<p>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</p>

Abstract

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.

T Cell Immunosenescence in Aging, Obesity, and Cardiovascular Disease

“…In humans, OPN expression increases in the epicardial fat of patients with CAD compared to control subjects and is associated with the presence of calcified atherosclerotic plaques. [145] We have confirmed that senescent CD153 + PD-1 + CD44 hi CD 4+ T cells markedly increased and produced a large amount of OPN in the epicardial fat of HFD-induced obese mice (K. Shirakawa, unpublished observation). These findings suggest that senescent CD 4+ T cells in epicardial fat, at least in part, contribute to the development and worsening of CVD in obese patients.…”

“…Epicardial and pericardial fat are associated with cardiovascular risk [ 142 , 143 , 144 , 145 ]. In humans, OPN expression increases in the epicardial fat of patients with CAD compared to control subjects and is associated with the presence of calcified atherosclerotic plaques.…”

3D bioactive cell-free-scaffolds for in-vitro/in-vivo capture and directed osteoinduction of stem cells for bone tissue regeneration

“…It should be noted that PCL/PLGA-PEI scaffolds with sustaining BMP2 release had the best promoting effect on the in vitro differentiation of stem cells. Continuous BMP2 supply, whether free or from polyester loading, can upregulate the expression levels of molecular markers related to the bone differentiation, such as Runx2 [ 54 , 55 ], OPN [ 56 , 57 ], COL-1 [ 58 ] and OCN [ 59 ], as well as simultaneously downregulate the expression of BSP [ 60 ].…”

Matrix-GLA-Protein and Vascular Calcification: Can Diet Influence the Consequences of Matrix GLA Protein Inactivation? A Review

“…Fetuin-A itself may inhibit VSMC-related calcification via inhibition of apoptosis of VSMCs, promotion of clearance of apoptotic bodies released by VSMCs, and inhibition of intracellular mineralization of matrix vesicles of VSMCs [149][150][151][152][153][154][155] .…”