study was to determine whether the EAT expresses the genes of calcifying factors and whether such expression is associated with the body mass index (BMI) and with the presence of coronary artery calcium (CAC) in patients with coronary artery disease (CAD).

Patients and methods: Forty-three patients with CAD were enrolled specifically for this study, and their CAC score and EAT volume were determined by computed tomography. As the group of comparison, 41 patients with aortic valve stenosis and CAC = 0 were included (control group). A representative subgroup of 16 CAD patients and 23 controls were selected to obtain EAT biopsies during the chirurgical procedure from the atrio-interventricular groove. The mRNA expression of bone morphogenetic protein-2 and -4 (BMP-2, BMP-4), osteopontin (OPN), osteonectin (ON), and osteoprotegerin (OPG) in EAT was determined by qPCR.

Results: The gene expression of OPN and BMP-2 was 70% and 52% higher in the EAT from CAD patients than that in controls, respectively, whereas the expression of OPG, ON, and BMP-4 was similar in both groups. The EAT volume positively correlated with OPG and with the BMI, suggesting a relationship of obesity with local higher expression of calcifying genes in the coronary territory. The logistic regression analysis showed that high levels of both OPN and BMP-2 increased about 6 and 8 times the odds of coronary calcification (CAC score > 0), respectively.

Conclusion: EAT correlated with BMI and expressed the mRNA of calcifying genes but only OPN and BMP-2 expression was higher in CAD patients. Higher levels of both OPN and BMP-2 statistically determined the presence of calcium in coronary arteries of CAD patients.

Keywords: adipocyte; atherosclerosis; calcifying proteins; coronary artery disease; obesity.